Beruflich Dokumente
Kultur Dokumente
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Editors
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Authors
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Notice
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Preface
Table of Contents
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1 - Introduction
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6 - Laboratory Diagnosis
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11 - Infective Endocarditis
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12 - Intra-abdominal Infections
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17 - Sepsis Syndrome
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20 - Infectious Diarrhea
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21 - Hepatobiliary Infections
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27 - Enteroviruses
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28 - Rhinoviruses
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29 - Influenza
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30 - Parainfluenza Virus
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32 - Adenoviruses
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33 - Herpesviruses
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34 - Measles
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35 - Mumps
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36 - Rubella
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37 - Rotavirus
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39 - Hepatitis
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41 - Poxviruses
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42 - Parvoviruses
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45 - Papovaviruses
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46 - Staphylococci
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47 - Streptococcus pneumoniae
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48 - Streptococcus pyogenes
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49 - Enterococci
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54 - Pseudomonas aeruginosa
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55 - Helicobacter pylori
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58 - Legionella
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59 - Important Anaerobes
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61 - Tuberculosis
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62 - Other Mycobacteria
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63 - Actinomycetes
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64 - Treponema pallidum
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67 - Chlamydia
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69 - Bartonella
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70 - Histoplasma capsulatum
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71 - Blastomyces dermatitidis
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72 - Coccidioides
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73 - Candida species
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74 - Cryptococcus neoformans
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76 - Sporothrix schenckii
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78 - Dermatophytes
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79 - Pneumocystis carinii
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A - Protozoa
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81 - Toxoplasma gondii
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82 - Pathogenic Amebas
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84 - Giardia
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B - Helminths
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86 - Nematodes
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87 - Cestodes
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88 - Trematodes
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89 - Infections in Travelers
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90 - Zoonotic Infections
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Back of Book
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Subject Index
2001
McGraw-Hill
Editors
Walter R. Wilson MD
Professor of Medicine
Mayo Medical School; Consultant, Mayo Clinic, Rochester
Merle A. Sande MD
Professor and Chairman
The Clarence M. and Ruth N. Birrer; Presidential Endowed Chair
in Internal Medicine, Department of Internal Medicine,
University of Utah, Salt Lake City
Associate
Editors
of
Secondary
Editors
Reinhardt
Editor
Isabel
Nogueira
Editor
Peter J. Boyle
Editor
Richard Ruzycka
Production
Supervisor
Charissa Baker
Art Manager
The illustrators were Laura Pardi Duprey and Teshin
Associates.
The index was prepared by Katherine Pitcoff.
R.R. Donnelley and Sons, Inc. was printer and binder.
Authors
Andrew D. Badley MD, FRCPC
Assistant Professor of Medicine
Division of Infectious Diseases, Ottawa Hospital; Clinician
Scientist, Ottawa Hospital Research Institute, Ottawa, Ontario,
Canada
Internet: abadley@ottawahospital.on.ca
Sepsis
Syndrome; Cestodes
Michael Bell MD
Post-Doctoral
Fellow
Division of Infectious Diseases, Department of Internal
Medicine, University of California, San Francisco; Assistant
Hospital
Epidemiologist,
San
Francisco
General
Hospital
Internet: zzb8@cdc.gov
Legionella
Elie F. Berbari MD
Fellow
Division of Infectious Diseases, Mayo Clinic, Rochester
Internet: berbari.elie@mayo.edu
Brucella,
Francisella,
Pasteurella,
Yersinia,
and
HACEK
Instructor
Department of Oncology, The Johns Hopkins University School
of Medicine, Baltimore
Internet: brahmju@jhmi.edu
Fever of Unknown Origin; Tuberculosis; Other
Mycobacteria
James J. Chamberlain MD
Former Chief Medical Resident
Department of Internal Medicine, University of Utah, Salt Lake
City; Medalia Medical Group, North Everett Internal Medicine,
Everett,
Washington
Internet: jimchammd@yahoo.com
Cryptococcus; Pneumocystis
Carinii
Sandra V. Chaparro MD
Postdoctoral Fellow
Division of Infectious Diseases, Stanford University
Internet: sandra@molepi.stanford.edu
Borrelia & Leptospira Species
William P. Ciesla Jr. MD
Assistant Professor of Research
Division of Geographic and International Medicine, University of
Virginia School of Medicine, Charlottesville
Internet: wpc6n@virginia.edu
Infectious
Diarrhea
Internet: cockerill.franklin@mayo.edu
Laboratory
Diagnosis; Laboratory Diagnosis: Diagnosis of
Bacterial, Fungal, & Parasitic Infections; Enteritis Caused by
Escherichia coli & Shigella & Salmonella Species; Vibrio &
Campylobacter
Lisa Danzig MD
Assistant Clinical Professor of Medicine
University of California, San Francisco; Director, Clinical
Development, Chiron Corporation, Emeryville, California
Internet: lisa_danzig@chiron.com
Influenza
David H. Dockrell MD, MRCPI
Instructor in Medicine
Mayo Graduate School of Medicine; Fellow in Infectious
Diseases, Mayo Clinic, Rochester
Internet: d.h.dockrell@sheffield.ac.uk
Patients With Neutropenia & Fever; Pseudomonas
Aeruginosa
Marlene L. Durand MD
Assistant Professor of Medicine
Harvard Medical School; Director, Infectious Disease Service,
Massachusetts Eye & Ear Infirmary; and Assistant Physician,
Massachusetts General Hospital, Boston
Internet: marlene_durand@meei.harvard.edu
Infections of the Eye & Orbit
Paul B. Eckburg MD
Fellow in Infectious Diseases
Stanford University School of Medicine
Internet: paul_eckburg@hotmail.com
Hepatobiliary
Infections
Disease
Consultant
Internet: edson.randall@mayo.edu
Skin & Soft-Tissue Infections
Christopher R. Fox MD
Clinical Fellow
Division of Endocrinology and Metabolism, University of Virginia,
Charlottesville
Internet: crf2f@virginia.edu
Candida
Species; Pathogenic
Amebas
Influenza
Julie Louise Gerberding MD, MPH
Associate Professor of Medicine (Infectious Diseases)
San Francisco General Hospital, University of California, San
Francisco
Infection
Prevention
in
Healthcare
Donald L. Granger MD
Professor of Internal Medicine
Division of Infectious Diseases, University of Utah School of
Medicine, Salt Lake City
Internet: dgranger@hsc.utah.edu
Basic Principles of Host Defense; Cryptococcus
Richard L. Guerrant MD
Professor
Department of Internal Medicine and Head, Division of
Geographic Medicine, University of Virginia School of Medicine,
Charlottesville
Internet: rlg9a@virginia.edu
Infectious
Diarrhea
Devon C. Hale MD
Professor of Medicine and Pathology; Director of International
Travel Clinic
University of Utah School of Medicine, Salt Lake City
Internet: devon.hale@hsc.utah.edu
Cryptosporidium, Cyclospora, & Isospora Species &
Microsporidia; Giardia; Infections in Travelers
Nancy K. Henry PhD, MD
Associate Professor of Pediatrics
Syncytial
Virus; Measles;
Harry R. Hill MD
Professor of Pathology, Pediatrics, and Medicine
University of Utah School of Medicine, Salt Lake City
Internet: harry.hill@path.med.utah.edu
Patients With Recurrent Infections and Leukocyte Abnormalities
Yenjean Syn Hwang MD
Department of Medicine, Alta Bates Medical Center, Berkeley
Internet: yshwang@pol.net
Obstetric
&
Gynecologic
Infections; Other
Mycobacteria
Michael R. Keating MD
Assistant Professor of Medicine and Consultant
Infectious Diseases and Internal Medicine, Mayo Clinic,
Rochester
Internet: keating.michael@mayo.edu
Aspergillus, Pseudallescheria, & Agents of Mucormycosis;
Fusarium, Penicillium, Paracoccidioides, & Agents of
Chromomycosis
Timothy R. Laine MD
Adjunct Clinical Assistant Professor
Department of Pathology, Division of Clinical Immunology,
University of Utah Medical Center, Salt Lake City
Pallidum
Mountain
View,
California
Internet: jloutit@intrabiotics.com
Intra-Abdominal
Infections; Gram-Positive
Aerobic
Bacilli;
Coxiella,
Ehrlichia,
&
Rickettsia; Bartonella
Medicine,
University
of
Internet: martin@psg.ucsf.edu
Streptococcus
Pneumoniae
Zell A. McGee MD
Professor of Medicine and Pathology, and Director
Center for Infectious Diseases, University of Utah School of
Medicine, Salt Lake City
Internet: zell.mcgee@hsc.utah.edu
Infections of the Central Nervous System
Caroline K. Milne MD
General Medicine Fellow
Division of General Medicine, University of Pennsylvania School
of Medicine, Philadelphia
Internet: milnec@mail.med.upenn.edu
Coccidioides; Infections
in
Travelers
Jose G. Montoya MD
Assistant Professor of Medicine
Department of Medicine and Division of Infectious Diseases and
Geographic Medicine, Stanford University School of Medicine;
Attending Physician, Stanford University Medical Center; Adjunct
Associate Staff Scientist, Department of Immunology and
Infectious Diseases, Palo Alto Medical Foundation Research
Institute,
California
Internet: gilberto@leland.stanford.edu
Hepatobiliary
Mycoplasma
&
Gondii
Prevention
in
Healthcare
Settings
Douglas R. Osmon MD
Assistant Professor of Medicine, and Consultant in Infectious
Diseases
Division of Infectious Diseases, Mayo Clinic, Mayo Foundation,
Rochester
Internet: osmon.douglas@mayo.edu
Osteomyelitis,
Infectious
Arthritis
&
Prosthetic-Joint
Infection
Infectious
Gram-
Disease
Internet: persing@corixa.com
Malaria & Babesia
Gary W. Procop MD, MS
Section Head
Clinical
Microbiology,
Cleveland
Clinic
Foundation
Internet: procopg@ccf.org
Enteritis Caused by Escherichia coli & Shigella & Salmonella
Species; Vibrio
&
David A. Relman MD
Associate Professor of Medicine
Microbiology & Immunology, Departments of Medicine,
Microbiology & Immunology, Stanford University School of
Medicine; Physician, Veterans Affairs Palo Alto Health Care
System, Palo Alto, California
Internet: relman@cmgm.stanford.edu
Basic Principles of Microbial Virulence; Gram-Positive
Aerobic
Prevention
in
Healthcare
Settings
Kristen Ries MD
Professor of Medicine; Director of AIDS Clinical Services
University of Utah School of Medicine, Salt Lake City
Internet: kristen.ries@hsc.utah.edu
Pneumocystis
Carinii
Bordetella,
&
Branhamella
Species
Merle A. Sande MD
Professor and Chairman
The Clarence M. and Ruth N. Birrer Presidential Endowed Chair
in Internal Medicine, Department of Internal Medicine,
University of Utah, Salt Lake City
Internet: merle.sande@med.utah.edu
Introduction; Fever of Unknown Origin; Fever & Rash; Obstetric
& Gynecologic Infections; Patients With AIDS; Tuberculosis;
Other Mycobacteria; Coccidioides; Candida Species; Pathogenic
Amebas
Javeed Siddiqui MD, MPH
Fellow
Division of Infectious Diseases, University of California, Davis
Medical Center, Sacramento
Internet: jsmdmph@yahoo.com
Helicobacter
Pylori
Stephanie B. Silas MD
Rheumatology Fellow
Department of Internal Medicine, University of Utah Health
Sciences Center, Salt Lake City
Internet: stephanie.silas@hsc.utah.edu
Cryptosporidium, Cyclospora, & Isospora Species &
Microsporidia; Giardia
D. Scott Smith MD, SM, DTM & T
Clinical Instructor (VCF)
Stanford Medical School, Stanford, California; Chief, Infectious
Disease and Geographic Medicine, Kaiser Permanente Hospital,
Redwood
City,
California
Internet: darvin.s.smith@kp.org
Neisseria Gonorrhoeae & Neisseria Meningitidis; Dermatophytes;
Leishmania & Trypanosoma; Zoonotic
Infections
Jay V. Solnick MD, PhD
Assistant
Professor
Department of Internal Medicine, Division of Infectious &
Immunologic Diseases, University of California, Davis Medical
Center, Sacramento
Internet: jvsolnick@ucdavis.edu
Helicobacter
Pylori
Syncytial
Virus; Measles;
James M. Steckelberg MD
Professor of Medicine
Mayo Medical School; Chair, Division of Infectious Diseases,
Mayo Clinic and Foundation, Rochester
Infective
Endocarditis; Osteomyelitis,
Infectious
Arthritis
&
Prosthetic-Joint
Infection; Sepsis Syndrome; Important
Anaerobes; Nematodes; Cestodes; Trematodes; Ectoparasitic
Infestations & Arthropod Stings & Bites
Dennis L. Stevens MD, PhD
Professor of Medicine
University of Washington School of Medicine, Seattle; Chief,
Infectious Diseases Section, Veterans Affairs Medical Center,
Boise
Internet: dlsteven@primenet.com
Streptococcus
Pyogenes
Zelalem Temesgen MD
Assistant Professor of Medicine
Mayo Medical School; Consultant, Division of Infectious
Diseases, and Director, HIV Clinic, Mayo Clinic, Rochester
Internet: temesgen.zelalem@mayo.edu
Histoplasma
Schenckii
Capsulatum; Blastomyces
Dermatitidis; Sporothrix
Anaerobes
Rochester
Internet: virka@mayo.edu
Upper Respiratory Tract Infections; Tracheobronchitis
Respiratory Tract Infections
&
Lower
Transmitted
Diseases
Walter R. Wilson MD
Professor of Medicine
Mayo Medical School; Consultant, Mayo Clinic, Rochester
General Principles of Antimicrobial Therapy; Tracheobronchitis
&
Lower Respiratory Tract Infections; Infective
Endocarditis;
Urinary Tract Infections; Pseudomonas
Aeruginosa; Brucella,
Francisella, Pasteurella, Yersinia, and HACEK; Nematodes;
Cestodes; Trematodes; Ectoparasitic Infestations & Arthropod
Stings & Bites
Dani-Margot
Fellow
Zavasky
MD
2001
McGraw-Hill
Preface
Current Diagnosis & Treatment in Infectious Diseases is a
one-stop source of essential, clinically oriented
information on infectious diseases for students, house officers,
practitioners, and other health care providers in both hospital
and ambulatory settings. CDTID covers all infectious disease
topics of concern to primary care physicians, infectious disease
specialists, and other specialists who provide preventative,
diagnostic, or therapeutic care for patients with infectious
diseases. It stresses the practical features of clinical diagnosis
and patient management.
OUTSTANDING
FEATURES
INTENDED
AUDIENCE
text.
ACKNOWLEDGMENTS
We wish to thank our contributing authors for their time and
hard work involved in preparing this text. We wish to thank the
editors of McGraw-Hill and their staff for their valuable
assistance and support. We welcome comments and
2001
McGraw-Hill
1
Introduction
Merle A. Sande MD
As a leading cause of death worldwide, infectious diseases have
hardly been conquered or controlled. In fact, one might consider
the 1990s as an era of reawakening, when new and reemerging
infectious diseases were recognized as a major worldwide health
problem. The continued explosion of cases of infections caused
by the human immunodeficiency virus has now produced
negative population growth and major disruption in the societies
of many African countries, where more than 35% of young
adults are infected and more than 25% of children are orphans.
By the end of the millennium, the virus had infected more than
50 million people; it now ranks with childhood diarrheal
diseases, pneumonia, malaria, and tuberculosis as a leading
cause of death. While highly active antiretroviral therapy
(HAART) has been astonishingly effective in treating the
disease, the necessary drugs are available to only a small
percentage of infected populations, and transmission of the
virus continues unabated in many regions of the world.
The ability of modern technology to control infectious diseases
has been found lacking. Antibiotics, which were developed
within the last 60 years, resulted in the cure of many previously
lethal infections, rightfully earning the name wonder
There
seems
P.2
readied it for use against the West, along with anthrax spores,
Yersinia pestis, and other organisms. The human potential for
destructive acts seems limitless.
Other infectious diseases have also slipped back into our
society. Our attempts to control mosquitoes were initially
successful, and federally funded programs reduced the Aedes
aegypti and Anopheles species to the point where the
arthropod-borne encephalitis viruses almost disappeared.
Malaria, once the scourge of the southern United States and
Central America, was nearly eliminated. However, while these
mosquitoes became resistant to DDT, apathy dominated the
governments' response, and funding was cut. The mosquitoes
have returned en masse, as have dengue, yellow fever, diseases
induced by the various encephalitis viruses, and malaria.
Finally, cholera, which had disappeared from the Western
Hemisphere for decades, reappeared in Peru in the early 1990s
and spread throughout Central and South America, wherever
poor sanitation and poverty dominate the domestic scene.
Within several years, over a million cases and thousands of
deaths were reported, another reminder of the fragile control
we have on infectious diseases.
When the public health infrastructure of our cities is allowed to
deteriorate, microbial pathogens are ready and willing to take
advantage of our citizens. In New York City in the late 1980s,
funding for the tuberculosis program, among many others, was
reduced and case follow-up was discontinued; the follow-up rate
for patients discharged from hospitals with a diagnosis of active
tuberculosis was approximately 10%. Partly because of poor
patient compliance with therapy, multiple-drug-resistant
tuberculosis emerged and began to spread to other parts of the
country. Many people, especially AIDS patients, died before the
epidemic was finally controlled, when directly observed therapy
was widely embraced and implemented. Similarly, when
immunization slackened in Eastern Europe after the fall of
communism, diphtheria reappeared, and more than 50,000
cases per year were reported in the early 1990s.
2001
McGraw-Hill
2
Basic Principles of Host Defense
Donald L. Granger MD
Higher animals have evolved many host defense mechanisms that ensure
the relatively long-term survival of individuals despite their coexistence
with countless microorganisms. Healthy people are at equilibrium with the
microbial world; their internal soma, rich in nutrients, remains free of
replicating microorganisms. Disease can be viewed as progression away
from this equilibrium, in which microorganisms invade the body from the
environment and replicate, causing inflammation and destruction of the
tissues, as well as depletion of the host's nutrients. Unchecked, the rapid
expansion of the microbial population leads to the death of the host.
A similar but distinct scenario is that the internal environment contains a
variety of viruses, bacteria, fungi, protozoa, and microscopic metazoa,
which are acquired throughout life. Again, these organisms achieve
equilibrium with the mammalian host. Under these conditions they do not
replicate, nor do they produce toxins. Instead, they exist in a dormant or
latent state, which is infection without disease. Disease is a progression
away from the equilibrium. When the balance is disturbed, microbial
replication begins; host nutrients are then consumed by the proliferating
population of microorganisms. This process leads to disease and ultimately
death unless microbial replication is blocked.
To maintain equilibrium with the microbial worldthat is, to maintain a
distinct
functions.
The first form includes the antimicrobial defense mechanisms that have
evolved throughout the vertebrate species. Specifically, this first form is
composed of a variety of mechanisms to prevent invasion of sterile tissues
from contiguous body sites that are teeming with microbial flora. These
mechanisms involve the actions of specialized cellsphagocytes and
lymphocytes. For example, the upper respiratory tract is colonized with
large numbers of bacteria, yet further down into the respiratory tract,
below the vocal cords and into the lungs, few or no bacteria are found.
Those bacteria that do gain access to the lung are rapidly destroyed. In
another example, microbes may gain entrance to sterile body sites when an
open injury introduces bacteria into the skin, subcutaneous tissue, muscle,
or bone. This is countered by mechanisms in which the injured tissue is
walled off to prevent spread and is invaded by phagocytic cells that
envelop and kill bacteria. This is bactericidal activity. Yet another example
involves specialized microorganisms that have evolved into successful
parasites and that gain ready access to sterile sites in the host. They may
be highly resistant to host-killing mechanisms. Under these conditions,
equilibrium between parasite and host is reached by establishing
microbiostasis in the tissues. In this way, living microbes may remain
dormant or latent within host tissues for years, or even decades. This
scenario implies microbiostatic host-defense mechanisms. For example, the
human tubercle bacillus (Mycobacterium
tuberculosis ) is inhaled into the
lung. In the immunocompetent host, immunity is acquired, microbial
replication ceases, and the mycobacteria become dormant, especially (but
not exclusively) in the lung apices.
A second way to thwart infectious disease is through a set of uniquely
human prevention schemes that have resulted from brain development and
intelligence. Our understanding of infectious disease transmission has led
to effective prevention methods, such as the addition of chlorine to the
water supply and modern sewage treatment. Knowledge of immunology has
led to vaccine strategies that have achieved results such as the elimination
of smallpox from the human population. Understanding microbial
physiology and metabolism led to the discovery of antibiotics for treating
heretofore lethal infections.
INNATE
HOST
DEFENSES
DEFENSE MECHANISMS
PHYSIOLOGIC
LEVEL
AT
THE
Normal
Microbial
Flora
Site
Examples of Predominant
Microorganisms at These
Sites
Conditions of
Invasion
Disease
Potential
Anatomic
&
Physiologic
Factors
compounds.
Host
Nutritional
Status
The nutritional status of the host ranks as a critical factor for both innate
and acquired resistance to infection. Protein-calorie malnutrition in children
is associated with severe measles (rubeola virus). Historical observations
point to reactivation of dormant tubercle bacilli during acute food shortage
in populations with a high prevalence of this pathogen. Pyogenic bacterial
infections and periodontal disease are additional examples. The original
description of Pneumocystis
carinii as a human pathogen was based on
observations of pulmonary disease in starving European infants during and
after World War II. Experimental research shows that starvation impairs
phagocytes and cell-mediated immunity (CMI) before its effects on
antibody
production
Hormonal
are
observed.
Influences
Aging
Aging affects many aspects of innate defenses. Consequently, pneumonia,
urinary tract infections, cholecystitis, diverticulitis, and bacteremia caused
by pyogenic bacteria are increased. The aged are more likely to reactivate
latent organisms such as Herpes zoster virus and Mycobacterium
tuberculosis , which suggests decreased CMI. Aged individuals have
reduced ability to mount immunoglobulin (Ig) synthesis against
polysaccharide
antigens.
The
Acute-Phase
Response
AT
THE
Ever-present cells and molecules (constitutive mechanisms) form an onthe-spot defensive line against microbial invasion. Compromise of this
innate multifaceted system results in predictable serious infections, usually
with invading species of the microflora. Thus, the importance of
constitutive nonspecific defense mechanisms is revealed. Phagocytes and
natural killer (NK) cells are discussed as examples of innate cellular
defenses.
Phagocytes
Two types of cells can be considered professional phagocytes or
cells that consume microbes. These are the polymorphonuclear leukocytes
(called neutrophils, or granulocytes) and the MNPs (monocytes and
macrophages). These cells emanate from bone marrow precursors and
enter the circulation to perform their antimicrobial functions. Lack of either
of these cell lineages is incompatible with life.
Neutrophils live for 14 days after entering the circulation. Continued
neutrophil production is essential for survival. Neutrophils are an important
regulator of homeostasis between the body, which harbors sterile enclaves,
and the microbial world. Neutrophils deal with pyogenic bacteria and fungi.
Neutrophils possess tightly regulated microbicidal systems that
P.6
are activated within seconds after encountering microorganisms. In healthy
individuals, neutrophils are constantly at work destroying small numbers of
microbes that enter the body by various routes. Severe neutropenia (< 500
cells/L of blood) leads to overwhelming bacteremia from enteric bacilli.
Neutrophils are constitutively bactericidal to a high degree for grampositive and gram-negative cocci and enteric bacilli. To maintain this
constitutive defense, neutrophils have special functional properties, to be
discussed below. A defect in any one of these important functions
invariably leads to a life-threatening infection. However, neutrophils have
less or little activity against facultative or obligate intracellular pathogens
such as mycobacteria, dimorphic fungi, and protozoans. The human
immune system has evolved other mechanisms for dealing with these
pathogens.
Hypothalamus
Fever via prostaglandin synthesis
Postulated effect is inhibitory to microbial replication
Brain
Somnolence, release of endorphins
Sleep with muscle rest may be adaptive response
Pituitary gland
ACTH, TSH release
Adrenocorticosteroids adapt body to stress
to
inflammation
Liver
Decreased albumin synthesis; increased synthesis of acute-phase proteins
(fibrinogen, complement proteins, amyloid A protein, ceruloplasmin, Creactive protein, LPS-binding protein, proteinase inhibitors, fibronectin,
haptoglobin
Generalized metabolic adaptation to infection; nonspecific opsonins;
effects of tissue destruction caused by inflammation
Skeletal muscle
Proteolysisrelease of free amino acids to the circulatory system
mollify
expression
Effect
Produced
TSH,
immune
thyroid-
microbes from the circulation. Thus, the spleen serves as a highly efficient,
specialized RES site for removal of virulent bacteria. These bacteria avoid
clearance in other RES sites, such as the lung or liver, because they
possess virulence factors that have extraordinary antiphagocytic
properties, such as particular serotypes of exopolysaccharide capsules.
Individuals with no spleen may succumb to high-grade infection caused by
bacteria that possess antiphagocytic capsules. The alveolar spaces of the
lung are inhabited by macrophages, which form a first-line defense of the
lung. These cells phagocytize and kill inhaled viruses, bacteria, and fungi.
Macrophages and macrophage-like cells (eg, dendritic cells) contribute to
the adaptive immune response. Macrophages, which function in concert
with T lymphocytes, are responsible for CMI defense against intracellular
pathogens. Macrophages process and present antigen to lymphocytes and
receive activating signals during the immune response. These
signals enable the macrophages to control the replication of intracellular
microorganisms; they are also capable of killing these microorganisms (see
below). Some of the functions listed in Table 2-3 for neutrophils are also
relevant for MNPs.
To kill bacteria and fungi, phagocytes must make physical contact with
them. This involves a coordinated sequence of regulated
production, (2) release into the circulation, (3) attraction
infection, (4) adherence onto and translocation through
adjacent capillary walls, (5) chemotaxis, (6) attachment
events: (1)
to a site of
(diapedesis)
to and
infections
Release
Bone marrow, circulation
Increased cell numbers during active infections
Neutropenia leads to life-threatening
3
Chemokinesis
Focus of infected tissue
pyogenic
infections
interaction
Engulfment of microorganisms
Opsonins are molecules that bind microbes to phagocytes and initiate
engulfment
7
Microbicidal
activity
Phagolysosome of phagocyte
Killing
Genetic defects result in decreased resistance to infections
8
Digestion
Vacuolar system of phagocyte
Eliminate microbial products
Lysosomal enzyme systems
Stage
Function
Site
Required
for
Correlates of
Pathophysiology
inflammatory
site.
P.8
P.9
Chemotaxis (Stage 5). Phagocytes seek pathogens by attraction to
gradients of microbial products and signals generated by the host
inflammatory response. Motility of neutrophils increases in response to
environmental signals called chemotaxins, which include cytokines [IL6, IL-8, granulocyte macrophage CSF, tumor necrosis factor
(TNF), interferon- (IFN-)], leukotrienes, and chemical products
from microorganisms themselves (eg, microbial oligopeptides such as
formylmethionine-leucine-phenylalanine).
When
no
concentration
gradient is present, increased motility is random [chemokinesis (Figure
2-1E )]; however, in the presence of even weak gradients, neutrophil
motility becomes directed toward an increased concentration of
stimulus [chemotaxis (Figure 2-1F )]. The interaction between
chemotaxins, their high-affinity receptors on the neutrophil surface,
and cytoplasmic cytoskeletal events, which propel the cell forward, are
not entirely worked out. However, it is important that phagocyte
motility depends on a substrate upon which the phagocytes crawl.
These cells cannot swim. Thus it becomes clear that whenever bacteria
gain access to nutrient-rich fluid-filled spaces (eg, cerebrospinal,
pleural, peritoneal, pericardial, or synovial fluid), phagocyte defenses
are put at considerable disadvantage. Neutrophils must make physical
contact with the bacteria they kill. In a fluid-filled space (eg, massive
ascites), this contact depends on random collisions between bacterial
and phagocytic cells. Indeed, in the preantibiotic era, pyogenic
infections of fluid-filled
bacteremia is often a
or septic arthritis, one
from the bloodstream,
spaces. Bacteria that most often cause these infections are notoriously
difficult to clear from the bloodstream because they possess
antiphagocytic factors, most often capsules (S pneumoniae,
Streptococcus pyogenes, Neisseria meningitidis , and Haemophilus
influenzae ).
Phagocytosis (Stage 6). Phagocytosis is required to kill invading
microorganisms. Phagocytosis is a two-step process: (1) attachment of
the particle to the phagocyte occurs and (2) the phagocyte extends
lamellipodia circumferentially around the particle to enclose it within a
phagocytic vacuole called the phagosome (Figure 2-1G ). As noted
above, opsonic proteins (Igs and complement proteins) coat
microorganisms and, by engaging their receptors on the surface of
phagocytes, they mediate attachment. These receptor-ligand
interactions also induce intracellular events, which activate the
engulfment process. Engulfment itself is a highly energy-dependent
process and is powered by an ATP-dependent cytoskeletal
polymerization-depolymerization of actin microfilaments. Nonopsonic
Natural
Killer
Cells
NK cells are non-B, non-T lymphocytes that circulate in blood and function
in constitutive host defense by identifying and destroying cells infected
with viruses. Equipped with specialized proteins and enzymes packaged
within intracellular granules, NK cells lyse virus-infected host cells and
thereby interfere with viral replication. NK cells can bind yeast cells and
destroy them. NK cells are an important source of cytokines, chemical
messenger molecules that regulate the immune response. In rapidly
developing infections, NK cell-derived IFN- (one of the most important
cytokines) activates macrophages to a microbicidal state.
Further in the complement cascade, C5 is cleaved into large C5b and small
C5a proteolytic fragments.
P.11
C5a diffuses from the site of inflammation, which sets up a concentration
gradient that directs phagocyte emigration by chemotaxis.
Still later in the cascade a complex forms composed of C7, C8, and
C9the membrane attack complex (MAC). The MAC inserts itself into the
outer lipid bilayers of gram-negative bacteria-forming pores visible by
electron microscopy; this drastic perturbation leads to bacteriolysis.
Bacteriolysis effected by the MAC is thus a mechanism for killing bacteria
by fluid phase componentsa phagocyte is not directly involved.
However, bacteriolysis has limitations. First, gram-negative bacteria spawn
mutants that are resistant to the lysing capability of the MAC. Second,
gram-positive bacteria, mycobacteria, and fungi are naturally resistant to
the MAC. Although protozoa may be killed by the MAC, CMI is the main
defense mechanism against these pathogens.
The complement system performs three important host-defense functions:
(1) it generates C3b, a major opsonic component that promotes
phagocytosis; (2) it generates C5a, a chemotaxin that directs phagocyte
motility toward an inflammatory stimulus; and (3) it kills some gramnegative bacteria through the MAC.
Humans with complement deficiencies, although uncommon, have been
identified. These individuals exhibit characteristic susceptibilities to
infection, such as disseminated infection with Neisseria
gonorrhoeae.
ADAPTIVE
IMMUNE
meningitidis and N
RESPONSES
There are two general categories of adaptive immune responses. The first
comprises the synthesis of specific Ig proteins (antibodies) by specialized
lymphocytes called plasma cells. This is called humoral immunity. The
second type of response, CMI, involves direct or indirect attack on
microorganisms mediated by lymphocytes and other accessory cells (eg,
macrophages). Both humoral immunity and CMI are characterized by two
important features. First, the responses are directed toward specific
biochemical moieties on microorganisms, called antigens. Second, the
HUMORAL
Production
IMMUNITY
of
Antibodies
Immunoglobulin
Structure
All Igs share the same basic molecular structure. This structure consists of
two identical peptide heterodimers linked by disulfide bridges. Each
heterodimer consists of a heavy chain (CH ) and a light chain (CL ) (Figure
2-2 ).
The antigen-binding site is in the Fab portion. Three hypervariable regions
containing 1012 amino acids with markedly viable sequences occupy the
V K and VH domains. The quaternary structure of the CL and CH in this
region determines antigen specificity. Because each Ig molecule has two
heavy and two light chains, antibodies are bivalent for antigen binding. The
portion of the antigen recognized is called
P.12
the epitope. The complementary Fab-binding site is called the paratope.
Immunoglobulins
in
Humans
Five Ig classes defined by their CH type are present in humans (Table 2-4
). There are four IgG and two IgA subclasses. There are two classes of CL s
( and ). Each B lymphocyte produces only one class of CL .
Molecular weight
<150,000>
<400,000>
<900,000>
<180,000>
<190,000>
Serum concentration (mg/dl)
6001600
60330
45150
Trace
Trace
Half-life (days)
23
6
5
3
2
Complement
activation
2+
0
4+
0
0
Opsonic
activity1
4+
2+
0
0
0
Reaginic
0
0
0
activity
0
4+
Acts as B-cell receptor
+
4+
4+
Characteristic
IgG
Monomer
IgA
Dimer
IgM
Pentamer
IgD
Monomer
IgE
Monomer
reactions
against
certain
trematodes.
B Cells
Generation of an effective humoral immune response is vested in
progenitor cells located in the bone marrow, which undergo differentiation
to become mature B cells in the spleen and lymph nodes. Activation of
mature B cells into antibody-producing plasma cells is a complex, highly
regulated process. Regulation occurs through the expression of B-cell
surface receptor molecules, which alter cell function upon binding ligand.
Important B-cell receptors and their functions are shown in Table 2-5 .
Antigen binding to its specific receptor on B cells leads to the formation of
the B-cell receptor complex. When formed, the complex lowers the
threshold for B-cell activation. Intracellular signal transduction through
protein phosphorylation by Src kinases activates membrane phospholipase
C 2. Inositol triphosphate and diacylglycerol are formed. Intracellular
calcium is mobilized and protein kinase C is activated. Transcription of
cellular genes is induced by regulating cell division, differentiation, and Ig
synthesis. However, these events are usually not sufficient for high-level
antibody production. T cells, which recognize processed antigen-derived
peptide in association with complementary major histocompatibility
complex (MHC) class-II determinants, physically aggregate with B cells and
promote B-cell activation. This is called T-cell helper function. This is the
main pathway for antibody production against protein antigens.
B-cell receptor complex (IgM, IgD, CD19, CD21)
Antigen-specific receptor; triggers cell activation and endocytosis of bound
antigen
MHC II, B7, CD72, ICAM
Major histocompatibility complex class II molecule. Presents antigenic
peptide to complementary T-cell receptor. Engage T-cell receptorsto
promote T-cell-dependent B-cell activation.
Cytokine receptors
Transduce signals required for proliferation, activation, and differentiation
CD32 Fc low-affinity receptor
Down-regulates
immunoglobulin
production
1 Abbreviations: Ig, immunoglobulin; MHC, major histocompatibility
complex;
ICAM,
Receptor
intercellular
Molecules
adhesion
molecule.
Function
polymeric
antigens,
especially
bacterial
polysaccharides
bearing
Antibody
Diversity
of
P.14
Immunoglobulin
Fc
Receptors
Function
of
Antibody-Mediated
Host
Defense
mechanisms. The
mechanisms.
following
sections
summarize
antibody-directed
immune
IgG Fc receptors
RI (CD64) (high affinity)
Monocytes,
neutrophils
Phagocytosis; degranulation; ADCC
RII (CD32) (low affinity)
Monocytes, neutrophils, eosinophils, B
cells,
platelets
scavenge
immune
cellular
Function
of
endotoxemia.
CELL-MEDIATED
IMMUNITY
Cell-Cell
Interactions
Designation
Examples
Function
Cytokines
Cytokines function as chemical messengers, sending signals from one
immune cell to another. Cytokines are glycoprotein molecules secreted by
lymphocytes. These molecules were originally called lymphokines. As their
identities and cells of origin were defined, the term lymphokine was
replaced by cytokine to include signal molecules elaborated during CMI
whose cells of origin included other cell types (eg, macrophages,
endothelial cells, and fibroblasts). As cytokines became characterized
molecularly through cloning, sequencing, and expression techniques, they
were assigned numbers and designated as interleukins (Table 2-7 ).
However, some cytokines retained their original names, based primarily on
their immunologic activities (eg, IFNs, TNFs, and CSFs). During CMI,
cytokines act locally, infiltrating tissue sites of inflammatory cells.
However, they may exert systemic effects when released into the
circulation. This occurs during widespread infection and certain toxemias
tuberculosis
MNP
CD4+
CD8+
IFN-
TNF
TH 1
Fungi
Cryptococcus
CD4+
neoformans
NK
CD8+
MNP
IFN-
TH 1
Protozoa
Leishmania
CD4+
major
MNP
TNF
IL-12
IFN-
TH 1
Metazoa
Schistosoma mansoni
CD4+
MNP
IFN-
TH 1
Viruses
Cytomegalovirus
CD8*
IFN-
TH 1
1
Example
Effector
Cells
Cytokines
CMI
response
Activation
of
Effector
Cells
CD158+ lymphocytes
neoplastic cells and
that does not involve
against virus-infected
Category
Functions
and
Mediators
REFERENCES
Joklik WK, et al (editors): Zinsser
Lange, 1992.
Immunology.
Lippincott-Raven,
1999.
2001
McGraw-Hill
of
Microbial
Virulence
3
Basic Principles of Microbial
Virulence
David A. Relman MD
Among the vast diversity of microscopic life on this planet, only a
small subset is believed to be capable of infecting the human
body and causing disease. For example, only 7 of the 3840
extant bacterial divisions on the earth contain members that are
recognized pathogens in humans. The features that distinguish
this subset of microbes (bacteria, fungi, parasites, and viruses)
from all others have been revealed in increasing detail over the
past few decades through the development of methods in
microbial genetic manipulation, host cell imaging, structural
biology, and, more recently, genomics. The findings indicate
adaptation and coevolution of host and pathogen. Common
themes are apparent among the strategies and mechanisms used
by some microbes in their behavior as pathogens; these themes
are the focus of this chapter. From an evolutionary perspective,
pathogenicity appears to have arisen on multiple
occasions, among diverse putative microbial ancestors. The
commonality of themes and strategies that we witness today in
extant pathogens probably reflects convergent evolutionary
processes, operating in part over long periods of time, as host
MICROORGANISMS
AS
PATHOGENS
Staphylococcus
aureus
Encoded on bacteriophages
SopE (type III secreted effector)
Salmonella serovar Typhimurium
Cholera toxin (CTX)
Vibrio cholerae
Tcp pilus (CTX phage receptor)
V cholerae
Diphtheria toxin
Corynebacterium
diphtheriae
Shiga-like toxin
Enterohemorrhagic E coli
Botulinum toxin
Clostridium
botulinum
Erythrogenic toxin
Streptococcus
pyogenes
Location
Virulence
Factor
Organism
REGULATION
OF
VIRULENCE
ADHERENCE
&
COLONIZATION
P.23
before late colonizers such as Porphyromonas
and treponemes can attach.
gingivalis
TOXIN S
Host cell intoxication is one of the oldest-known mechanisms
associated with microbial virulence. Toxins block host cellular
defenses, elicit or create microbial nutrients, break down
anatomic barriers, and facilitate microbial transmission. In some
extreme cases, virulence can be entirely ascribed to the action of
a secreted toxin; examples include diphtheria and tetanus. In
these cases, antitoxin immunity is sufficient for protection
against disease. But most infectious diseases and pathogenic
strategies are not that simple. Microbial toxins exist in many
forms and with many different activities. Some are intrinsic to
the microbial cell wall, such as the lipopolysaccharide (or
endotoxin) of gram-negative bacteria, while other toxins are
secreted (exotoxins), either nonspecifically from the cell or
through specialized secretion systems, such as the type III and
type IV systems, directly into a host cell. Exotoxins of the first
type usually facilitate their own entry into a host cell by means
of a binding subunit that may take advantage of host cell
internalization pathways. In a manner and for reasons similar to
those described for adhesins, toxin expression is often tightly
regulated.
Microbial toxins can be classified on the basis of shared
mechanisms of action. The nature of the host cell receptor or
molecular target, the mechanism of activation, or the
intracellular trafficking of a microbial toxin may determine its
specificity of effect. One of the most well-known families of
microbial exotoxins is the group of bacterial ADP-ribosylating
toxins, which includes diphtheria toxin, cholera toxin, pertussis
Salmonella serovar
pathogens. Second, the
from a variety of
may provide a ready
pneumophila
mexicana
Examples
MANIPULATION OR AVOIDANCE
THE HOST IMMUNE RESPONSE
OF
with
antigen
presentation
Mycobacterium
tuberculosis
Adenovirus E3
CMV US11, US6
Protect host cell from oxidative stress
Molluscum
Interfere
with
Poxvirus
cytokine
soluble
responses
IL-1R
with
immunoglobulin
or
complement
lymphocyte
Bordetella
homing
Example
(Pathogen,
Virulence
factor)2
inflammatory
They are
their cognate
produces a
REFERENCES
Cotter PA, Miller JF: In vivo and ex vivo regulation of bacterial
virulence gene expression. Curr Opin Microbiol 1998;1:17.
Finlay BB, Falkow S: Common themes in microbial
pathogenicity revisited. Microbiol Mol Biol Rev 1997;61(2):
136.
Groisman EA, Ochman H: Pathogenicity islands: bacterial
evolution in quantum leaps. Cell 1996;87:791.
Guiney DG: Regulation of bacterial virulence gene expression
by the host environment. J Clin Invest 1997;99:565.
Hueck CJ: Type III protein secretion systems in bacterial
pathogens of animals and plants. Microbiol Mol Biol Rev
1998;62:379.
Hultgren SJ, et al: Pilus and nonpilus bacterial adhesins:
assembly and function in cell recognition. Cell 1993;73(5):
887.
Marrack P, Kappler J: Subversion of the immune system by
pathogens. Cell 1994;76:323.
Miao EA, Miller SI: Bacteriophages in the evolution of
2001
McGraw-Hill
Principles
of
Antimicrobial
Therapy
4
General Principles of
Antimicrobial
Therapy
Walter R. Wilson MD
Anti-infective agents such as inorganic salts, myrrh, and acidic
solutions have been used topically for centuries. For several
hundred years, European and Arabic physicians noted that the
administration of heavy metals such as arsenic, mercury, or
bismuth was effective against syphilis and other infections. The
modern era of antimicrobial chemotherapy began in the 1930s
with the introduction of sulfonamides and gathered momentum
in the 1940s with the discovery of penicillin and streptomycin.
Currently, antimicrobial agents are among the most widely used
classes of drugs. Worldwide expenditures for antimicrobial
agents exceed $20 billion annually, and antimicrobial agents
represent 2040% of drugs administered to hospitalized
patients. Although the choice of a single agent or a combination
of agents should be individualized for each patient, certain
general principles of therapy should guide the selection of
specific drugs. The following factors are important in
determining appropriate antimicrobial therapy for patients with
bacterial or fungal infections. The drugs of choice for the
treatment of infections are discussed in the chapters on specific
ETIOLOGIC
TESTING
AGENT
&
SUSCEPTIBILITY
concentration
Metronidazole
Rifampin
Chloramphenicol
Sulfonamides
Trimethoprim
Therapeutic concentration
Penicillin
Ampicillin1
Ticarcillin1
Piperacillin1
Mezlocillin
Nafcillin
Oxacillin
Ceftriaxone
Ceftizoxime
with
with
or
without
inflammation
inflammation
Cefotaxime
Ceftazidime
Cefepime
Cefuroxime
Aztreonam
Imipenem
Meropenem
Fluoroquinolones2
Vancomycin
Flucytosine
Fluconazole
Nontherapeutic concentration
with
or
without
inflammation
Aminoglycosides
Cefoperazone
Clindamycin
First-generation
Second-generation
Ketoconazole
Itraconazole4
cephalosporins
cephalosporins3
Amphotericin
preparations4
Macrolides
1 Penetration of beta-lactamase inhibitors, sulbactam,
clavulanate, and tazobactam may not achieve therapeutic
concentrations.
2 Fluoroquinolones that achieve therapeutic concentrations are
ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and
moxifloxacin.
3 Cefuroxime achieves therapeutic concentrations.
4 Achieves therapeutic concentration for treatment of
Cryptococcus
neoformans .
Table 4-1. Penetration of antimicrobial agents into the
cerebrospinal
fluid.
P.29
ADMINISTRATION
Once the decision is made to initiate antimicrobial therapy, the
next choice is between oral and parenteral administration, with
the later either intravenous or intramuscular. The oral
administration is appropriate for mild to moderately severe
infections in patients with a normally functioning
gastrointestinal tract. Some antimicrobial agents, such as
vancomycin, quinupristin-dalfopristin, and aminoglycosides, are
not absorbed after oral administration. They must be
administered parenterally. Others, like fluoroquinolones and
trimethoprim-sulfamethoxazole,
have
excellent
bioavailability
after oral administration and may be administered orally even in
patients with serious infections.
The mechanism of bacterial killing by antimicrobial agents
affects decisions regarding the amount of drug administered,
the frequency, and the route of administration (Table 4-2 ).
There are two major mechanisms of bactericidal activity by
antimicrobial agents (Table 4-3 ). The first is characterized by
saturation of the rate of killing by concentrations of antibiotic at
or near the minimum inhibitory concentration (MIC) of the
microorganism. Accordingly, increasing the concentration of
drug in serum does not result in an increased rate or magnitude
of bacterial killing. With these drugs, the duration of time of
drug concentration in serum or tissue that exceeds the MIC is
the major determinant of bacterial killing. This time-dependent
killing is observed with beta-lactams, vancomycin, macrolides,
and clindamycin. This phenomenon should be considered when
selecting optimal dosing of these antimicrobial agents. Failure to
do so may result in administration of unnecessarily high or
frequent dosages. With this mechanism of killing, the dosage of
an antimicrobial agent should be adjusted so that the
concentration in serum exceeds the MIC for 4050% of the
dosing interval. However, in bacterial meningitis, infective
endocarditis, or other infections in sites with diminished
antibiotic penetration, the administration of higher dosages of
antimicrobial agents, often at more frequent intervals, may be
two
P.30
UNDERLYING
HOST
FACTORS
or concomitant
prescribed.
medications
before
antimicrobial
Cephalosporins
Cefoperazone
Ceftriaxone
Macrolides
Erythromycin
Clarithromycin
Azithromycin
Teracyclines
Doxycycline
Minocycline
Fluoroquinolones
Trovafloxacin
Grepafloxacin
Others
Clindamycin
Metronidazole
Chloramphenicol
Rifampin
Table 4-4. Antimicrobial agents that do not require
dosage adjustments in patients with renal failure.
Age
Patient age, especially at the extremes of lifespan, is a major
factor that influences appropriate antimicrobial therapy. Elderly
patients may have a normal serum creatinine, but creatinine
clearance decreases with age. Antimicrobial agents that are
renally excreted may require reduction in dosages in elderly
patients, including those with a normal serum creatinine. Failure
to recognize this factor may result in accumulation of toxic
concentrations of antimicrobial agents in serum that may
produce serious consequences, including central nervous system
manifestations such as seizures or coma, nephrotoxicity,
hepatotoxicity, or ototoxicity. Similarly, renal function is
diminished in neonates. Dosages of antimicrobial agents that
are excreted by the kidneys should be altered.
Hepatic function is underdeveloped in neonates.
Chloramphenicol is metabolized in the liver. High serum
concentrations of unconjugated chloramphenicol may occur in
neonates, resulting in severe toxicity, such as shock and
cardiovascular collapse (gray-baby syndrome). Chloramphenicol
should not be administered to neonates. Sulfonamides compete
with bilirubin for binding sites on serum albumin and, when
administered to neonates, increase the concentrations of
unbound bilirubin in serum, which may result in kernicterus.
Consequently, sulfa drugs should not be administered to
neonates.
Tetracyclines readily pass the placental barrier and bind to bone
and teeth of neonates and children; therefore, the use of
tetracyclines should be avoided in this age group.
Fluoroquinolones cause arthropathy and cartilage damage in
puppies and have not yet been approved for use in children.
Fluoroquinolone use should be avoided, if possible, in children
who are <15 years of age.
Penicillins and cephalosporins
Hypersensitivity; gastrointestinal; diarrhea; disulfiram with
Methyltetrathiazole side chain (cefamandole, cefoperazone,
cefotetan)
Bone marrow suppression; nephrotoxicity;
hypoprothrombinemia with methyltetrathiazole
side
chain;
syndrome
Nephrotoxicity
Red man syndromehistamine mediated
C N1 -VII; neuromuscular blockade
C N1 -VIII; neuromuscular blockade
Clindamycin
Diarrhea
Hypersensitivity,
gastrointestinalnausea,
vomiting
Metronidazole
Gastrointestinalnausea, vomiting, metallic taste
Tetracyclines
Phototoxicity; impaired bone growth and teeth discoloration in
pediatric patients; skin, mucous membranes
Discoloration with prolonged minocycline use
Gastrointestinal; hypersensitivity; hepatitis; dizziness with
minocycline; lupus phenomena; pseudotumor cerebri
Rifampin
Orange secretions
Hypersensitivity; hepatic, bone
Quinupristin-dalfopristin
marrow
suppression
Muscle pain
Hypersensitivity;
hepatitis
Oxazolidinones; linezolid
Gastrointestinal,
headache
Bone marrow suppression; hypersensitivity
Chloramphenicol
Bone marrow suppression
Aplastic anemia; gray baby syndrome; neurotoxicity;
gastrointestinal;
hypersensitivity
Amphotericin compounds; amphotericin B; deoxycholate
Infusion-fever, nausea, vomiting, headache, hypotension,
hypertension, flushing, myalgias, nephrotoxicity
Hepatic; anemia; neurotoxicity
Lipid complex;
Hypokalemia,
hypomagnesemia
Infusion related; nephrotoxicity,
Cholesterol
sulfate
anemia
Itraconazole
Headache;
dizziness;
hypersensitivity
Gastrointestinal;
hepatotoxicity;
gynecomastia;
impotence;
More
Common
Less
Common
Agent(s)
Table 4-5. Toxicities of antimicrobial agents.
P.31
P.32
Other
Underlying
Conditions
TO
REFERENCES
Wilhelm MP (editor): Symposium on antimicrobial agents.
Mayo Clin Proc 1997;73:994.
Wilhelm MP (editor): Symposium on antimicrobial agents.
Mayo Clin Proc 1998;74:78.
Wilhelm MP (editor): Symposium on antimicrobial agents.
Mayo Clin Proc 1999;75:86.
Wilhelm MP (editor): Symposium on antimicrobial agents.
Mayo Clin Proc 2000;76: In press.
2001
McGraw-Hill
Prevention
in
Healthcare
Settings
5
Infection
Settings
Prevention
in
Healthcare
and
spread
of
antimicrobial-agent-resistant
infections;
healthcare
workers
through
immunization
programs,
practitioner per 250 occupied hospital beds led to lower infection rates
than programs with a lower ratio of expert infection control staff to
patients. Most infection control practitioners are nurses, although in
some settings physicians, epidemiologists, microbiologists, medical
technologists, or specific administrators may coordinate the infection
control program. Ideally, the infection control practitioner has
experience and knowledge in adult education techniques, epidemiology,
patient isolation strategies, and basic patient care. In addition,
knowledge of antimicrobial agents, infectious diseases, microbiology,
and basic principles of asepsis, sterilization, and disinfection is
essential. The infection control practitioner often consults with other
staff members on these issues and regularly assesses patient outcomes
to evaluate
Additionally,
observation
jeopardizing
THE
INFECTION
CONTROL
COMMITTEE
INFECTION CONTROL
PROCEDURES
POLICIES
&
performance
mea
P.35
sures to provide information to healthcare purchasers and consumers
on comparative performance of managed-healthcare plans. Finally,
several state and federal agencies promulgate regulatory directives
that have direct implications for infection control programs. Generally,
the infection control team ensures that staffers understand and comply
with such requirements.
INFECTION
MONITORING
&
PREVENTION
PATIENT
ISOLATION
blood;
all body substances, secretions, and excretions except sweat,
regardless of whether they exhibit visible blood;
nonintact
mucous
skin;
membranes.
precautions,
for
organisms
transmitted
by
PREVENTING
RESISTANT
ANTIMICROBIAL-AGENTINFECTIONS
affect the outcome of care for many patients and add to the expense of
treatment.
Antimicrobial-agent-resistant pathogens emerge and spread through
several convergent mechanisms. First, pathogens develop or acquire
the genetic traits responsible for resistance. Then they are introduced
into healthcare settings via patients, visitors, or healthcare personnel
or via contaminated materials. Antimicrobial therapy selects for strains
that express the resistance mechanism, which in turn increases their
capacity to spread to other patients or personnel.
Previous studies have demonstrated a relationship between the
emergence of resistant organisms and inappropriate or extended use of
antimicrobial agents, noncompliance with hand hygiene and other
infection control precautions, and indiscriminate use in food animals of
products containing antimicrobial agents.
Clinicians can act to prevent the emergence and spread of multidrugresistant infections in all healthcare settings. Professional societies,
healthcare organizations, healthcare purchasers, and federal agencies
have mounted efforts to promote judicious antimicrobial use. CDC has
developed a series of 12-step programs to prevent infections in various
patient settings. These programs emphasize four key strategies:
infection prevention (eg, through immunization and decreased use of
invasive devices in other procedures); effective pathogen-directed
antimicrobial treatment to eradicate infection when present; judicious
antimicrobial use; and prevention of person-to-person spread (eg,
through effective hand hygiene and patient isolation practices) (Table
5-2 ). Effective strategies for improving antimicrobial-agent
prescription practices are outlined in Table 5-3 . Of these, providing
individual clinicians or groups with feedback on prescription practices
and real-time decision support via computerized pharmaceuticalordering systems holds the most promise for effecting meaningful
improvements.
HAND
HYGIENE
Element
Standard
Precautions
Airborne
Precautions
Droplet
Precautions
Contact
Precautions
Prevent
infection
1 . Vaccinate.
Get influenza vaccine.
Give influenza/S pneumoniae vaccine to at-risk patients before
discharge.
2 . Get the catheters out.
Use catheters/invasive devices only when essential.
Use proper insertion/catheter care protocols.
Remove catheters/invasive devices when no longer essential.
Diagnose and treat infection
3 . Target the pathogen.
Diagnose infection.
Diagnose the pathogen.
Diagnose
antimicrobial
susceptibility.
4 . Access the experts.
Optimize regimen, dose, route, and duration.
Monitor response.
Adjust treatment when needed.
Use
antimicrobials
wisely
9.
8.
Don't routinely culture catheter tips.
Don't routinely culture through lines.
9 . Don't treat colonization.
Treat
Treat
Treat
Treat
transmission.
control
precautions.
methicillin-resistant Staphylococcus
Prescriber
education
Formulary
restrictions
Prior approval to start/continue
Standardized antimicrobial order forms
Drug utilization evaluation
ASEPSIS
Asepsis refers to the absence of microorganisms that are capable of
causing disease. Healthcare workers routinely use the following
methods to provide healthcare aseptically:
cutaneous antisepsisskin antisepsis designed to inactivate as
much of the skin flora as possible;
cleaningthe removal of soil and organic matter through a
physical or mechanical action involving the use of water and a
cleaning agent;
decontaminationa nonspecific term for removal of pathogenic
microorganisms from objects or equipment;
P.39
OCCUPATIONAL
HEALTH
ISSUES
INFECTIOUS
CONDITIONS
BLOOD-BORNE
OF
CONCERN
PATHOGENS
HCV-contaminated-needle
injuries
result
in
infection.
transmission
of
blood-borne
pathogens;
TUBERCULOSIS
Tuberculosis infection can be acquired and transmitted in healthcare
settings. Patients, healthcare personnel, and even visitors have been
sources of spread to others. Outbreaks of drug-resistant infection in
New York City in the early 1990s, with high attack rates observed
among exposed healthcare and prison personnel, illustrate the
tremendous morbidity this infection can still cause. Employee health
programs in settings where exposure to tuberculosis can reasonably be
expected are now charged with the responsibility for conducting
surveillance (skin testing) and postexposure follow-up. Current CDC
guidelines for preventing tuberculosis transmission in healthcare
facilities can be found at
http://www.cdc.gov/ncidod/hip/Guide/tb_excerpt.htm .
Tuberculosis prevention in healthcare settings relies first and foremost
on prompt recognition and isolation of suspected cases. Precautions
against airborne infectious agents include appropriate air containment,
filtration, and exchange to prevent tuberculosis transmission.
Appropriate respiratory protection may provide an additional measure
of safety, but it cannot substitute for proper ventilation. Patients
suspected of having tuberculosis should be placed in a room that meets
the precautionary specifications for such airborne pathogens, including
monitored negative air pressure in relation to the surrounding area,
612 air changes per hour, and appropriate discharge of air outdoors
or monitored high-efficiency filtration of room air before the air is
circulated to other areas in the hospital.
If these steps are not feasible in the short run, then patients should at
least be advised to don a surgical mask to reduce dissemination of
droplets that may desiccate to form infectious aerosols. Healthcare
personnel
suspected
respirator
respirator
VACCINE-PREVENTABLE
DISEASES
REFERENCES
Arias KM: Infection Control Tool Kit Series: Assessing and
Developing an Infection Control Program in the Acute Care Setting.
Association for Professionals in Infection Control and Epidemiology
Inc., 2000.
Beltrami EM et al: Risk and management of blood-borne infections
in health care workers. Clin Microbiol Rev 2000;13:385.
Epidemiol
1985;121:182.
1991;338:339.
Emerging
publication
(NIOSH)87-108. U.S.
2001
McGraw-Hill
Diagnosis
6
Laboratory
Diagnosis
Stenotrophomonas
maltophilia , or Burkholderia
cepacia; or grampositive bacteria, especially methicillin-resistant staphylococci
(methicillin-resistant Staphylococcus
aureus and methicillin-resistant
coagulase-negative
staphylococci)
and
vancomycin-resistant
Enterococcus spp. (VRE) and yeasts. Any of these nosocomial
pathogens may colonize the upper respiratory tract and spread to the
lower respiratory tract, secondary to endotracheal intubation. VRE
may also colonize the lower gastrointestinal tract and be spread from
one patient to another by fecal contamination. Mucositis, as the
result of total body irradiation and/or chemotherapy, may be
associated with septicemia caused by oral flora, especially
Streptococcus spp. of the viridans group and Candida spp.
Intravascular catheters may become infected with cutaneous flora or
nosocomial pathogens. These organisms include Staphylococcus spp.,
Streptococcus spp., and Corynebacterium spp., including
Corynebacterium
jeikeium , the same nosocomial gram-positive and
gram-negative bacteria described previously, and yeasts. All of these
organisms may be introduced into the bloodstream directly if
intravenous fluids or medications are injected through an infected
catheter port. Alternatively, these organisms may first colonize a
proximal port and over time ascend to the catheter tip.
Neutropenia secondary to chemotherapeutic agents is frequently
associated with bacteremia. Enteric gram-negative bacteria, notably
members of the family Enterobacteriaceae,
Pseudomonas spp., and
the gram-positive organisms Staphylococcus spp. or Enterococcus
spp., account for the majority of these bacteremias. Disseminated
fungal infections caused by Candida spp. or Aspergillus spp. may also
occur.
Because of the wide variety of microorganisms (bacteria, fungi,
viruses, and parasites) that can cause infections in
immunocompromised patients, in some instances, test-ordering
protocols may be useful to assure that appropriate specimen
processing and analyses are performed. This is especially important
for specimens that are obtained by using relatively invasive
procedures. For example, a standard battery of microbiology tests
should be considered for all specimens obtained by bronchoalveolar
Diagnosis
Parasitic
of Bacterial,
Infections
Fungal,
&
Blood
LA, CIE, COA, FA
Haemophilus influenzae, Neisseria meningitidis, Streptococcus
agalactiae (group B streptococcus ), Streptococcus
pneumoniae
LA
Cryptococcus
neoformans
RIA, EIA
Histoplasma
capsulatum
Acridine orange
Generally all bacteria but may be especially useful for detecting
organisms present at <104 colony forming units (CFU)/ml or
organisms that do not stain well with the Gram-stain method, eg,
Bartonella
henselae (agent of cat scratch disease, bacillary
angiomatosis, and peliosis hepatis)
Wright's, Giemsa, or Dark field examination
Borrelia
recurrentis (agent of relapsing fever) or other spirochetes
Giemsa or Diff-Quik (buffy coat)
Ehrlichia spp.
Dark field
Leptospira spp.
Acid-fast or auraminerhodamine
Mycobacteria spp. (occasionally positive when the quantity of
organisms is high as may occurwith severe immunodeficiency)
Wright'sor Giemsa (thick and and thin smears)
Plasmodium spp. (agents of malaria), Trypanosoma spp., Theileria
spp., Babesia microti)
H & E
Coccidioides
Microsporidia
H & E
FA
(especially
muscle,
kidney)
white
gondii
methenamine
silver,
calcofluor
FA
COA, LA, FA
Bordetella
pertussis
Streptococus
pyogenes (group A streptococcus)
Lower respiratory tract secretions including bronchial alveolar lavage
(BAL), transtracheal or transbronchoscopic aspirates and lung tissue
(transbronchoscopic biopsy or open-lung biopsy)
Gram
Generally all bacteria
Acid-fast or auraminerhodamine
Mycobacteria spp.
Modified acid-fast
methenamine
Giemsa
Toxoplasma gondii
Modified acid-fast
Cryptosporidium
parvum
Urethral exudate
Gram
EIA
EIA, FA
(male)
Neisseria
gonorrhoeae
Chlamydia
trachomatis
Cervical orvaginal exudate
Wet mount, Giemsa
EIA
EIA, FA
EIA, LA
Neisseria
gonorrhoeae
Chlamydia
trachomatis
Trichomonas
vaginalis
Trichomonas
vaginalis
Stomach4
Gram; Warthin-Starry or Giemsa(tissue)
silver,
calcofluor
Helicobacter
pylori 4
Small-bowel or colon tissue
Periodic acid Schiff
Tropheryma
whippelii (agent of Whipple's disease)
Acid-fast or auraminerhodamine
Mycobacterium spp.
H & E
A large varietyof protozoa or helminths [nematodes, cestodes
(tapeworms), or trematodes] may be identified.
Feces
Wet mount
Campylobacter
jejuni
Methylene blue
Evaluation for leukocytes associated with invasive bacterial diarrhea
EIA [O157 antigen and/or Shiga-like toxin (verocytotoxin)]
Escherichia coli O157:H7
EIA
Helicobacter
pylori
EIA, LA
Clostridium
difficile
EIA, FA
Giardia lamblia, Cryptosporidium
parvum,
Entamoeba
histolytica
Direct exam for ova and parasiteswet mount and fixed stains
(trichrome or iron-hematoxylin)
Permits identification of a large variety of protozoa and helminths
[nematodes, cestodes (tapeworms), or trematodes]
Anal swab
Pinworm
Genital chancre or chancroid lesion (male or female)
Gram
Donovan bodies (associated with Calymmatobacterium
granulomatis ,
agent of granuloma inguinale)
Dark-field
examination
Trepenoma pallidum (agent of syphilis)
Urine
Gram
Generally all bacteria (observation of 2 bacteria per oil
immersion field (1000) in a Gram-stained smear of a drop of
unconcentrated urine indicates ~ 105 bacteria/ml)
Acid-fast or auraminerhodamine
Mycobacteria spp.
EIA
Chlamydia
EIA, RIA
Legionella
Histoplasma
capsulatum
LA
Cryptococcus
neoformans
Dark-field
Leptospira spp.
Wet mount
Schistosoma
haematobium
1 LA, Latex agglutination; CIE, counterimmunoelectrophoresis; COA,
coagglutination; FA, fluorescent antibody; RIA, radioimmunoassay; H
&E, hematoxylin and eosin.
2 Rhodococcus spp. may not stain by the modified acid-fast method.
3 Coxiella
burnetti is a rickettsia-like bacterium.
4 Helicobacter
pylori can be detected by the rapid urease test on
tissue from a stomach biopsy or by the urea breath test.
Specimen
Stains
Immunologic
Tests1
Organism(s)
Detected
Blood
Broth based systems (manual or automated)
Effective broths that are most commonly used include tryptic or
trypticase soy broth with ~0.025% SPS; one bottle is vented
(aerobic), and the second is unvented (anaerobic); manual or
automated systems are incubated 57 d, or longer if fastidious
dermatitidis,
Cryptococcus
neoformans,
Coccidioides
immitis
Non-nutrient agar with overlay of bacteria (eg, E coli )
Acanthamoeba spp. (agents of chronic granulomatous amebic
encephalitis) and Naegleria spp. (agents of primary amebic
meningoencephalitis)
Bone marrow
BRA
Brucella spp.
BA, CBA, TGB(A)
Salmonella spp.
LJ, MB710, MB7H11, BACTEC 13A
Mycobacteria spp., Nocardia spp.
BCYE
Nocardia spp.
BHI, SD, IM
Fungi, especially Histoplasma
capsulatum
Brain tissue
BA, CBA, TGB
Most aerobic and facultative anaerobic bacteria
Abscess
Aerobic and facultatively anaerobic
Aerobic media: BA, CBA, TGB(A), and EMB or MAC
Anaerobic media: TGB(An)
Obligately anaerobic bacteria
BHI, SD, IM
Fungi
Non-nutrient agar with overlay of bacteria (eg, E coli )
Acanthamoeba spp.
McCoy cell culture
Chlamydia
trachomatis
Upper respiratory
BG or RIA
Bordetella
pertussis
BA
Streptococcus
pyogenes
BA and TA or CTA and LA
Corynebacterium
diphtheria
BHI, SD, IM
Fungi, especially Histoplasma
capsulatum from oral pharyngeal ulcers
Lower respiratory tract secretions (including BAL, transtracheal or
transbronchoscopic aspirates) and lung tissue (transbronchoscopic
biopsy or open-lung biopsy)
BA, CBA, EMB, or MAC, CNA; consider BC for cystic fibrosis patients
Most aerobic and facultatively anaerobic bacteria
BCYE
Legionella spp, Nocardia spp.
LJ, MB7H10, MB7H11, BACTEC 13A
Mycobacteria spp., Nocardia spp.
BHI, SD, IM
Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides
brasiliensis, Coccidioides immitis , Cryptococcus
neoformans,
Aspergillusi spp., and other fungi
Urethral exudate, cervical or vaginal exudate
CBA, TM
Neisseria
gonorrhoeae
McCoy cell culture
Chlamydia
trachomatis
SP4 glucose broth and agar
Mycoplasma hominis
Urine
BA and EMB or MAC
Most aerobic and facultatively anaerobic bacteria
FL, EH
Leptospira spp.
LJ, MB7H10, MB7H11, BACTEC 13A
Mycobacteria spp., Nocardia spp.
BYCE
Nocardia spp.
BHI, SD, IM
Fungi, especially Blastomyces
Gastric tissue
HA
Helicobacter
pylori
Small- or large-bowel tissue
dermatitidis
Media1
Bacteria
Bacteria
Brucella spp.2
TA, EIA
Francisella
tularensis
EIA
Helicobacter
pylori
EIA
Legionella spp.
IFA, EIA
Leptospira spp.
IHA
Bartonella
henselae (agent of cat scratch disease, bacillary
angiomatosis, and peliosis hepatis)
IFA, EIA
Borrelia
burgdorferi (agent of Lyme disease)
EIA, IB
Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci
CF, IFA, EIA
Mycoplasma
pneumoniae
CF, IFA, EIA
Aspergillus
niger,
Aspergillus
flavus
ID
Blastomyces
dermatitidis
CF
Candida albicans
ID
Coccidioides
CF, ID
Histoplasma
immitis
capsulatum
CF, ID
Sporothrix
schenckii
A
Parasites
Echinococcus
granulosa
EIA, IB
Entamoeba
histolyticum
EIA
Taenia solium (cysticercosis)
EIA
Toxoplasma gondii
EIA, FA
1 A, agglutination; CF, complement fixation; EIA, enzyme
Technique1
Blood
Both direct and culture-based techniques may be useful for
identifying common and uncommon bacterial, fungal, and parasitic
pathogens in blood. Some of the specialized testing methods shown
in Tables 6-1 and 6-2 are generally available only at reference
laboratories. If the clinician feels strongly that one of
P.52
these tests is useful, an aliquot of the specimen should be sent to a
reference laboratory. Direct test methods for the detection of
bacterial or fungal pathogens in blood are limited in the number of
different bacteria that they can detect and are less sensitive than
culture methods. Bacterial-antigen tests for commonly encountered
encapsulated organisms (Haemophilus
influenzae type b, Neisseria
meningitidis , or Streptococcus
pneumoniae ) are easy to perform
and available in most laboratories. A latex agglutination procedure
can be used to detect the yeast Cryptococcus
neoformans. .
Throat, nasopharyngeal, nasal secretions
Nasopharyngeal aspirates are superior to swabs for culturing
Bordetella
pertussis; swabs areadequate for the detection of S
pyogenes; nasal swabs are recommended for detecting carriers of
methicillin-resistant Staphylococcus
aureus .
Respiratory
secretions
Sputa may be induced with nebulized saline in patients who cannot
spontaneously produce sputa; spontaneously produced specimens
should be screened by microscopy for suitability for bacterial culture.
Eye
Secretions are obtained by swab from the palpebral conjunctiva;
NOTE: eye scrapings should be obtained by an ophthalmologist or
other trained person and plated directly at bedside if possible.
Blood
For adults, 2030 ml of blood are collected per phlebotomy (ie, one
set of blood cultures), and 10 ml are placed in each blood culture
receptacle; at least one 10 ml aliquotshould be cultured
anaerobically; three blood culture sets collected over a 24-hperiod
are adequate for diagnosing ~99% of bacteremias; peripheral blood
smears and malaria thick and thin smears should be performed at the
bedside.
Sterile body fluids other than blood and urine
Disinfect site if collection obtained percutaneously by aspiration;
sterile fluids (pleural, peritoneal, pericardial, and joint) are best
transported to the laboratory in ananaerobic transport system; some
studies have demonstrated the utility of blood culture media for
recovery of organisms from these sources.
Abscess
Tissue or fluid is superior to a swab specimen; swabs are especially
inadequate for anaerobic bacterial culture; use an anaerobic
area.
Specimen
Source
Considerations
with thick and thin blood smears. Thick smears permit screening for
malaria parasites, and speciation is possible by careful evaluation of
thin smears. When parasitemias are suspected, the laboratory
director should be notified so that proper processing and careful
evaluation of blood specimens are undertaken. In some cases,
referral of specimens to reference laboratories may be beneficial.
Other
Sterile
Body
Fluids
or
Tissues
Respiratory
Tract
Specimens
acid-fast
staining
method.
Feces
Enteric infections caused by Salmonella spp., Shigella spp., Yersinia
Intravascular
Catheters
Surveillance
Cultures
SEROLOGIC
TEST
METHODS
MOLECULAR
TEST
METHODS
Molecular test methods, including nucleic acid-probing and sequencing techniques, allow for the detection of pathogens directly
from human specimens. Molecular test methods and nucleic acid
amplification techniques, which are frequently available at most
reference laboratories are shown in Table 6-5 . These methods are
potentially useful for fastidious or slowly growing organisms like
Legionella spp., Bartonella spp., Mycobacterium spp., Borrelia
burgdorferi , and dimorphic fungi. The bacterial agent of Whipple's
disease, T whippelii , has never been recovered on culture and
Test
Method
Commercial
Kits
Diagnosis
of
Viral
Infections
CYTOLOGY
The simplest technique for viral diagnosis is cytologic examination of
specimens for the presence of characteristic viral inclusions, but this
approach is insensitive and applicable to only a few viruses,
especially herpes viruses. These intracellular structures may
represent aggregates of virus within an infected cell or may be
abnormal accumulations of cellular material resulting from the virusinduced metabolic disruption. Papanicolaou (Pap) smears may show
these inclusions in single cells or in large syncytia (aggregates of
cells containing more than one nucleus), as in a patient with herpes
simplex infection of the cervix. Cytology can be used to detect
infections with herpes simplex virus, varicella-zoster virus,
cytomegalovirus, human papillomavirus, and adenoviruses. Rabies
infection may also be detected by finding Negri bodies (rabies virus
inclusions) in brain tissue.
CULTURE-BASED
METHODS
tissue culture cells (eg, monkey kidney, human fetal lung, human
amnion, or human cancer cells) are inoculated with each viral
specimen.
Most clinically significant viruses can be recovered in at least one of
these cell cultures, but several clinically important viruses are not
isolated in these cells. For example, specimens submitted for the
identification of viruses such as human immunodeficiency virus,
coxsackie A virus, and rubella virus require, respectively,
cocultivation with normal human peripheral blood mononuclear cells,
inoculation of suckling mice, and the use of specialized cell cultures,
which are not generally available. Therefore infections caused by
these and several other viruses are most frequently diagnosed
serologically or by detection of virus-specific antigens or nucleic
acids.
Detection of the growth of a virus is by observation of changes in the
cell culture monolayer [cytopathic effect (CPE)]. Characteristic CPEs
include changes in cell morphology, cell lysis, vacuolation, syncytia
formation, and presence of inclusion bodies. Inclusion bodies are
histologic changes in cells caused by the presence of viral
components or changes in cell structures. With experience a
technologist can distinguish CPE characteristics of the major virus
groups. The observation of which cell culture exhibits CPEs and the
rapidity of viral growth can be used for the presumptive identification
of many clinically important viruses. This approach for identifying
viruses is similar to bacterial identification based on growth and
morphology of colonies on selective, differential media. Some viruses
do not readily cause CPEs in cell lines typically used in clinical
virology laboratories. However, some of these can be detected by
other techniques, such as (1) erythrocyte hemadsorption onto cells
infected with paramyxoviruses or mumps virus or (2) interference
with the replication of other viruses (eg, picornaviruses cannot
replicate in cells previously infected with rubella virus; this is known
as heterologous interference).
In contrast with the intrinsic delay of antibody studies, the results of
viral culture can be surprisingly rapid. Almost 50% of all viral
isolates can be reported within 3 to 4 days of culture, with herpes
Adenoviruses
6.4
Parainfluenzaviruses 1 and 3
6.4
overall
4.1
Virus
average
Timing
of
Specimen
Collection
nervous
Transport
system
to
manifestations.
Laboratory
Interpretation
of
Culture
Results
P.59
tract; adenoviruses in the oropharynx and intestinal tract). Herpes
simplex virus, cytomegalovirus, varicella zoster virus, and EpsteinBarr virus may remain latent for long periods and then become
reactivated in response to a variety of stressful stimuli, including
other infectious agents. In this setting their detection may not be
significant, may merely represent a secondary problem complicating
the primary infection (eg, herpes simplex virus cold sores in
patients with bacterial sepsis), or may be associated with significant
disease, especially in the immunocompromised patient.
Respiratory
syndrome
++++
Adenoviruses 2
Influenza virus2
Parainfluenza
virus2
Respiratory syncytial
Rhinoviruses
+++ nasal
virus2
Enteroviruses
Dermatologic and mucous membrane disease
+
++++
Vesicular
Enterovirus (hand, foot, mouth
++
+++
+++ (vesicle fluid or scraping)
Herpes
simplex2
Varicella-zoster2
++
Exanthematous
++
Enterovirus
+++
Measles3
Rubella3
syndrome)
Meningoencephalitis
++
+++
Arboviruses
Enteroviruses6
++++
Herpes simplex6
Lymphocytic
choriomeningitis 3
Mumps virus
Gastrointestinal
++
Adenoviruses4
Rotavirus5
Congenital and
++
+
perinatal
++
++
Cytomegalovirus
+++
Blood
Enteroviruses
Herpes simplex virus
Vesicle fluid, blood
Eye syndrome
++++
Adenoviruses
++
Conjunctival swab or scraping
Herpes simplex virus
Varicella-zoster
virus
Cytomegalovirus
infection
+
++++
blood
Myocarditis,
pericarditis
++
++++
+
Coxsackie
Pericardial fluid
1 Specimens indicated beside the disease categories should be
obtained in all instances; others should be obtained if the specific
virus is suspected.
2
Throat/Nasopharynx
Stool
CSF
Urine
Other
Source
Considerations1
Stool
Obtain as for bacteriologic culture; if a specimen cannot be passed, a
rectal swab of feces may be obtained.
Cerebrospinal fluid
Obtain 1 ml as for bacteriologic culture.
Urine
Obtain as for bacteriologic culture.
Skin or mucosal scraping
Obtain with swab in transport medium.
Biopsy material
Use sterile technique and submit in a sterile container (urine culture
container).
Blood for culture
Submit 3ml of heparinized blood.
Blood for serologic studies
Submit at least 5 ml of clotted whole blood (red-top vacutainer tube;
in certain viral syndromes (lower respiratory) an acute-phase
specimen should be submitted; if a virus is notisolated, a
convalescent specimen should be obtained 7 days after the
acute specimen;certain viral illnesses (rubella, rubeola, hepatitis,
arbovirus, and encephalitis) are diagnosed most readily by serologic
studies.
Transportation
Transport specimens as rapidly as possible, using a messenger
service; specimens should be stored and transported at refrigerator
temperature (4C); do not freeze.
Specimen
Procedures
DETECTION
OF
VIRAL
ANTIGENS
SEROLOGIC
TEST
METHODS
and
false-negative
results.
antiviral
antibody.
Interpretation
of
Serologic
Results
Serologic
Panels
Myocarditis/pericarditis
Group B coxsackievirus types 15, influenzaviruses A and B,
cytomegalovirus
Hepatitis
Hepatitis viruses
Exanthem
Rubella virus, measles virus, varicella-zoster virus
Central nervous system infections
Western and eastern equine encephalitis virus, California encephalitis
virus, St. Louis encephalitis virus, lymphocytic choriomeningitis virus,
measles virus, Epstein-Barr virus, rabies virus
Heterophile-negative
mononucleosis
syndromes
Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus
Respiratory
infections
Influenza viruses A and B; respiratory syncytial virus; parainfluenza
virus types 1, 2, and 3; adenoviruses
Clinical
Table
Syndrome
Panels
MOLECULAR
TEST
METHODS
amplification.
P.64
REFERENCES
Diagnosis
Parasitic
of Bacterial,
Infections
Fungal,
&
197;24:403.
avium-
JM: Specimen
Management
in
Clinical
Microbiology.
Committee
for
Clinical
Microbiology
Standards:
Diagnosis
of
Viral
Infections
2001
McGraw-Hill
> Table of Contents > Section II - Clinical Syndromes > 7 Infections of the Central Nervous System
7
Infections of the Central Nervous
System
Zell A. McGee MD*
*The author is grateful to J. Richard Baringer, MD, Professor of
Neurology, University of Utah School of Medicine, for his careful
review of this chapter, his constructive suggestions, and the several
sections he wrote on subjects that represent special areas of his
expertise.
The signs and symptoms of infections of the central nervous system
(CNS) are not specific to each type of infection (eg, brain abscess or
meningitis), but certain clusters of signs and symptoms can limit the
range of CNS infectious diseases that must be considered. The
following elements of a patient's history, signs, and symptoms may
indicate or accompany meningeal or parenchymal CNS infections,
especially if one or more occur in the same patient: fever; headache;
nausea and vomiting; confusion, obtundation, or uncharacteristic
behavior; stiff neck; or focal neurologic dysfunction.
When these signs and symptoms follow those of infection of the upper
or lower respiratory tract, the cluster suggests the transition of the
respiratory tract infection to bacteremia or viremia and then its
progression to meningitis or another type of CNS infection.
ACUTE
General
BACTERIAL
MENINGITIS
Considerations
1.
DISEASE
(DIAGNOSIS)
Diagnosis/Disease
Most Likely
Organism
Best
Antimicrobial1
diseases.
Personal
Risk
Factors
The bacterial pathogen most likely to cause meningitis varies with the
site of acquisition and the age of the patient (Table 7-2 ). Patients
who are asplenic or alcoholic or who have preexisting ear or paranasal
sinus infections are at greater risk of having infections with S
pneumoniae. .
Among patients who have conditions that allow access of stool to CSF,
for instance, a pilonidal sinus or Strongyloides
stercoralis infestation,
Age Group
Most
Likely
Organism(s)
Community
Risk
Factors
Physical
Examination
Laboratory/Imaging
Studies
aureus or Pseudomonas
aeruginosa should be
media
fulminans
Ecthyma
gangrenosum
S pneumoniae
Stool flora, probably E coli
Young adults, N meningitidis
Children, H influenzae
N meningitidis
P aeruginosa > candida > other fungi, other gram-negative bacilli
Physical
Sign
Bacterial
meningitis
Polys
<50% of blood
Gram
Culture
PCR for some
Tuberculous
meningitis
Lymphocytes 1
<50% of blood
Ziehl-Nielsen
Culture
PCR2
Fungal meningitis
Lymphocytes
Low
India ink3
Culture
Antigen 4
Antibody5
Viral meningitis
Lymphocytes 6
Normal7
CSF culture
PCR
Stool culture
Carcinomatous
meningitis
Lymphocytes, tumor cells
Very low
Cytologic exam
1 PMN cells may be present early in disease.
2 Limited availability of test.
3 For cryptococci; relatively insensitive.
4 For cryptococcus.
5 For coccidioides.
6 PMN cells may predominate in first 24 h.
7 May be low in mumps.
Type of
Meningitis
Leukocyte Cell
Type
Glucose
Stain
Other
Tests
Differential
Diagnosis
Cautions
Prior
to
Lumbar
Puncture
Treatment
To put the imperative for speed in initiating therapy into more
concrete terms, some experts have suggested a goal of allowing no
more than 30 min from the time of clinical diagnosis to starting an IV
infusion of the best antibiotic for the most likely organism to be
causing the meningitis. A suggested use of the 30 min appears in
Table 7-5 and assumes that the above-mentioned precautions and
procedures regarding signs of a mass lesion will be observed.
Intravenous antimicrobial agents are the optimal types of therapy for
acute bacterial meningitis. Specific, optimal antimicrobial agents for
the therapy of acute meningitis that is known or suspected to be
caused by particular organisms are reviewed in Table 7-6 . The
antimicrobial agent chosen should meet a number of criteria, which
are listed under Best Antimicrobial in Table 7-1 . As noted,
the antimicrobial agent chosen should avoid the patient's special
vulnerabilities. For example, if possible, the patient should not be
given an antibiotic to which he or she is allergic; patients with
myasthenia gravis, which causes intrinsic neuromuscular blockade,
should not be given aminoglycosides, which may induce further
neuromuscular blockade; and, if possible, patients with hemolytic
anemias such as sickle cell disease should not be given
chloramphenicol,
which
diminishes
erythrocyte
production.
Complications
It may be difficult to separate the complications of the bacteremia and
septicemia that are associated with the meningitis from the
complications of the meningitis per se. The complications of the
septicemia include coagulation disorders such as disseminated
intravascular coagulation (manifested in meningococcemia as a
petechial rash and purpura fulminans or in some cases as
hemorrhagic
adrenal
necrosisWaterhouse-Friderichsen
syndrome), myocarditis with congestive heart failure, shock, and
prolonged fever. The more frequent complications of the meningitis
per se result from the inflammatory reaction, including tumor necrosis
factor-alpha (TNF-) induction, which may cause damage to cranial
nerves with resulting ophthalmoplegias, deafness, and blindness.
Seizures or hydrocephalus may occur as early or late complications. In
meningitis caused by H influenzae in children, some of these
complications appear to occur less frequently if dexamethasone is
administered in conjunction with antimicrobial agents to diminish the
production of TNF- (see Table 7-6 ). No comparable information is
available for meningitis in adults or for meningitis caused by other
bacteria.
Prognosis
Although the mortality rate for bacterial meningitis varies with the
specific etiologic agent and the clinical circumstances, especially the
age of the host, with early diagnosis and prompt, targeted (not broadspectrum) antimicrobial therapy, the mortality rates for meningococcal
and H influenzae meningitis are generally < 10% and 5%,
respectively. Pneumococcal meningitis has a worse prognosis, with
mortality rates of ~20%; in addition, neurologic complications, such
as hydrocephalus, subdural empyema, seizures, and cranial nerve
palsies, occur more frequently in meningitis caused by S pneumoniae.
Prevention
&Control
influenzae meningitis in
P.71
P.72
states, less than half of the eligible children have been immunized.
N
meningitidis
Adults: Penicillin G, 3 4 million U by volutrol over 30 min every 4 h
Children older than 28 d: Penicillin G,3 50,000 U/kg IV every 6 h
Children 7 d or younger: Penicillin G,3 50,000 U/kg IV every 12 h
Penicillin-allergic
patients:
Chloramphenicol
Some experts add dexamethasone (as described below for Hib)
Penicillin may cure the meningitis but fail to eradicate the nasal
carrier state of the patient. To prevent postdischarge transmission
of meningococci from the patient to siblings or other contacts,
eradicate the carrier state of the patient with rifampin before
discharge.4 For children older than 1 m of age, give rifampin,
10 mg/kg (maximum dose, 600 mg) PO every 12 h for a
total of 4 doses in 2 d. For children 28 d old, the
dosage is 5 mg/kg PO every 12 h for a total of 4 doses in 2
d. For teenagers or adults, the dosage is 600 mg PO every
12 h for a total of 4 doses in 2 d.
Group B streptococci
Adults: ampicillin, 2.0 g IV every 4h + cefotaxime, 2.0 g IV every
6 h
Neonates: ampicillin, 50 mg/kg IV every 12 h + cefotaxime, 50
mg/kg IV every 12 h
With either regimen, repeat CSF exam/culture 2436 h after
start of therapy.
S
pneumoniae
(pneumococcus)
meropenem.
7 Others prefer to treat adults
with sulfamethoxazole-trimethoprim,
1520 mg/kg, trimethoprime quivalent, in equally divided doses
given every 68 h. Sulfamethoxazole-trimethoprim is
contraindicated in infants <2 mo of age.
8 Some clinical microbiology laboratories save the first isolate from an
infected site, and when the same microorganism is subsequently
isolated from that site, report the first set of susceptibility data. This
pratice may result in failure to detect the transition of an initially
cephalosporin-susceptible isolate to a cephalosporin-resistant isolate
during cephalosporin therapy. Thus, susceptibility testing should be
done on each successive isolate in meningitis caused by Pseudomonas,
Enterobacter , or Acinetobacter spp., if the patient is treated with a
cephalosporin.
Organism
Regimen 1 , 2
organisms.
influenzae
Meningitis.
ASEPTIC
Essentials
MENINGITIS
of
SYNDROME
Diagnosis
meningitis
Brain abscess
Contiguous sinusitis,
Epidural abscess
Fungal meningitis
HIV meningitis
otitis
General
Considerations
Clinical
Findings
meningeal
inflammation.
Medical
P.75
Differential
Diagnosis
Viral
meningitis
(most)
Antibiotics
Trimethoprim-sulfamethoxazole1
Joffeet al, 1989
Ciprofloxacin
Asperilla & Smego, 1989
Immuno-suppressives
OKT-3 monoclonal antibody2
CDC, 1986; Martin et al, 1988
Anticonvulsants
Carbamazepine
Simon et al, 1990
Nonsteroidal anti-inflammatory
Ibuprofen Naproxen
Jensenet al, 1987
drugs
Drug
Reference
Complications
The complications of aseptic meningitis syndrome depend on its
etiology. If caused by a pharmaceutical product such as ibuprofen,
Treatment
As with bacterial meningitis, the antimicrobial therapy should be
specifically targeted toward the most likely organism to cause the
aseptic meningitis syndrome. For instance, the most likely organism to
cause an epidural abscess is S aureus , whereas multiple brain
abscesses associated with endocarditis are likely to be caused by the
same organism that is infecting the heart valves.
P.76
In some patients, the best therapy for aseptic meningitis syndrome
may be stopping a drug that is causing the meningitis. For instance, in
a patient with AIDS who develops aseptic meningitis syndrome while
receiving sulfa-trimethoprim prophylaxis against Pneumocystis
carinii
infections, it would be reasonable, after excluding infectious causes of
the aseptic meningitis syndrome, to change the prophylaxis from
sulfa-trimethoprim, which can cause an aseptic meningitis syndrome
(see Table 7-9 ), to pentamidine for Pneumocystis prophylaxis.
Antiviral therapy is not indicated for most cases of viral meningitis.
Prognosis
The prognosis of aseptic meningitis syndrome is the same as that of
its underlying cause. For instance, neoplastic meningitis as the cause
of aseptic meningitis syndrome has a dire prognosis, whereas druginduced aseptic meningitis syndrome and virus-caused aseptic
meningitis syndrome have an excellent prognosis.
Prevention
&
Control
of
Diagnosis
Frontal
Lobe
Infections
Creutzfeldt-Jakob
Disease
P.77
INFECTIONS PRESENTING
SYNDROMES
Essentials
of
AS
STROKE
Diagnosis
splenic
(abdominal
pain).
Bacterial
Endocarditis
Fungal
Infections
Other
Meningeal
Infections
INFECTIONS PRESENTING
CORD
SYNDROMES
Essentials
of
AS
SPINAL
Diagnosis
Epidural
Abscess
Genital
Herpes
of
Diagnosis
these
and
these
consider
Bacterial
Endocarditis
Herpes
Simplex
Encephalitis
Virus-Induced
Arbovirus-Induced
Encephalitis
Brain
Abscesses
Subdural
Empyemas
Cerebral
Venous
Sinus
Infections
Fungal
Infections
Fungi may cause focal disease in the brain with a constellation of signs
and symptoms similar to those considered above. Fungal infections are
most often encountered in hosts with compromised cell-mediated and
other types of immunity. They are thus seen more often in patients
with AIDS, lymphoma, Hodgkin's disease, leukemia, or advanced
diabetes or in patients receiving cytotoxic or immunosuppressive
regimens. Cryptococcal infection usually presents as severe meningitis
and should be considered in the differential of acute bacterial
meningitides discussed earlier. Infection caused by Mucor or Rhizopus
species occurs most frequently in diabetics with multiple episodes of
acidosis. The infection may spread from the oropharynx or paranasal
sinuses into the skull base, involving the orbit, cranial nerves two
through six, and the cavernous sinus as well as the carotid artery. The
clinical picture of a red or proptotic eye with third or sixth nerve
paralysis in a diabetic should prompt aggressive biopsy and culture of
affected tissues as well as culturing of the nasopharynx and sinuses
for Mucor or Rhizopus species. Optimal management requires a
combination of surgical debridement and therapy with high-dose
amphotericin B or lipid-formulated amphotericin B.
Toxoplasmosis
Toxoplasmosis in the CNS presents most commonly with multifocal
lesions, causing focal deficits, seizures, and impairment of cognitive
functions over a period of days to weeks. Before the advent of AIDS,
CNS toxoplasmosis was encountered only rarely, and then usually in
the setting of Hodgkin's disease, lymphoma, or other states of severe
immunosuppression. It has become a frequent complication in AIDS
patients and should be immediately considered in the AIDS patient
who develops multifocal neurologic deficits over a period of a few days
to weeks.
The disease is often easily visualized by contrast-enhanced CT or
(preferably) MRI scans, most often appearing as multicentric solid or
ringlike enhancing lesions in the brain; the appearances are often
quite characteristic but can be mimicked by cerebral lymphoma, also
INFECTIOUS
DISORDERS
CRANIAL NERVES
Essentials
History:
of
antecedent
INVOLVING
Diagnosis
meningeal
infection;
infections
of
paranasal
Botulism
&
Pseudobotulism
P.83
contains the anticholinergics atropine and scopolamine, which are
highly concentrated in the seeds and can cause serious illness or
death. Teenagers seeking mind-altering experiences sometimes
experiment with Datura , only to die, probably from the cardiotoxic
principle in the plant. They usually present with the pseudobotulism
syndrome (fixed, dilated pupils and dry mouth), which is
distinguishable from true botulism primarily by the history of contact
with the Datura plant or its seeds and by the hallucinations, which are
not a feature of true botulism. If the cardiovascular system is stable,
the patients usually improve over time without therapy, other than
emptying the stomach, using activated charcoal, or both; however, if
the patients manifest profound toxicity, including bradycardia or
tachycardia, the use of the antidote physostigmine should be
considered.
Rabi es
Rabies should also be considered in the differential diagnosis of
patients presenting with dysphagia and dysarthria, with or without
hydrophobia and laryngeal spasms. Rabies must be considered in any
patient who has traveled to third-world countries and who has had any
contact with potentially infected animals. Skunks, raccoons, and bats
are the main animal reservoirs of rabies in the United States.
Treatment with human immune globulin and diploid cell-derived
vaccine is very effective for individuals exposed to or bitten by rabid
animals, but it is ineffective once neurological symptoms have
developed. It is important for persons in close contact with the
victims, whose body fluids may be infectious or for others who have
had contact with the same or other infected animals to receive
postexposure prophylaxis. A detailed review of the indications and
procedures for postexposure prophylaxis has been provided by the
Centers for Disease Control and Prevention (CDC/MMWR, 1999 ).
REFERENCES
Asperilla MO, Smego RA Jr: Eosinophilic meningitis associated with
ciprofloxacin. Am J Med 1989;87:589.
Attia J et al: Does this adult patient have acute meningitis? JAMA
1999;282:175.
Ballas ZK, Donta ST: Sulindac-induced aseptic meningitis. Arch
Intern Med 1982;142:165.
Baker ND et al: The efficacy of routine head computed tomography
(CT scan) prior to lumbar puncture in the emergency department. J
Emerg Med 1994;12:597.
of
1990;40:1820.
Jensen S et al: Ibuprofen-induced meningitis in a male with
systemic lupus erythematosus. Acta Med Scand 1987; 221:509.
P.84
Joffe
AM:
Trimethoprim-sulfamethoxazole-associated
aseptic
meningitis: case reports and review of the literature. Am J Med
1989;87:332.
Koskiniemi M et al: Herpes encephalitis is a disease of middle aged
and elderly people: polymerase chain reaction for detection of
herpes simplex virus in the CSF of 516 patients with encephalitis. J
Neurol
Neurosurg
Psychiat
1996;60:174.
during
intravenous
ciprofloxicin
1996;347:921.
2001
McGraw-Hill
> Table of Contents > Section II - Clinical Syndromes > 8 Infections of the Eye & Orbit
8
Infections of the Eye & Orbit
Marlene L. Durand MD
EYELID
Essentials
INFECTIONS
of
Diagnosis
General
Considerations
The eyelids contain meibomian glands (Figure 8-1 ) that secrete sebum, an
lubricate and protect the corneal surface. Inflammation of these glands may
swelling in the lid (hordeolum and chalazion) or redness and irritation of the
(blepharitis).
HORDEOLUM
CHALAZION
BLEPHARITIS
often associated rosacea or seborrheic dermatitis. The lid margins are red a
skin scales clinging to the eyelashes. Symptoms are burning and itching of t
includes daily gentle lid scrubs with a baby shampoo to remove scales and
bacitracin ointment at night. Tetracycline therapy may help if there is assoc
Key
Terms
PRESEPTAL
CELLULITIS
used in children as initial therapy, because some children with preseptal cell
bacteremic.
Figure 8-1. The meibomian glands of the eyelids. (Adapted from Last RJ: Eu
of the Eye and Orbit. W.B. Saunders, 1976.)
P.86
The tear film lubricates and nourishes the corneal surface and helps to focus
three layers. The outer lipid layer, produced by the meibomian glands, helps
the middle aqueous layer. Chronic meibomitis, as occurs in chronic blepharit
lipid layer, allowing excessive evaporation of the aqueous layer, corneal dry
corneal defects. The middle aqueous layer is the largest layer and is produce
The inner layer is composed of mucin produced by goblet cells in the conjun
these goblet cells, as occurs in Stevens-Johnson syndrome, leads to severe
damage.
Lid
Infections
Hordeolum
Blepharitis
Preseptal
cellulitis
Staphylococcus
aureus
S aureus
S aureus , group A streptococci, Streptococcus
Topical
bacitracin
or
pneumoniae,
Haemophilus
erythromycin
Same
Cefuroxime (orally or IV) (clarithromycin or clindamycin + ciprofloxacin)
Lacrimal
System
Infections
Dacryocystitis
Dacryoadenitis(acute)
Canaliculitis
S aureus, S pneumoniae, H influenzae
Same
Actinomyces
israelii
Ampicillin-sulbactam
Same
Irrigate
Orbital
with
or
cefuroxime
IV
penicillin
Infections
influenzae , anaerobes
Suggestions for empiric therapy in patients who are highly penicillin allergic
parentheses. Note that ciprofloxacin is not approved for use in children. Trea
these conditions requires prompt surgical drainage (see text).
Condition
Common
Organisms
Empiric
Therapy1
LACRIMAL
Essentials
Epiphora
SYSTEM
of
(excessive
INFECTIONS
Diagnosis
tearing).
Dacryocystitis: swelling and redness below the medial canthus (nasal side
Canaliculitis:
pouting
puncta.
Dacryoadenitis: swelling and redness in the orbit above and lateral to the
General
Considerations
The lacrimal system produces and drains the aqueous middle layer of the tea
produced
P.87
by the lacrimal gland, located in the upper outer portion of the globe. They
surface of the eye and drain via canaliculi into the lacrimal sac and the nose
Figure 8-2. Schematic diagram of a sagittal section of the eyelids and anter
or septum is the connective tissue skeleton of the lids.
DACRYOCYSTITIS
CANALICULITIS
Figure 8-3. The lacrimal system. (Adapted from Barza M & Baum J: Ocular
Am 1983;67: 131.)
DACRYOADENITIS
ORBITAL
INFECTIONS
Essentials
of
Diagnosis
with
extraocular
movements.
P.88
Limitation of extraocular movements (except with early orbital cellulitis)
Fever
and
leukocytosis.
General
Considerations
The bony orbit (eye socket) is shaped like a cone placed horizontally in the
medial wall is formed by the paper-thin lateral wall of the ethmoidal sinus,
Figure 8-4. Schematic diagram of the five main categories of orbital infecti
cellulitis; B, orbital cellulitis; C, subperiosteal abscess; D, orbital abscess; E
thrombosis. (Adapted from Chandler JR, Langenbrunner DJ, Stevens FR: The
complications in acute sinusitis. Laryngoscope 1970;80:1414.)
P.89
ORBITAL
CELLULITIS
and usuall
The patien
adults. Fev
be swollen
(edema) and injection of the conjunctiva. There is proptosis, but this may no
measured by an ophthalmologist. Visual acuity may be decreased, and there
movement. With progression of the infection, there is limitation of extraocul
characteristic findings on computed tomography (CT) are proptosis and stran
Evidence of sinusitis on the same side is often seen. Pathogens include S au
ORBITAL
ABSCESS
An orbital abscess is a collection of pus within the orbit. This is most often f
superior part of the orbit because infection usually begins in the ethmoid or
marked limitation of eye movement, and the eye usually looks down and
the site of the abscess). Other signs and symptoms are similar to those of o
scan, a low-density collection within the orbit is seen. Treatment requires im
abscess and IV antibiotics directed against S aureus , streptococci, anaerobe
nafcillin plus ceftriaxone or ampicillin-sulbactam).
SUBPERIOSTEAL
ABSCESS
A subperiosteal abscess is a collection of pus between the bony wall and per
Because this is usually an extension of infection from the ethmoidal sinuses,
often involved. It is difficult to distinguish a subperiosteal abscess from an o
clinical grounds; both produce fever, leukocytosis, lid swelling, redness, wa
chemosis, decreased vision, and marked limitation of extraocular movement.
abscess, the eye is usually nearly fixed in position looking down and out.
subperiosteal collection is seen. The bacteriology and treatment are the sam
immediate surgical drainage plus IV antibiotics (eg, nafcillin plus ceftriaxone
CAVERNOUS
SINUS
THROMBOSIS
CONJUNCTIVITIS
Essentials
Diffuse
of
erythema
Diagnosis
(conjunctival
injection).
General
Considerations
(see Figure 8-2 ). It does not cover the cornea, but abuts the corneal epithe
(corneal-scleral
border).
HYPERACUTE
CONJUNCTIVITIS
ACUTE
CONJUNCTIVITIS
P.91
(larger than papillae) give the inner surface of the lids a pebbly appearance
adenopathy is typical of viral conjunctivitis.
I. Hyperacute
Copious, purulent
+
+/+
Neisseria
gonorrhoeae
Rarely, N meningitidis
II. Acuteviral EKC1
Watery
+
+
+
Adenovirus
Highly contagious
Pharyngoconjunctival
Watery
+
-
fever
+
Adenovirus 3
Pharyngitis common
III. Acutebacterial
Purulent
+
Staphylococcus aureus, Streptococcus
Haemophilus
aegyptius (tropics)
pneumoniae,
Haemophilus
influenzae
IV. Chronic
A. Bacterial
Minimal, purulent
+
-/+
S aureus, Moraxella lacunata
Associated with chronic blepharitis
B. Chlamydial
1. Inclusion conjunctivitis
Minimal
+ (lower lid)
+
Serotypes DK
Sexually
transmitted
2. Trachoma
Minimal
+ (upper lid)
+
+
Serotypes AC
Fomite transmitted; Africa, Middle East, India
1 EKC, Epidemic keratoconjunctivitis.
Type
Discharge
Follicles
Papillae
Preauricular
Adenopathy
Corneal
Involvement
1.
ACUTE
VIRAL
CONJUNCTIVITIS
reported.
patients should stay home from work or school for 2 wk. Symptoms may per
2.
ACUTE
BACTERIAL
CONJUNCTIVITIS
Culture of the exudate is usually not required, but should be done in any pat
respond to therapy. Symptoms are self-limited and will last 710 d if untre
treated. Topical preparations are listed in Table 8-2 ; bacitracin, erythromyc
bacitracin/polymyxin ointments are reasonable choices for empiric therapy.
CHRONIC
CONJUNCTIVITIS
Ciloxan
0.3%
Ofloxacin
(s)
Ocuflox
0.3%
Erythromycin
(o)
0.5%
Gentamicin (o, s)
Genoptic
0.3%
Tobramycin (o, s)
Tobrex
0.3%
Sulfacetamide
Cetamide
(o)
10.0%
Sulfacetamide (s)
Ocu-Sul-10,15, 30
10%, 15%,30%
Sulfisoxazole (s)
Gantrisin
4.0%
Tetracycline (o, s)
Achromycin
1.0%
Combinations
Bacitracin, polymyxin (o)
Polysporin
The trade name list is not all-inclusive. Many of these antibiotics are also
preparations.
Antibiotic 1
Trade Name2
Concentration
1.
TRACHOMA
2.
INCLUSION
CONJUNCTIVITIS
KERATITIS
Essentials
(CORNEAL
of
Diagnosis
vision.
Photophobia.
No fever or leukocytosis.
ULCER)
General
Considerations
The cornea is only 0.51.0 mm thick, but it and the overlying tear film acc
refractive power of the eye. It has no blood vessels, but has many nerve fib
abrasions are painful). Its barrier to infection is a 5-cell-layer-thick epitheliu
with the conjunctiva. Microbes may infect this epithelium (epithelial keratitis)
interstitium (interstitial keratitis), or both (ulcerative keratitis).
BACTERIAL
KERATITIS
In the United States, ~30,000 cases of bacterial corneal ulcers are treated
usually cause a craterlike ulcer when they infect the cornea (ulcerative kera
complains of a red, painful eye; the redness is more intense near the limbus
show the defect in the cornea and a focal opacity. There may be a sterile hy
leukocytes in the anterior chamber) (see Figure 8-5 ).
Figure 8-5. Typical bacterial corneal ulcer with sterile hypopyon. The patient
to conjunctival injection. The corneal ulcer appears white.
A major risk factor for ulcerative keratitis is contact lens wear. Most bacteri
cannot penetrate an intact corneal epithelium. Contact lenses can cause brea
Soft contact lenses worn overnight carry an especially high risk of keratitis:
with daily-wear lenses. Other risk factors for keratitis include corneal abras
graft, dry eyes, neurotrophic keratitis (absence of normal sensation), and ex
comatose patients in the intensive care unit).
be placed in broth.
with cefazolin (50 mg/ml) plus fortified gentamicin or tobramycin (14 mg/ml
most eyedrops used to treat keratitis must be made up by the hospital phar
are exceptions). These are listed in Table 8-3 . Antibiotic drops can be tailo
when culture results are known. Drops must be given every hour. Patients w
(Ciloxan)2
3 mg/ml
Gentamicin
14 mg/ml
Ofloxacin (Ocuflox)2
3 mg/ml
Penicillin G
100,000 units/ml
Sulfacetamide2
10%, 15%, 30%
Ticarcillin
6 mg/ml
Tobramycin
14 mg/ml
Vancomycin
14 or 25 mg/ml
Concentration1
INTERSTITIAL
KERATITIS
VIRAL
1.
KERATITIS
HERPES
SIMPLEX
KERATITIS
Herpes simplex virus is the most common cause of keratitis in the United S
cases per year. Most cases are from reactivation of latent infection, acquired
subclinical primary ocular or orofacial infection. Herpes simplex virus type 1
ocular infections in adults, whereas type 2 is the major cause in neonates.
2.
HERPES
ZOSTER
KERATITIS
2 y. Each recurrence ca
corneal scarring. Althoug
are helpful in treating s
decreases recurrences o
PARASITIC
1.
KERATITIS
ACANTHAMOEBA
KERATITIS
clinical findings and a ring corneal infiltrate. Symptoms may be chronic, wit
while the patient is mistakenly treated for presumed herpes keratitis.
Diagnosis may be difficult. A calcofluor white stain of corneal scrapings may
2.
ONCHOCERCIASIS
FUNGAL
KERATITIS
Fungal infections of the cornea cause < 2% of corneal ulcers in this country,
treat. Infections caused by molds are more common in the southern United
agricultural workers. On examination, one sees a gray, plaquelike infiltrate w
satellite lesions. Fusarium and Aspergillus spp. are the most common molds
with topical natamycin or amphotericin.
P.94
ENDOPHTHALMITIS
Essentials
Eye
of
Diagnosis
discomfort.
Decreased
vision.
Hypopyon.
Hazy or no view of retina.
No fever or leukocytosis.
General
Considerations
Endophthalmitis means infection within the eye and specifically the vitreous
vitreous is a gel-like substance that fills the posterior segment of the eye (vo
present at birth and becomes liquified with age. It is not reformed once rem
replaced by saline, oil, etc.
There are four major predisposing factors for endophthalmitis: cataract surge
filtering bleb for glaucoma, penetrating eye trauma, and bacteremia.
POSTCATARACT
ENDOPHTHALMITIS
BLEB-RELATED
ENDOPHTHALMITIS
POST-TRAUMATIC
ENDOPHTHALMITIS
ENDOGENOUS
ENDOPHTHALMITIS
Endogenous endophthalmitis means that bacteria (or fungi) have seeded the
bloodstream. Endocarditis is the major risk factor, but cases have occurred
tract/kidney infections, abdominal abscesses, cellulitis, and meningitis and e
gastrointestinal
endoscopy. S aureus and streptococci account for ~50% of
be treated with intravitreal as well as IV antibiotics.
fluconazole (assuming normal renal function, 400 mg orally every day if the
sensitive).
Diagnosis
Treatment
All patients should have antibiotics injected into the vitreous as soon as the
taken (Box 8-2 ). All patients should receive intravitreal vancomycin (1 mg in
amikacin (0.4 mg in 0.1 ml) or ceftazidime (2.25 mg in 0.1 ml). Amikacin is
the least amount of retinal toxicity of the aminoglycosides, although a rare
intravitreal aminoglycoside is macular infarction and loss of vision.
Study) concluded that systemic antibiotics did not affect outcome in postca
although the study was criticized because the antibiotics used (ceftazidime a
activity against coagulase-negative staphylococci, the major pathogens. Van
The need for a vitrectomy to debride the vitreous (vs a vitreous asp
controversial. In the Endophthalmitis Vitrectomy Study of postcataract end
who presented with severe loss of vision (light perception only)
vitrectomy than with vitreous aspirate. This difference was not
with a milder loss of vision. There were potentially confounding
vitreous aspirate group could have a subsequent vitrectomy and
had a better
apparent for
factors, how
still be coun
group).
until culture results are known. Therapy may be stopped then if the eye is i
are negative or reveal coagulase-negative staphylococci. For more virulent o
510 d of systemic therapy. Repeat
P.96
intraocular injections of vancomycin or ceftazidime (depending on the organi
after the first 48 h, because antibiotic levels in the vitreous fall 2448 h
Post
cataract
Coagulase-negative
staphylococci
Staphylococcus
aureus (10%)
Streptococci (10%)
(70%)
Post-traumatic
Bacillus cereus
Coagulase-negative
staphylococci
Same
Endogenous
S aureus
Streptococci
Escherichia coli
Same
1 The need for systemic antibiotics in treating post cataract endophthalmitis
text).
Type
of
Endophthalmitis
Common
Organisms
Empiric
Antibiotic
UVEITIS
Essentials
&
RETINITIS
of
Diagnosis
In anterior uveitis, the conjunctiva is often injected (red) near the limbu
General
Considerations
The eye is made up of three coats: (1) the outer coat is composed of sclera
middle coat is composed of the uvea (choroid, ciliary body, and iris); and (3)
composed of the retina (see Figure 8-6 ). Uveitis is an inflammation of the
The term usually includes retinitis as well, because the retina is often involve
inflammation of the underlying choroid (a part of the uvea). Uveitis affects 1
ANTERIOR
UVEITIS
In anterior uveitis, the iris (iritis) or iris plus ciliary body (iridocyclitis) is inv
eye pain, photophobia, a red eye, and usually decreased vision. A slit lamp
in the anterior chamber; some may coalesce on the back of the cornea (
precipitates).
Of all anterior uveitis cases, ~10% have a known infectious etiology (eg, he
syphilis, Lyme disease, or mycobacteria). The eye findings will regress when
is treated. The remaining ~90% of cases are idiopathic or autoimmune (eg,
Reiter's disease, or systemic lupus erythematosus).
POSTERIOR
UVEITIS
Unlike anterior uveitis, posterior uveitis usually produces no pain. The main
visual loss. Both choroid and overlying retina are usually involved (choriore
1.
TOXOPLASMA
2.
CANDIDA
SPECIES
Although Candida spp. may cause endophthalmitis, they more typically caus
fluffy white lesions seen on funduscopic examination. Treatment is with oral
orally every day) if the Candida species is sensitive.
3.
SYPHILIS
Syphilis may cause almost any retinal appearance, but typically produces a
negative. Ocular syphilis may also result from congenital infection. Any patie
should have a lumbar puncture (to exclude neurosyphilis), as well as a test
immunodeficiency virus [HIV (there is a higher incidence of ocular syphilis in
infection)]. Treatment consists of high-dose IV penicillin (4 million U every 4
renal
function).
4.
TUBERCULOSIS
5.
CYTOMEGALOVIRUS
P.97
occurs in immunosuppressed patients and, until recently, occurred in 204
AIDS. The incidence is now much lower, owing to highly active antiretroviral
appearance is of retinal hemorrhages (red) and exudates
fire appearance. Unlike toxoplasmosis, CMV does not
so the view of the retina is clear. Diagnosis is by clinical
helpful only if negative, although patients with advanced
REFERENCES
Eyelid
Infections
Bajart AM: Lid inflammations. In Albert DM, Jakobiec FA: Principles and Pra
Lacrimal
System
Infections
Lavrich JB, Nelson LB: Disorders of the lacrimal system apparatus. Pediatr
1993;40:767.
Orbital
Infections
Barone SR, Aiuto LT: Periorbital and orbital cellulitis in the Haemophilus
Conjunctivitis
Keratitis
therapy had a higher risk of requiring corneal transplant than those in who
appropriate ([73% vs 20%, respectively].)
Endophthalmitis
Ophthalmology
1997;104:986.
Okada AA, Johnson RP, Liles WC, et al: Endogenous bacterial endophthalmi
year retrospective study. Ophthalmology 1994;101:832.
Uveitis
&
Retinitis
Springer
immunodeficiency
virus-infected
patients.
Infect
Dis
1998;177:10
2001
McGraw-Hill
Respiratory
Tract
Infections
9
Upper Respiratory
Infections
Tract
Abinash Virk MD
Nancy K. Henry PhD, MD
of
Diagnosis
General
Considerations
Clinical
Findings
More
Frequent
Frequent
Epstein-Barr virus
Cytomegalovirus
BOX 9-1 Microbiology of the Common Cold
Differential
Diagnosis
Complications
A complication of the common cold is viral or bacterial sinusitis.
A common cold CT scan study by Gwaltney et al (1994) showed
that sinus involvement occurs in >60% of patients with a cold,
with 79% of these resolving spontaneously in 2 wk without
antibiotics. However, bacterial superinfections of the sinuses,
middle ear, or both are potential complications. Viral pneumonia
or worsening of bronchospastic airway disease is seen,
particularly in children or immunocompromised hosts.
Treatment
The old idiom of prevention is better than cure is
certainly true for the treatment of the common cold. Multiple
different viruses, their many serotypes, and rapid mutations
pose a considerable challenge in the development of one
vaccine or drug for cold prevention or treatment. Symptomatic
Prevention
&
Control
PHARYNGITIS
Essentials
of
Diagnosis
General
Considerations
enterocolitica,
Arcanobacterium
hemolyticum , and
Frequent
Streptococcus
pyogenes (GAS)
Adenovirus
Rhinovirus
Enterovirus
Influenza a/b
Parainfluenza virus
Respiratory syncytial virus
Coxsackievirus
(herpangina)
S pyogenes (GAS)
Adenovirus
Rhinovirus
Enterovirus
Epstein-Barr virus
Mycoplasma
pneumoniae
Chlamydia
pneumoniae
Influenza a/b
Cytomegalovirus
Less
Frequent
Arcanobacterium
hemolyticum
Non-group A streptococci
Yersinia
enterocolitica
Herpes simplex virus
Fusarium tularensis
HIV
Herpes simplex virus
Anaerobic
pharyngitis
Non-group A streptococci
Yersinia
enterocolitica
Neisseria
gonorrhoeae
F tularensis
Children
Adults
Clinical
Findings
Differential
Diagnosis
agranulocytosis,
or
connective-tissue
disorders.
Complications
Local
complications
of
bacterial
pharyngitis
include
peritonsillar
respiratory
tract.
Treatment
In patients with a clinical picture consistent with GAS
pharyngitis, empirical therapy should be started to prevent
suppurative and nonsuppurative complications, to decrease
infectivity and transmissibility, and to induce clinical
improvement of symptoms (Box 9-3 ). Patients with a high
index of suspicion for GAS pharyngitis but negative or pending
RADT/culture results can be given empirical antibiotics until the
results are available. An alternative approach is to withhold
antibiotics until the culture is positive for S pyogenes. Delaying
therapy against GAS does not increase the incidence of
rheumatic heart disease or recurrences with the same strain of
S pyogenes. Following the latter course will decrease
inappropriate antibiotic use and control the increase in antibiotic
resistance.
Antibiotic selection is based on efficacy, ease of administration,
simplex
ulcers,
particularly
P.103
First
Choice
Choice
Allergic
Adults
or
surgical
management.
Prognosis
Uncomplicated pharyngitis results in no sequelae. Prognosis of
GAS pharyngitis complicated by rheumatic heart disease or
poststreptococcal glomerulonephritis is good with penicillin
prophylaxis in rheumatic heart disease and spontaneous
remission in poststreptococcal glomerulonephritis. Suppurative
complications have minimal long-term adverse effects.
Prevention
&
Control
Measures
ACUTE
LARYNGITIS
Essentials
of
Diagnosis
viral,
occasionally
bacterial.
General
Considerations
Clinical
capsulatum,
Findings
Differential
Diagnosis
Complications
Respiratory obstruction in children is the most serious
complication.
P.104
Treatment
Because the majority of laryngeal infections are viral, therapy is
mostly supportive with voice rest, warm saline gargles, and
increased humidity. If specific microbiologic diagnosis is made
with positive microbiologic cultures, then therapy should be
directed at the organism isolated.
Prognosis
Long-term prognosis is excellent with no residual symptoms.
Prevention
&
Control
ACUTE
LARYNGOTRACHEOBRONCHITIS
(CROUP)
Essentials
of
Diagnosis
stridor.
General
Considerations
Clinical
Findings
More
Frequent
Frequent
Adenovirus
Rhinovirus
Enterovirus
Mycoplasma
pneumoniae
Staphylococcus
aureus
Haemophilus
influenzae
Measles virus
S aureus
H influenzae
Fungal-Candida,
Children
Aspergillus spp.
Adults
Differential
Diagnosis
Complications
Severe croup, as may occur with influenza type A, may require
tracheotomy or intubation in 13% of patients and have an
associated mortality of 02.7%. A small percentage of
children with prolonged intubation or severe disease may
develop subglottic stenosis. A few follow-up studies have shown
an increase in hyperactive airways in children with a history of
croup.
Treatment
Antibiotics are not routinely recommended for the
P.106
treatment of croup unless the patient has symptoms or cultures
suggestive of bacterial etiology (Box 9-6 ). Cool air
humidification and supportive care are essential to keep the
child calm, to prevent further tachypnea and distress.
Respiratory rate is the best predictor of hypoxemia. Noninvasive
pulse oximetry or arterial blood gas testing for PaO2 or PaCO2
should aid in assessment of the patient's condition and response
to therapy. Noninvasive monitoring is preferred to prevent
further anxiety in the child.
evaluation.
Prognosis
Croup is mostly a self-limited disease with complete
uncomplicated resolution. As mentioned above, some children
may develop hyperactive airways or become predisposed to
recurrent croup. A few may develop subglottic stenosis caused
by severe disease or prolonged intubation.
Prevention
&
Control
ACUTE
EPIGLOTTITIS
Essentials
of
Diagnosis
General
Considerations
Frequent
Haemophilus
influenzae type b
Staphylococcus
aureus
Streptococcus
pneumoniae
Streptococcus
Less
pyogenes
Frequent
Non-group
streptococci
Clinical
Findings
Signs and Symptoms. The child presents with a short (6to 12-h) rapidly progressive febrile illness, sore throat, pain
on swallowing, and shortness of breath. There is usually no
antecedent history of a viral infection. Adults have a similar
clinical presentation with sore throat being a predominant
symptom.
The patient looks anxious, appears toxic, and assumes a
forward-leaning, neck-extended posture. Drooling of oral
secretions and muffled voice are the sine qua non. The child
has marked tachypnea and may have an inspiratory stridor
Differential
Diagnosis
Complications
Mortality associated with untreated obstructive acute epiglottitis
is ~80%. Respiratory failure from upper-airway obstruction is
the most common complication. Occasionally patients will
develop pulmonary edema along with the respiratory distress.
Treatment
Acute epiglottitis is a medical emergency. Once acute
epiglottitis.
cannot be
tracheotomy. All
be intubated
P.108
Prognosis
Expeditious diagnosis, immediate management of upper-airway
obstruction, and institution of antibiotics decreases morbidity
and mortality related to acute epiglottitis. Full recovery without
sequelae is expected in such patients.
Prevention
&
Control
Choice
Choice
Ampicillin/sulbactam,
100200
mg
ampicillin/kg/d
IV
divided every 6 h
Ampicillin/sulbactam, 1.53.0 g IV every 6 h
Penicillin
Allergic
Adults
Prophylactic
Measures
OTITIS
MEDIA
Essentials
of
Diagnosis
General
Considerations
Frequent
Streptococcus
pneumoniae
Haemophilus
influenzae non-typeable
Moraxella
catarrhalis
Less
Frequent
S aureus
GroupA streptococci
Pseudomonas
aeruginosa
BOX 9-10 Microbiology of Acute Otitis Media
Clinical
Findings
examination
reveals
an
erythematous
tympanic
Differential
Diagnosis
Complications
Chronic otitis media, effusion, mastoiditis, and intracranial
extension may result from recurrent otitis media and persistent
middle ear effusion. In the preantibiotic era, mastoiditis and
intracranial extension occurred in ~20% and 2.5%,
respectively, of AOM patients. Now that the use of antibiotics is
common,
P.110
these rates have decreased to 2.8% and 0.13%, respectively.
Contiguous spread to the cranial fossae, temporal or petrous
bone, or sigmoid or lateral sinuses results in suppurative
complications. Conductive hearing loss because of chronic otitis
media and effusion can potentially impair language development
and academic functioning of the child.
Treatment
A large number of AOM cases are viral in nature with or without
bacterial superinfection. Approximately 30% of AOM cases are
bacterial. Studies have also demonstrated spontaneous
Choice
Choice
Allergic
double-strength
orally
every 12 h
Erythromycin stearate, 250500 mg every 6 h
Prophylaxis
Amoxicillin, 20 mg/kg/d 36 mo
Sulfisoxazole, 50 mg/kg/d 36 months
Chidren
Adults
Prognosis
Recurrent AOM or OME may impair hearing, language
development, and learning capabilities of the patient. The
prognosis is worsened in patients with intracranial extension of
infection. Uncomplicated AOM resolves without significant
sequelae.
Prevention
&
Control
OTITIS
EXTERNA
Essentials
of
Diagnosis
General
Considerations
Clinical
Findings
symptom.
The white
elevated in
or involved
positive for
More
Frequent
Staphylococus
aureus
Group A Streptococcus
Pseudomonas
aeruginosa (swimmer's ear)
Aspergillus
Less
Frequent
Pseudomonas
Complications
Complications develop by local invasion such as temporal bone
osteomyelitis, septic thrombophlebitis of the sigmoid or lateral
sinus or jugular bulb, cranial nerve palsies, meningitis, or brain
abscess.
Treatment
Gentle cleaning is recommended for most otitis externa. Local
heat, topical antibiotic solutions such as neomycin, polymyxin,
or ofloxacin, or systemic antibiotics, or some combination of
these are effective in the treatment of acute otitis externa (Box
9-13 ). Irrigation with hypertonic (3%) saline and cleansing
with alcohol and acetic acid mixed 1:1 are recommended for
acute diffuse otitis externa, whether it is bacterial or fungal.
Fungal otitis externa may also be amenable to treatment with m
-cresyl acetate. Topical antibiotics combined with steroids are
sometimes used for 12 d to decrease edema. Severe
infections may require systemic antibiotics with activity against
P aeruginosa. Malignant otitis externa may be treated with
parenteral antipseudomonal antibiotics such as ceftazidime or
penicillins with antipseudomonal activity such as piperacillin
with aminoglycoside or oral antipseudomonal antibiotics such as
the fluoroquinolones. Topical antipseudomonal antibiotics, such
as neomycin, polymyxin, or ofloxacin, are used for 46 wk.
First Choice
Hypertonic(3%) saline plus alcohol:acetic acid (1:1)
Same
Second Choice
Topical neomycin, polymyxin, or quinolone
Same
Penicillin
Allergic
Topical neomycin, polymyxin, or quinolone
Same
Children
Adults
ACUTE
&
Essentials
CHRONIC
of
SINUSITIS
Diagnosis
General
Considerations
Frequent
Streptococcus
pneumoniae
Haemophilus
influenzae
Moraxella
catarrhalis
Virusesrhinovirus, adenovirus,
cytomegalovirus
Anaerobessuch
Fusobacterium
Staphylococcus
Pseudomonas
Streptococcus
influenza
virus,
Staphylococcus species
P aeruginosa
Viridans
streptococcal
S pneumoniae
Gram-negative
bacilli
Frequent
S aureus
Alpha- and
beta-hemolytic Streptococcus
Gram-negative
bacilliP aeruginosa
FungiAspergillus, Mucor spp.
FungiAspergillus spp.
H influenzae
M
catarrhalis
Mycobacterium
avium complex
Cytomegalovirus
H influenzae
Aspergillus spp.
H influenzae
M catarrhalis
CommunityAcquired
Acute
Sinusitis
Chronic
Sinusitis
Sinusitis in
HIVPositive
Patients
Nosocomial
Sinusitis
Clinical
Findings
Laboratory
Findings. Acute sinusitis is usually associated
with leukocytosis of >10,000 cells/mm3 . The sedimentation
rate may be elevated. Cultures obtained by sinus puncture
are regarded as the standard for an accurate microbiologic
diagnosis and yield bacteria in ~60% of cases. Bacterial
growth of >105 colony-forming units (CFU)/mL suggests an
etiologic role of those specific bacteria whereas growth of <
1 05 CFU/mL may represent contamination. Sinus puncture is
recommended in patients who are severely ill; have
intracranial or orbital complications, compromised immune
systems, nosocomial sinusitis; or are not responding to
standard empirical therapy. Newer endoscopic methods of
collection of secretions are technically more difficult than
puncture, especially from the maxillary antrum because of
the location of its ostium. Endoscopic cultures obtained from
the middle meatus may be contaminated with nasal
secretions.
In
comparison
P.115
catarrhalis.
with
Differential
meningitis.
Diagnosis
Complications
The proximity of the orbits to the sinuses accounts for orbital
complications. Orbital complications include periocular edema,
orbital cellulitis, abscess, and further extension into the
cavernous sinus leading to cavernous sinus thrombosis.
Infection of the bone by direct spread or septic thrombophlebitis
may occur. Frontal bone osteomyelitis and subperiosteal
abscess cause a swelling and doughy feeling of the frontal bone
called Pott's puffy tumor. Intracranial extension results in
meningitis or epidural, subdural, or brain abscess. The incidence
of these complications has declined, but they present as medical
emergencies and require immediate attention. Cough or
bronchitis from aspiration of postnasal drainage into the
respiratory tract may also occur.
Treatment
Therapy of acute bacterial sinusitis includes symptomatic care
along with an appropriate antibiotic regimen (Box 9-15 ). It may
be helpful to stratify patients by the severity of symptoms.
antibiotics
include
macrolides
such
as
clarithromycin
Choice
Amoxicillin/clavulanate, 40 mg
divided every 8 h for 10 d
amoxicillin/kg/d
orally
30
mg/kg/d
Choice
Allergic
Trimethoprim/sulfamethoxa-zole
mg
TMP/kg/d
divided
every 12 h
Erythromycin/sulfisoxazole, 50 mg erythromycin/kg/d and
150 mg sulfisoxazole/kg/d divided every 6 h (max 2 g of
erythromycin and 6 g sulfisoxazole)
Azithromycinor clarithromycin (see above dosing)
Trimethoprim/sulfamethoxazole, double-strength 1 orally
every 12 h
Azithromycin, 500 mg first day, then 250 mg every 24 h for
4 d
Clarithromycin, 500 mg every 12 h
Levofloxacin, 500 mg every 24 h
Clindamycin, 450mg every 8 h
Children
Adults
Prognosis
Most community-acquired bacterial sinusitis episodes respond
well to antimicrobial therapy. Complicated sinusitis or sinusitis
in an immunocompromised host may require aggressive
treatment including surgery. Such patients may continue to
have recurrences and the attendant morbidity. Mortality in
sinusitis is related mostly to complications such as meningitis.
Prophylactic
Measures
Prevention
&
Control
REFERENCES
Adderson EE: Preventing otitis media: medical approaches.
Pediatr Ann 1998;27:101.
1996;25:249.
1995;10:3.
1994;26:1.
1994;73:639.
Livingstone,
1995.
2001
McGraw-Hill
&
Lower
Respiratory
Tract
Infections
10
Tracheobronchitis & Lower
Respiratory Tract Infections
Abinash Virk MD
Walter R. Wilson MD
ACUTE
BRONCHITIS
Essentials
of
Diagnosis
occasionally
General
mechanical
ventilation.
Considerations
Clinical
Findings
More
Frequent
Respiratory syncytial
Adenovirus
Rhinovirus
virus
Parainfluenza virus
Enterovirus
Influenza A/B
Influenza
A/B
Adenovirus
Rhinovirus
Parainfluenza virus
Respiratory syncytial
virus
Enterovirus
Less
Frequent
Streptococcus
pneumoniae
Haemophilus
influenzae
Chlamydia
pneumoniae
Mycoplasma
pneumoniae
Bordetella
pertussis
Streptococcus
pneumoniae
Haemophilus
influenzae
Mycoplasma
pneumoniae
Chlamydia
pneumoniae
Bordetella
pertussis
Children
Adults
Differential
Diagnosis
Complications
Most episodes of acute bronchitis resolve spontaneously.
However, patients with underlying chronic cardiopulmonary
diseases, such as chronic obstructive lung disease (COPD),
congestive heart failure, or severe immunosuppression, may
develop respiratory compromise that requires hospitalization and,
in severe cases, mechanical ventilation. Cough in otherwise
healthy persons may persist for 68 weeks because of
increased airway reactivity.
Treatment
Because acute bronchitis is most often a viral infection, the
majority of the episodes of community-acquired acute bronchitis
require only symptomatic therapy and do not need antibiotic
therapy. Nonetheless, studies have shown that 66% of patients
with acute bronchitis are prescribed antibiotics for this selflimited disease. Antibiotic therapy for acute bronchitis should be
reserved only for select patients, including the elderly, those
with underlying cardiopulmonary disease and persistent cough
(lasting >710 days), or immunocompromised patients. The
choice of antibiotics in such patients should be directed against S
pneumoniae, H influenzae, Mycoplasma spp., or C pneumoniae.
Antibiotics that can be administered on an outpatient basis and
adequately cover these organisms include newer-generation
macrolides such as clarithromycin, azithromycin, and doxycycline
or a fluoroquinolone such as levofloxacin, administered for a 7to 10-day course (Box 10-2 ). Hospitalized patients with acute
bronchitis warrant antimicrobial therapy more often than do
ambulatory patients. The choice of empiric antimicrobial therapy
is the same for outpatients and inpatients.
Symptomatic therapy includes cough suppressants, adequate
hydration, and antipyretics as necessary. Occasionally, patients
may require -adrenergic bronchodilators such as albuterol
inhalers for bronchospasm associated with acute bronchitis.
Prognosis
Prognosis for patients with acute bronchitis is excellent.
Morbidity and mortality are higher among patients with an
underlying
comorbid
condition.
Prevention
Hand washing is an important measure in preventing the
acquisition of viruses that cause viral lower respiratory tract
infections (LRTIs) (Box 10-3 ). Care
P.120
P.121
must also be taken in handling fomites from a person who is ill.
Annual administration of influenza A/B vaccine is important for
the prevention of influenza virus infection. Amantadine or
rimantadine should be administered to exposed nonimmunized
Choice
No antibiotics
Fluids
No antibiotics
Fluids and symptomatic therapy
Second
Choice
mg/kg/d
OR
Trimethoprim/sulfamethoxazole, 8 mg/kg/d orally, divided
every 12 h
OR
Cefpodoxime, 10 mg/d orally, divided every 12 h or other
second- or third-generation oral cephalosporin in equivalent
doses for 10 d
Azithromycin, 500 mg orally on day 1, then 250 mg per day
for 4 d
OR
Clarithromycin 500 mg orally every 12 h for 10 d
OR
oral
cephalosporin
in
equivalent
doses
Allergic
mg/kg/d
orally,
divided
Adults
Prophylactic
Measures
CHRONIC BRONCHITIS
EXACERBATIONS
Essentials
of
&
ACUTE
Diagnosis
General
Considerations
Frequent
Influenza A/B
Parainfluenza
Adenovirus
Streptococcus
Haemophilus
Mycoplasma
Less
virus
virus
pneumoniae
influenzae
catarrhalis
Frequent
Chlamydia
pneumoniae
Gram-negative
bacilli
BOX 10-4 Microbiology of Acute Exacerbation of Chronic
Bronchitis
Sputum may be chronically colonized with Haemophilus spp., S
Clinical
Findings
Differential
Diagnosis
Complications
Repeated attacks of chronic bronchitis can lead to right-heart
failure or cor pulmonale. In acute cases, patients with minimal
pulmonary reserve may develop respiratory failure that requires
mechanical ventilation. Mechanical ventilation is required for
2060% of hospitalized patients with AECB.
Treatment
Management of chronic bronchitis can be divided into two broad
categoriessymptomatic
and
antimicrobial
therapy.
Symptomatic
Therapy. Symptomatic therapy is directed
toward smoking cessation measures and management of
airway secretions and bronchospasm. Smoking cessation
decreases the continual
P.123
irritation of the epithelial lining, thereby decreasing mucus
production within weeks of stopping.
Airway management includes clearance of secretions and use
of bronchodilators. Secretions may be tenacious and difficult
to clear. A good cough is the best mechanism for clearing
secretions. Mobilization of secretions can be increased by the
production.
Prognosis
Advanced age (>65 years), presence of other underlying diseases
such as cardiac disease, multiple previous episodes of AECB,
especially those requiring steroids, and severity of underlying
COPD are poor prognostic factors. The mortality of hospitalized
patients with AECB is ~1030%.
Prevention
Smoking cessation is the most important factor in prevention of
AECB (Box 10-6 ). Patients should be immunized with influenza
vaccine and the 23 polyvalent pneumococcal vaccine.
First
Choice
every 12 h
Levofloxacin, 500 mg IV or orally every 24 h for 1014 d or
another fluoroquinolone with enhanced activity against
Streptococcus
pneumoniae in equivalent dosages
OR
Amoxicillin/clavulanate, 500 mg orally every 8 h
OR
Cefpodoxime, 200 mg orally every 12 h or other second- or
third-generation oral cephalosporins in equivalent doses for
10 d
OR
Trimethoprim/sulfamethoxazole 1 DS tablet orally every 12 h
OR
Doxycycline, 100 mg orally or IV every 12 h for 1014 d
Second
Choice
Allergic
OR
Erythromycin, 2040 mg/kg/d orally or IV divided every 8
h for 10 d
OR
Trimethoprim/sulfamethoxazole,
every 12 h
mg/kg/d
orally
divided
Adults
Prophylactic
Measures
Smoking cessation
Active immunization with influenza and the 23 polyvalent
pneumococcal vaccine in high-risk patients
Amantadine or rimantadine for influenza postexposure
prophylaxis
Droplet isolation for hospitalized patients with Mycoplasma
infection, influenza, RSV infection, and parainfluenza
BOX 10-6 Control of Acute Exacerbation of Chronic
Bronchitis
P.124
P.125
BRONCHIOLITIS
Essentials
Inflammation
of
of
Diagnosis
bronchioles.
General
and
patchy
occasional
ventilatory
Considerations
Frequent
Respiratory
syncytial
virus
(RSV)
Parainfluenza virus
Rhinovirus
Adenovirus
Influenza A/B virus
Enterovirus
Influenza A/B virus
Parainfluenza virus
Adenovirus
RSV
Less
Frequent
Mycoplasma
1
pneumoniae
Uncommon in adults.
Children
Adults1
Clinical
Findings
Differential
Diagnosis
Complications
Immediate complications include apneic spells, dehydration,
hypoxia, and respiratory failure. Apnea occurs more frequently
among premature or very young infants. Dehydration results
from diarrhea, anorexia, or repeated coughing spells that cause
vomiting. Mucus plugging, atelectasis, pneumonia, and
ventilation-perfusion mismatch may cause respiratory failure.
Immunocompromised children or those with comorbidities such
as chronic pulmonary or cardiac disease or prematurity are more
likely to develop a severe infection that requires ventilatory
support.
Late complications include an increased tendency to develop
recurrent hyperactive airways. This may occur in as many as
two-thirds of the patients and persist 27 years after the
episode, but this tendency gradually resolves. The risk of this
late complication is less in children with mild disease that does
not require hospitalization.
Treatment
Therapy of bronchiolitis is based on the severity of disease (Box
10-8 ). In mild cases, outpatient management can be initiated
with adequate hydration, feeding, and close follow-up. Children
should be hospitalized if there is a history of underlying disease
or prematurity; they are < 3 months of age; or they have pulse
oximetry of < 93% on room air, apnea, severe dehydration, or
signs of severe respiratory distress.
Choice
No antibiotics
Fluids
Bronchodilators
No antibiotics
Fluids and symptomatic therapy
Second
Choice
17 d
No role for antibiotics unless secondary infection. In that
case:
Cefotaxime, 1 g IV every 8 h or other second-, third-, or
fourth-generation cephalosporin in equivalent doses
OR
Azithromycin, 500 mg orally on day 1, then 250 mg every
day for 4 d
OR
Erythromycin, 500 mg orally every 6 h for 10 d
OR
Clarithromycin, 500 mg orally every 12 h for 10 d
Penicillin
Allergic
Doses provided here are for patients with normal renal function
Children
Adults
Prognosis
Overall, the prognosis of patients with bronchiolitis is good. The
prognosis is worse in an immunocompromised host or in children
with chronic cardiopulmonary diseases. Mortality among
hospitalized infants with RSV bronchiolitis ranges from 0.5% to
1.5%.
Prevention
Children, especially those with high-risk factors, should avoid
contact with individuals with respiratory infections (Box 10-9 ).
The American Academy of Pediatrics recommends the use of RSV
immunoglobulin prophylactic therapy (RSV-IGIV) for patients at
high risk for severe RSV disease. These
P.128
include premature infants (infants with a gestational age < 28
weeks or between 29 and 32 weeks may benefit from RSV-IGIV
therapy until 12 months or 6 months of age, respectively),
children with bronchopulmonary dysplasia who are < 24 months
postnatal age and are currently using oxygen or have used
oxygen within in the last 6 months, or severely
immunocompromised children. RSV-IGIV has been shown to
decrease RSV-related hospitalizations by 4163%. RSV-IGIV is
given monthly at the onset of the RSV season between October
and April. RSV-IGIV is not approved or recommended for children
Measures
PNEUMONIA
Essentials
of
Diagnosis
General
patterns;
false-negative
Considerations
or
and
aspiration
pneumonia.
Nosocomially
pneumonic
process
occurs.
More
Frequent
Respiratory
syncytial
virus
Adenovirus
Enterovirus
Influenza A/B virus
Parainfluenza virus
Streptococcus
pneumoniae
Haemophilus
influenzae
Chlamydia
pneumoniae
Mycoplasma
pneumoniae
Influenza A/B virus
S pneumoniae
H influenzae
Moraxella
catarrhalis
M pneumoniae
C
L
Less
pneumoniae
pneumophila
Frequent
Legionella
pneumophila
Staphylococcus
aureus
Anaerobes
Streptococcus
pyogenes
Staphylococcus
aureus
Anaerobes
Pseudomonas
aeruginosa
Mycobacterium
tuberculosis
Coxiella burnetii
Coccidioides
immitis
Cryptococcus
neoformans
Histoplasma
Children
BOX
More
capsulatum
Adults
10-10
Microbiology of Community-Acquired
Pneumonia
Frequent
species
Enterobacter
species
Ralstonia (Burkholderia) cepacia
Stenotrophomonas
maltophilia
Achromobacter
(Alcaligenes)
xylosoxidans
K pneumoniae
S pneumoniae
H influenzae
S aureus
Less
Frequent
Mycobacteria avium
Aspergillus
species
M
avium
intracellulare
intracellulare
Aspergillus
species
Influenza A/B virus
Children
Adults
More
Frequent
Respiratory
syncytial
virus
Frequent
Legionella
pneumophila
Anaerobes
Aspergillus
species
L pneumophila
Mycobacterium
tuberculosis
Adults
Clinical
Findings
leukopenia.
Thrombocytopenia
P.133
Blastomyces , or
pneumoniae
infection.
from
bronchoscopic
specimens.
involvement,
P.135
Differential
Diagnosis
granulomatous
lung
extrapulmonary
symptoms
Figure
bilateral
10-5.
Miliary
pulmonary
tuberculosis.
Diffuse
reticular-nodular
infiltrates.
Complications
Pleural effusion and empyema are potential complications and
may cause failure to respond to appropriate therapy. Lung
abscess is another suppurative complication that can occur
among patients, particularly after aspiration or in the presence of
a pulmonary structural problem such as a malignancy. Patients
can develop respiratory failure with or without septic shock and
subsequent death. Respiratory failure and shock are more likely
to occur in elderly, diabetic, alcoholic, or immunocompromised
patients. Preexisting pulmonary disease is a risk factor for
respiratory failure and ventilatory support. Young infants with
RSV pneumonia can develop hyperactive airway disease later in
childhood.
Occasionally, P carinii pneumonia is associated with
spontaneous
pneumothorax.
Treatment
Severity of illness and risk factor assessment is essential in
evaluating a patient for outpatient therapy compared with
hospitalization. The presence of coexisting illnesses,
immunosuppression, respiratory rate of >30/min, hypotension,
multilobar involvement, hypoxemia, acidosis, electrolyte
abnormalities, leukopenia (leukocytes < 4.0/mm3 ) or
leukocytosis (leukocytes >20/mm3 ) are indices of severe
pneumonia that warrant hospitalization. This assessment should
be conducted expeditiously, because these patients can progress
rapidly to circulatory collapse and respiratory distress
necessitating mechanical ventilation. They should receive
immediate antimicrobial therapy, because delay in onset of
antimicrobial therapy may increase morbidity and mortality.
Patients with some but not all of the poor prognostic signs may
(cystic
P.138
10-13A , B
Outpatient
therapy. For outpatient empiric therapy of
CAP, a macrolide such as clarithromycin or azithromycin,
a newer fluoroquinolone with enhanced activity against S
pneumoniae such as levofloxacin or gatifloxacin, or a
tetracycline such as doxycycline is appropriate for
pneumococci, H influenzae , and atypical organisms. Oral
amoxicillin, a second-generation oral cephalosporin, or a
macrolide is appropriate for outpatient treatment of CAP
caused by penicillin-susceptible S pneumoniae.
adequate bactericidal
intermediate resistant S
owing to multidrug
a macrolide,
with
fluoroquinolone
or
influenzae or M
catarrhalis.
First
Choice
Choice
Allergic
Note: Doses provided are for persons with normal renal function.
Children
Adults
First
Pneumonia
Choice
Choice
Allergic
OR
Erythromycin 2040 mg/kg/d IV or orally
divided every 8 h for 10 d OR
Clarithromycin 7.5 mg/kg IV or orally
every 12 h
A fluoroquinolone with enhanced activity against S
pneumoniae such as levofloxacin 500 mg orally or IV every
24 h or another fluoroquinolone in equivalent dosages WITH
OR WITHOUT clindamycin 900 mg IV every 8 h
OR
A macrolide such as azithromycin 500 mg orally or IV on day
1, then 250 mg per day for 4 d
Note: Doses provided are for persons with normal renal function.
Children
Adults
First
(Non-ICU)
Choice
Choice
Allergic
Adults
First Choice
No risk factors and mild to moderate NAP :
dosages
OR
Ciprofloxacin, 500 mg orally every 12 h or another
fluoroquinolone with activity against Pseudomonas
aeruginosa
, such as levofloxacin in equivalent doses.
Severe NAP or with risk factors :
Cefepime, 2 g IV every 12 h, or ceftazidime, 2 g IV every 8 h
PLUS EITHER
Gentamicin 36 mg/kg/d IV divided every 8 h or single
daily dosing of 49 mg/kg/d every 24 h
OR
Ciprofloxacin, 500 mg orally every 12 h or other
fluoroquinolones with activity against P aeruginosa such as
levofloxacin in equivalent doses
Second
Choice
Allergic
Adults
First Choice
Early mild disease :
Cefotaxime, 50 mg/kg dose IV every 8 h
OR
Ceftriaxone, 5075 mg/kg/d IV every 24 h
OR
Other second- third-, or fourth-generation parenteral
cephalosporin
OR
Oxacillin, 100200 mg/kg divided every 6 h IV (maximum,
12 g/d) or other antistaphylococcal penicillin in equivalent
doses
Advanced CF :
Ceftazidime, 3050 mg/kg IV every 8 h (maximum, 6 g/d)
OR
Cefepime, 50 mg/kg IV every 12 h;
PLUS
Gentamicin, 615 mg/kg/d IV divided every 8 h, peak
gentamicin levels of 710 g/mL and trough of
12g/mL, or tobramycin, 67.5 mg/kg/d IV divided
equally every 8 h
Early mild disease :
Cefotaxime, 1 g IV every 8 h
OR
Ceftriaxone, 1 g IV every 24 h
OR
Other second-, third-, or fourth-generation parenteral
cephalosporin
Advanced CF :
Ceftazidime, 2 g IV every 8 h, or cefepime, 2 g IV every 12 h
PLUS
Gentamicin, 615 mg/kg/d IV divided every 8 h, with peak
Choice
Allergic
function.
Children
Adults
Prognosis
Pneumonia is associated with an average mortality rate of 14%
in hospitalized patients and an estimated mortality of < 1% in
nonhospitalized patients. Mortality from pneumococcal
pneumonia among patients >60 years of age varies from 5% to
25% and is ~20% in bacteremic pneumococcal pneumonia. It is
the sixth most common cause of death in the United States. Risk
factors for increased mortality include extremes of age and
underlying diseases such as malignancy, diabetes, chronic lung
disease, chronic renal failure, alcoholism, immunosuppression,
congestive heart failure, and neurological disease. Previous
episodes of pneumonia contribute to higher mortality. Gramnegative bacilli, S aureus , or polymicrobial pneumonia, as in
aspiration or postobstructive pneumonia, are associated with a
higher mortality. Asplenia and severe malnutrition are also
associated with a high mortality.
Prevention
Community-Acquired
Pneumonia. Immunization with the
influenza A/B, 23 polyvalent pneumococcal, and H influenzae
type B vaccines decreases the incidence of infections caused
Prophylactic
Measures
Smoking cessation
Active immunization for influenza A/B for all persons > 50 y
of age
Amantadine or rimantadine for influenza postexposure
prophylaxis
Active immunization with 23 polyvalent pneumococcal
vaccine
Prophylactic
Measures
equipment
Prophylactic
Measures
PARAPNEUMONIC EFFUSION
PLEURAL
EMPYEMA
&
Essentials
of
Diagnosis
breath
sounds.
General
Considerations
Frequent
Staphylococcus
Streptococcus
Haemophilus
Streptococcus
aureus
pneumoniae
influenzae
pyogenes
S aureus
S pneumoniae
S pyogenes
H influenzae
Anaerobes
Less
Frequent
Mycobacterium
Anaerobes
tuberculosis
Pseudomonas
aeruginosa
M tuberculosis
Coccidioides
immitis
Coxiella burnetii
Children
Adults
Clinical
Findings
empyema. Detection
esophageal rupture.
by the presence of
that appears cloudy
Differential
Diagnosis
Complications
In children, empyema may result in pneumatoceles,
pneumothorax, or scoliosis as a result of scarring.
P.148
Other complications result from the local spread of infection to
surrounding structures such as the lung, pericardium, and
myocardium. Some patients develop a severe, overwhelming
infection that results in multisystem organ failure and death.
Empyema-associated mortality is low and varies from 1% to
19%. Mortality increases with age >50 years,
immunosuppression, comorbidities, and NAP.
Treatment
Gross appearance, biochemical composition, and the radiographic
appearance of the fluid guide the management of an infected
effusion. The goals of treatment include appropriate antimicrobial
therapy, removal of infected fluid, and re-expansion of the
underlying lung.
Empiric antimicrobial therapy depends on the putative etiology of
parapneumonic effusion or empyema (Box 10-20 ). When it is the
result of CAP, empiric antimicrobial therapy should be directed
against S pneumoniae , and the use of a third-generation
cephalosporin is appropriate. A specific antimicrobial agent may
be administered for known pathogens recovered from the
sputum, blood, or pleural fluid. Broad-spectrum antimicrobial
therapy is indicated if the empyema is thought to be caused by a
ruptured lung abscess, postobstructive pneumonia from an
endobronchial lesion, postoperative complication, trauma, or a
nosocomial infection. In such situations, therapy should include a
Choice
Choice
Allergic
Doses provided here are for persons with normal renal function
Children
Adults
Prognosis
The prognosis is extremely good, with cure rates of >90% for
uncomplicated parapneumonic effusions when treated with an
appropriate antimicrobial agent and with drainage as necessary.
Patients with loculated pleural effusions or leukocyte counts of <
6400 are associated with treatment failure if not managed with
nonsurgical measures. With the advent of surgical and
nonsurgical intervention techniques and the vast majority of
antimicrobial agents, mortality from empyema is low, ranging
from 4% to 10%. Mortality varies with the causative organisms,
such as Aspergillus species, underlying risk factors such as
malignancy or other comorbid conditions, older age, and delay in
appropriate therapy. Chronic empyema with a thick pleural wall
requires a surgical approach. These types of empyema may take
months to resolve and are more likely to result in treatment
failures.
Prevention
Early administration of effective antimicrobial therapy for LRTIs
and early recognition and drainage of infected parapneumonic
effusions are most important for the prevention of empyema (Box
10-21 ). Careful closure and inspection of the bronchial stump
after pneumonectomy may prevent empyema that results from a
postoperative
bronchopleural
fistula.
LUNG
ABSCESS
Essentials
of
Diagnosis
mostly
anaerobic
microorganisms;
often
Prophylactic
Measures
General
Considerations
abscesses varies by the cause (Box 10is the most common cause, it results in
that includes gram-negative bacilli,
anaerobes. Anaerobes encountered in
Frequent
Staphylococcus
aureus
Group A -hemolytic streptococci
Streptococcus
pneumoniae
Haemophilus
influenzae
Prevotella species
Bacteroides species
Fusobacterium species
Prevotella species
Bacteroides species
Fusobacterium
species
S aureus
Group A -hemolytic streptococci
Klebsiella
pneumoniae
Pseudomonas
aeruginosa
Proteus species
H influenzae
Less
Frequent
Gram-negative
bacilli
(neonates)
Mycobacterium
tuberculosis
Nocardia species
Coccidioides
immitis
Histoplasmosis
M tuberculosis
Nocardia species
Coccidioides
immitis
Histoplasmosis
Rhodococcus equi
Salmonella species
Legionella
pneumophila
Children
Adults
Clinical
Findings
of
unconsciousness.
Differential
immitis .
Diagnosis
Complications
Complications of lung abscess primarily result from direct
extension of infection into neighboring structures. Pleura-based
lung abscesses may extend into the pleural cavity and result in
an empyema, which occurs in about one-third of patients with a
lung abscess. Bronchopleural fistula with resultant
pyopneumothorax may occur. Some abscesses that are in close
proximity to a large pulmonary vessel may erode into the vessel
and cause massive or fatal hemorrhage. Systemic dissemination
of infection to other locations, such as the brain, may occur.
Figure
lesion.
Treatment
The principles of treatment for a lung abscess are the same as
for abscesses elsewhere in the bodyeffective antimicrobial
therapy and drainage.
Initial empiric antibiotic therapy should be directed against
polymicrobial oropharyngeal flora, especially anaerobes (Box 102 3 ). This may be achieved with either a combination of a
parenteral penicillin or a third-generation cephalosporin with
clindamycin or metronidazole; or a -lactam/-lactamase
inhibitor combination such as piperacillin/tazobactam or
ampicillin/sulbactam. Alcoholics, nursing home residents, or
patients with a nosocomially acquired lung abscess should
receive therapy with a third- or fourth-generation cephalosporin
with antipseudomonal activity, such as ceftazidime or cefepime,
together with clindamycin or metronidazole; or a -lactam/lactamase inhibitor combination or a carbapenem (imipenem or
meropenem); or a fluoroquinolone such as levofloxacin or
ciprofloxacin together with clindamycin or metronidazole. The
duration of antibiotic therapy is usually 46 weeks, with
reassessment at intervals for complications or lack of response.
Clinical improvement is usually apparent within 12 weeks;
however, there is a delay of 812 weeks before resolution
of the cavity occurs on chest radiograph or CT scan.
Medical therapy is effective in 8090% of patients with a lung
abscess < 5 cm in diameter. The majority of lung abscesses
spontaneously drain into a
P.152
bronchus. Postural drainage is strongly encouraged, and this may
be improved with chest physiotherapy. Patients who do not
respond to medical therapy or those with enlarging cavity size,
ongoing sepsis, or associated empyema require drainage.
Drainage of the lung abscess can be performed with transthoracic
radiographic guidance or with open surgical drainage. Open
Prognosis
pneumoniae ,
P.153
Choice
Choice
Allergic
Doses provided here are for patients with normal renal function
Children
Adults
Prevention
It is important to identify patients susceptible to aspiration and
to institute aspiration precautions promptly in these patients
(Box 10-24 ). Lung abscess should be suspected in patients with
a slow response or progression of infection despite appropriate
therapy for CAP.
Prophylactic
Measures
diseases
Regular dental visits for good dental hygiene
Avoid alcohol abuse
BOX 10-24 Control of Lung Abscess
P.154
REFERENCES
Anonymous: Palivizumab, a humanized respiratory syncytial
virus monoclonal antibody, reduces hospitalization from
respiratory syncytial virus infection in high-risk infants. The
IMpact-RSV Study Group. Pediatrics 1998;102:531.
Auble TE, Yealy DM, Fine MJ: Assessing prognosis and
selecting an initial site of care for adults with communityacquired pneumonia. Infect Dis Clin North Am 1998;12:741.
Bernstein
JM:
Treatment
pneumoniaIDSA
of
guidelines.
community-acquired
Chest
1999;115:9S.
2001
McGraw-Hill
Endocarditis
11
Infective
Endocarditis
James M. Steckelberg MD
Walter R. Wilson MD
Essentials
of
Diagnosis
General
Considerations
Clinical
Findings
or
conduits
Moderate-risk
category:
Most other congenital cardiac malformations (other than
above and below)
Acquired valvar dysfunction (eg, rheumatic heart
disease)
Hypertrophic
cardiomyopathy
Mitral valve prolapse with valvar regurgitation,
thickened leaflets, or both
Endocarditis prophylaxis not recommended
Negligible-risk category (no greater risk than the general
population):
Isolated secundum atrial septal defect
Surgical repair of atrial septal defect, ventricular septal
defect, or patent ductus arteriosus(without residua beyond 6
mo)
Previous coronary artery bypass graft surgery
Mitral valve prolapse without valvar regurgitation
Physiologic, functional, or innocent heart murmurs
Previous Kawasaki disease without valvar dysfunction
Previous rheumatic fever without valvar dysfunction
Cardiac pacemakers (intravascular and
implanted
defibrillators
1 Source: JAMA 1997; 277:17941801.
Table
epicardial)
and
membranes.
Imaging.
demonstrates
cardiac
valvular
Differential
Diagnosis
Complications
Intracardiac
Complications. Cardiac valvular destruction with
resulting valvular insufficiency and cardiac failure is the most
common intracardiac complication of infective endocarditis.
Valvular dysfunction can occur from perforation of a valve
leaflet, destruction of supporting apparatus such as an infected
ruptured mitral chordae, or dehiscence of a prosthetic valve.
Alternatively, large, bulky vegetations may occasionally result in
valve outflow obstruction mimicking valvular stenosis.
Perivalvular extension of infection with abscess formation is
associated more commonly with S aureus infections, infections
of the aortic valve, and infections of prosthetic valves.
Perivalvular extension may be clinically silent or manifested by
conduction delays, persistent bacteremia or fever on
appropriate therapy, fistulous tracts between cardiac chambers
or the pericardial space, or prosthetic valve dehiscence. As
noted above, transesophageal echocardiography is more
accurate (positive predictive value, 87%; negative predictive
value, 89%) than transthoracic echocardiography for the
detection of perivalvular abscesses. The development of new
atrioventricular block on electrocardiography has 88%
specificity for abscess but poor sensitivity (45%).
Extracardiac
Complications. Arterial emboli occur in
2040% of patients with infective endocarditis. Symptomatic
emboli occur most frequently in the central nervous system;
events occur
be considered in
presents with
Overall, the
Frequent
Frequent
Hemophilus
aphrophilus and related species, Actinobacillus
actinomycetemcomitans,
Cardiobacterium
hominis,
Eikenella
corrodens, and Kingella spp.
Native
Valves
Prosthetic
Valves
endocarditis)
Antiphospholipid
syndrome
Polyarteritis
nodosa
Behet's
disease
Postvalvular
surgery:
Thrombus
Stitch after surgery
Other postvalvular surgery changes
Miscellaneous
Eosinophilic heart disease
Ruptured mitral chordae
Myxomatous
degeneration
1 Source: Berbari & Steckelberg, Mayo Clin Proc 1997; 72:
53242.
Table
Treatment
Effective medical treatment of infective endocarditis requires
identification and susceptibility testing of the responsible
microorganism; sustained bactericidal antimicrobial therapy
singly or in combination, usually in high concentrations, based
on the susceptibility of the microorganism (Tables 11-4 ,11-5
,11-6 ,11-7 ,11-8 and 11-9 ); identification and treatment of
complications, including abscesses and complications of drug
therapy; identification and eradication of the original source of
infection (such as a dental abscess) if possible; and patient
education about future endocarditis antimicrobial prophylaxis
(Tables 11-1 , 11-10 ,11-11 ,11-12 and 11-13 ).
Surgical intervention is necessary in about a third of patients
with endocarditis and is lifesaving in some situations. The most
common indication for valve replacement or valve repair surgery
is congestive heart failure or hemodynamic instability due to
valvular dysfunction that is unresponsive to medical therapy. In
persistent
P.159
Vancomycin therapy is recommended for patients allergic to lactams (see text); peak serum concentrations of vancomycin
should be obtained 1 h after completion of the infusion and
should be in the range of 3045 g/mL for twice-daily dosing
1 Dosages recommended are for patients with normal renal
function. For nutritionally variant streptococci, see Table 11-6 .
IV indicates intravenous; IM, intramuscular.
2
Antibiotic
Dosage and
Route
Duration,
wk
Comments
doses
4
Cefazolin or other first-generation cephalosporins may be
substituted for penicillin in patients whose penicillin
hypersensitivity is not of the immediate type
With gentamicin sulfate2
1 mg/kg IM or IV every 8 h
2
Vancomycin
hydrochloride3
30 mg/kg per 24 h IV in two equally divided doses, not to
exceed 2 g/24 h unless serum levels are monitored
4
Vancomycin therapy is recommended for patients allergic to lactams
1 Dosages recommended are for patients with normal renal
function. IV indicates intravenous; IM, intramuscular.
2 For specific dosing adjustment and issues concerning
gentamicin (obese patients, relative contraindications), see
Table 11-4 footnotes.
3
Antibiotic
Dosage and
Route
Duration,
wk
Comments
Prognosis
As noted above, untreated infective endocarditis is uniformly
fatal. The prognosis with accurate diagnosis and treatment is
highly variable, depending on the
P.160
P.161
P.162
microorganism, the degree of valvular destruction before
antimicrobial treatment, and whether prosthetic material is
involved. In uncomplicated viridans group streptococcal
infection of a native valve, outcome is frequently excellent,
including prompt response of fever and systemic symptoms to
antimicrobial therapy and cure rates exceeding 98% with
approved regimens in patients who survive to complete therapy.
In contrast, mortality in prosthetic valve infection with
staphylococci, gram-negative bacilli, or fungi remains in the
range of 2550%, despite aggressive medical and
surgical therapy.
Aqueous crystalline penicillin G sodium
1830 million U/24 h IV either continuously or in six equally
divided doses
46
With gentamicin sulfate2
1 mg/kg IM or IV every 8 h
46
4-wk therapy recommended for patients with symptoms <3 mo
in duration; 6-wk therapy recommended for patients with >3 mo
in duration
Ampicillin sodium
12 g/24 hIV either continuously or in six equally divided doses
46
With gentamicin sulfate3
1 mg/kg IM or IV every 8 h
46
Vancomycin
hydrochloride2 ,3
30 mg/kg per 24 h IV in two equally divided doses, not to
exceed 2 g/24 h unless serum levels are monitored
46
Vancomycin therapy is recommended for patients allergic to lactams; cephalosporins are not acceptable alternatives for
patients allergic to pencillin
With gentamicin sulfate2
1 mg/kg IM or IV every 8 h
46
1 All enterococci causing endocarditis must be tested for
antimicrobial susceptibility in order to select optimal therapy
(see text).
This table is for endocarditis due to gentamicin- or vancomycinsusceptible enterococci, viridans streptococci with a minimum
inhibitory concentration of >0.5 g/mL, nutritionally variant
viridans streptococci, or prosthetic valve endocarditis caused by
viridans streptococci or Streptococcus
bovis . Antibiotic dosages
are for patients with normal renal function.IV indicates
intravenous; IM, intramuscular.
2 For specific dosing adjustment and issues concerning
gentamicin (obese patients, relative contraindications), see
Table 11-4 footnotes.
3 For specific dosing adjustment and issues concerning
vancomycin (obese patients, length of infusion), see Table 11-4
footnotes.
Reprinted from JAMA 1995; 274:17061713.
Antibiotic
Table
Dosage and
Route
Duration,
wk
Comments
Methicillin-Susceptible
Staphylococci
Regimens for non--lactam-allergic patients
Naficillin sodium or oxacillin sodium
2 g IV every 4 h
46 wk
Benefit of additional aminogly cosides has not been established
With optional addition of gentamicin sulfate2
1 mg/kg IM or IV every 8 h
35 d
Regimens for -lactam-allergic patients
Cefazolin (or other first-generation cephalosporins
dosages)
in
equivalent
2 g IV every 8 h
46 wk
Cephalosporins should be avoided in patients with immediatetype hypersensitivity to penicillin
With optional addition of gentamicin2
1 mg/kg IM or IV every 8 h
36 d
Vancomycin
hydrochloride3
30 mg/kg per 24 h IV in two equally divided doses, not to
exceed 2 g/24 h unless serum levels are monitored
46 wk
Recommended for patients allergic to pencillin
Methicillin-Resistant
Staphylococci
Vancomycin
hydrochloride3
30 mg/kg per 24 h IV in two equally divided doses, not to
exceed 2 g/24 h unless serum levels are monitored
46 wk
1 For treatment of endocarditis due to penicillin-susceptible
staphylococci (minimum inhibitory concentration 0.1
from
Antibiotic
JAMA
1995;
274:17061713.
Duration
Comments
With rifampin3
300 mg orallyevery 8 h
6
And with gentamicin sulfate4 ,5
1.0 mg/kg IM or IV every 8 h
2
Cephalosporins should be avoided in patients with immediatetype hypersensitivity to penicillin or with methicillin-resistant
staphylococci.
1 Dosages recommended are for patients with normal renal
function. IV indicates intravenous; IM, intramuscular.
2 For specific dosing adjustment and issuesconcerning
vancomycin (obese patients, length of infusion), see Table 11-4
footnotes.
3 Rifampin plays a unique role in the eradication of
staphylococcal infection involving prosthetic material (see text);
combination therapy is essential to prevent emergence of
rifampin
resistance.
4 For specific dosing adjustment and issues concerning
gentamicin (obese patients, relative contraindications), see
Table 11-4 footnotes.
5 Use during initial 2 wk.
Reprinted from JAMA 1995;
Antibiotic
274:17061713.
Dosage and
Route
Duration,
wk
Comments
4
With gentamicin sulfate4
1 mg/kg IM or IV every 8 h
4
1
Antibiotic
Dosage and
Route
Duration,
wk
see
Comments
Restorative
dentistry3 (operative and prosthodontic) with or
without retraction cord4
Local anesthetic injections (nonintraligamentary)
Intracanal endodontic treatment; post-placement and
Placement of rubber dams
Postoperative suture removal
Placement of removable prosthodontic or orthodontic
buildup
appliances
Taking of oral impressions
Fluoride
treatments
Taking of oral radiographs
Orthodontic appliance adjustment
Shedding of primary teeth
1 Source: JAMA 1997; 277:17941801.
2 Prophylaxis is recommended for patients with high- and
moderate-risk cardiac conditions.
3
Prostatic
surgery
Cytoscopy
Urethral
dilation
Endocarditis prophylaxis not recommended
Respiratory
tract
Endotracheal
intubation
Bronchoscopy with a flexible bronchoscope, with or without
biopsy3
Tympanostomy tube insertion
Gastrointestinal
tract
Transesophageal
echocardiography3
Endoscopy with or without gastrointestinal
biopsy
Genitourinary
tract
Vaginal
hysterectomy3
Vaginal
delivery3
Cesarean
section
In
uninfected tissue:
Urethral
catheterization
Uterine dilatation and curettage
Therapeutic
abortion
Sterilization
procedures
Insertion or removal of intrauterine devices
Other
Cardiac catheterization, including balloon angioplasty
Implanted cardiac pacemakers, implanted defibrillators,
and coronary stents
Incision or biopsy of surgically scrubbed skin
Circumcision
1 Reprinted with permission from JAMA 1997;
277:17941801.
2 Prophylaxis is recommended for high-risk patients; it is
optional for medium-risk patients.
3 Prophylaxis is optional for high-risk patients.
Table
penicillin
or cephalexin3
mg; children: 20 mg/kg orally 1 h before procedure
g; children: 50 mg/kg orally 1 h before procedure
Azithromycin or clarithromycin
Adults: 500 mg; children: 15 mg/kg orally 1 h before procedure
Allergic to penicillin and unable to take oral medications
Clindamycin
Adults: 600 mg; children: 20 mg/kg IV within 30 min before
procedure
Cefazolin3
Adults: 1.0 g; children: 25 mg/kg IM or IV within 30 min before
procedure
1 Reprinted with permission from JAMA 1997;
277:17941801. Abbreviations: IM, intramuscularly;
intravenously.
IV,
Situation
Agent2
Regimen
Prevention
Patients with known cardiac risk factors for infective
endocarditis should have regular professional dental care and
practice good oral hygiene. The
P.163
American Heart Association recommends specific antimicrobial
prophylaxis for patients who have cardiac abnormalities
associated with increased risk of endocarditis and who are
undergoing certain invasive procedures associated with a risk of
transient bacteremia caused by microorganisms commonly
causing
1 3 ).
High-risk
endocarditis
(Tables
patients
Agent2
Regimen 3
REFERENCES
Dajani AS et al: Prevention of bacterial endocarditis.
Recommendations by the American Heart Association. J Am
Med Assoc 1997;277:1794.
Patel R, Steckelberg JM: Infections of the heart. In Murphy
JG (editor): Mayo Clinic Cardiology Review , Futura
Publishing Co, 1997.
Wilson WR et al: Antibiotic treatment of adults with infective
endocarditis due to streptococci, enterococci, staphylococci,
and HACEK microorganisms. J Am Med Assoc
1995;274:1706.
Wilson WR, Steckelberg JM (editors): Infective endocarditis.
Infect Dis Clin North Am 1993;7.
2001
McGraw-Hill
Infections
12
Intra-abdominal
Infections
ABDOMINAL
PAIN
CLINICAL
SYNDROMES
PERITONITIS
1. SPONTANEOUS
PERITONITIS
Essentials
of
BACTERIAL
Diagnosis
Presence of ascites.
Fever in ~80% of cases.
No symptoms or signs in 30% of patients at presentation.
Abdominal tenderness in only 50% of patients.
Ascitic fluid with >250 neutrophils/mm3 .
Ascitic fluid with >10,000 neutrophils/ mm3 and yielding
>one microorganism by culture, suggests secondary
peritonitis.
General
Considerations
Clinical
Findings
More
Frequent
Streptococcus
pneumoniae
Group A streptococcus
Escherichia coli
Streptococcus
pneumoniae
Less
Frequent
Escherichia
coli
Klebsiella spp.
Anaerobes
Children
Adults
Differential
Diagnosis
Prognosis
The mortality rate of spontaneous bacterial peritonitis in
cirrhotic adults is high, with some studies reporting rates as
high as 95%. The high mortality is mainly due to the
accompanying end-stage cirrhosis, and more recent studies
have reported mortality rates between 57% and 70%.
Treatment
SBP should be treated with broad antimicrobial coverage until
culture results are available. Third-generation cephalosporins,
such as cefotaxime, are recommended, but many other agents,
such as -lactam/-lactamase inhibitor combinations or
carbapenems, are also effective (Box 12-2 ). If SBP develops
during hospitalization, consideration should be given to
antipseudomonal coverage by using an aminoglycoside plus an
antipseudomonal penicillin or cephalosporin. Intravenous
antimicrobial agents should be given for 1014 days. More
recent data indicate that 5 days of therapy may be sufficient in
those patients who are clinically well and in whom the ascitic
fluid is culture negative and the PMN leukocyte count is < 250
cells/mm3 , after this period of therapy.
Typical
spontaneous
bacterial
peritonitis
>250 cells/mm3
Positive
Culture-negative neutrocytic
ascites
>500 cells/mm3
Negative
Monomicrobial
nonneutrocytic
<250 cells/mm3
bacterascites
Positive
Ascitic Fluid PMNs
Table
First
Cultures
Choice
Choice
Ampicillin-sulbactam, 3 g IV every 6 h
OR
Ticarcillin-clavulanate, 3.1 g IV every 46 h
OR
Piperacillin-tazobactam, 4.5 g IV every 8 h
OR
Imipenem-cilastatin, 500 mg IV every 6 h
OR
Clindamycin, 600 mg IV every 8 h plus ciprofloxacin, 400
mg IV every 12 h
Penicillin
Allergic
Clindamycin/cipro-floxacin
Children
Adults
(as
above)
Prevention
Recurrences of SBP occur in >50% of patients within 6 mo of
the initial episode; therefore, prophylaxis is recommended (Box
12-3 ). Agents such as norfloxacin (400 mg/d) or trimethoprimsulfamethoxazole (one double-strength tablet/d) are effective.
These antimicrobial agents have been shown to decrease
significantly the incidence of primary
P.167
peritonitis, but they have not been shown to improve survival.
Preventive
Measures
(1
double-strength
tablet/d)
Precautions
None
BOX 12-3 Prevention of Spontaneous Bacterial
Peritonitis
2.
SECONDARY
Essentials
of
PERITONITIS
Diagnosis
sepsis,
Elevated
General
hypovolemic
peripheral
shock.
leukocyte
count.
Considerations
More
Frequent
As per adults
Bacteroides
fragilis
Peptostreptococcus spp.
Clostridium spp.
Bilophila
wadsworthia
Escherichia coli
Proteus spp.
Klebsiella spp.
Streptococcus spp.
Less
Frequent
Pseudomonas
aeruginosa
Enterococcus spp.
Candida spp.
Children
BOX
12-4
Clinical
Adults
Microbiology of Secondary/Tertiary
Peritonitis
Bacterial
Findings
Laboratory
Findings. As part of the evaluation of a patient
with a suspected intra-abdominal infection, a leukocyte
count, urine analysis, and blood cultures should be
performed.
Imaging. An upright chest x-ray or left lateral decubitus
radiograph may reveal free air (Figure 12-1 ) in 70%
of patients with a perforated gastric or duodenal ulcer, but
will rarely reveal free air with other types of perforated
viscus. Radiologic evaluation of patients with suspected
peritonitis or localized abscess has become invaluable. In
addition, computed-tomography (CT) or ultrasound-guided
aspiration or drainage of a suspected intra-abdominal
abscess has become standard practice in the evaluation and
management of patients. Ultrasonography is usually less
costly than CT; ultrasonography is also usually portable, it
is noninvasive, and it may be obtained rapidly. It is very
useful in the evaluation of gallbladder and biliary tract
disease and is also useful for evaluating the pelvis in a
female patient with signs of pelvic infection, in whom the
pelvic and rectal examinations have not identified the cause.
The weaknesses of ultrasonography include operator
dependency and limitations imposed by bowel gas and fat in
the abdominal wall and omentum. CT with intravenous, oral,
and rectal contrast is the most definitive radiographic test
(Figure 12-2 ). Its strengths include provision of a relatively
complete picture of intraperitoneal and retroperitoneal
anatomy, thereby revealing small or deep fluid collections
and abscesses. CT can also detect and localize causes of
bowel obstruction and detect free air trapped within the
bowel wall better than any other method. Its drawbacks
include the needs for ionizing radiation, intravenous
contrast, and patient cooperation and its lack of portability.
Differential
Diagnosis
Prognosis
Survival in a patient with secondary peritonitis depends on
Treatment
General
Management. Based on the history, physical
examination and initial laboratory data, patients with
secondary peritonitis can usually be placed in one of two
categories: those who should and those who should not
undergo surgery in the next few hours. Those patients who
do not undergo surgery should be observed and evaluated
closely. Patients with ascites should have paracentesis
performed and a PMN leukocyte count, along with bacterial
cultures, obtained. The decision as to the most appropriate
radiographic procedure is then made. Evaluation of each
patient must be individualized and should be based on the
patient's specific presentation. There is no concise set of
infallible guidelines regarding when to order a test and
which test or tests to order for any given patient. The
decision must be made as to the immediacy of investigation
and intra-abdominal exploration or observation.
Surgical intervention is the mainstay of therapy for some
patients and must be performed promptly for peritonitis that
is secondary to bowel perforation or penetrating trauma.
The underlying pathology should be corrected, necrotic
tissue debrided, and further peritoneal seeding by
microorganisms prevented. The duration of antimicrobial
therapy after surgery is usually 57 d, depending on the
severity of the infection, clinical response, and
normalization of the leukocyte count. Although treatment of
are
frequently
under-dosed
because
of
3.
TERTIARY
PERITONITIS
4.
PERITONITIS
COMPLICATING
PERITONEAL
DIALYSIS
Continuous ambulatory peritoneal dialysis (CAPD) was
developed in the late 1970s, and this procedure creates a
special predisposition for the development of peritonitis. The
overall incidence of peritonitis is 1.31.4 episodes/CAPD
patient per year. Organisms
P.171
gain access to the peritoneal cavity in several ways. Most
Choice
Adults
First
Choice
plus
ciprofloxacin
aminoglycoside2
aztreonam
Adults
INTRAPERITONEAL
Essentials
Previous
of
bowel
ABSCESS
Diagnosis
perforation.
General
Considerations
1.
SUBPHRENIC
ABSCESS
Clinical
Findings
Treatment
The primary treatment of a subphrenic abscess is drainage,
either via a percutaneous approach or an open laparotomy.
Antimicrobial therapy is aimed at the likely spectrum of
organisms associated with the presumed pathogenic mechanism
and may be modified after the receipt of culture results. Caution
should be used when assessing culture results from patients
who have already been receiving antimicrobial therapy.
2.
DIVERTICULAR
ABSCESS
3.
VISCERAL
Liver
ABSCESSES
Abscess
Essentials
1530%
of
are
Diagnosis.
cryptogenic.
tenderness.
Peripheral blood leukocytosis is present.
Alkaline phosphatase serum levels are elevated.
CT scan is the diagnostic test of choice.
General
Considerations
cryptogenic.
Clinical
Findings
identification
of E
More
Frequent
As per adult
AND
Staphylococcus
aureus
Escherichia coli
Proteus spp.
Klebsiella spp.
Enterobacter spp.
Streptococci
Less
Frequent
Entamoeba
Children
histolytica
Adults
Differential
Diagnosis
Prognosis
The prognosis of pyogenic liver abscess depends on the rapidity
with which the diagnosis is made and treatment started. Recent
studies have shown
range. The advent
affected treatment,
necessary in every
Pancreatic
Abscess
Essentials
of
Diagnosis
are
polymicrobial.
General
Considerations
pancreatic
inflammatory
mass.
Splenic
Abscess
APPENDICITIS
Clinical
Findings
Differential
Diagnosis
Treatment
Therapy for appendicitis is surgical removal and drainage of any
abscess that may be present. Antibiotics need only be started
CAECITIS
(TYPHLITIS)
Clinical
Findings
this
entity.
Treatment
Mortality rate is high and, although management is
controversial, antimicrobial therapy, as outlined in Boxes 12-5
and 12-6 , together with surgical resection of necrotic bowel, is
generally
recommended.
ACUTE
CHOLECYSTITIS
Clinical
Findings
Complications
Complications include perforation in 1015% of cases. These
patients are readily recognizable because they present with
acute symptoms and signs of diffuse peritonitis.
Differential
Diagnosis
and
Treatment
Antibiotics to treat acute obstructive cholecystitis include those
outlined in Boxes 12-5 and 12-6 . Coverage should be directed
at the organisms already discussed (Box 12-4 ), although
anaerobes play a lesser role in acute cholecystitis. Immediate
surgery should be performed for gangrenous cholecystitis,
perforation, or suspected peri-cholecystic abscess. The timing of
surgery for patients with uncomplicated acute cholecystitis is
controversial.
CHOLANGITIS
Cholangitis is defined as various degrees of inflammation,
infection, or both involving the hepatic and common bile duct.
Clinical
Findings
Complications
Complications of bacteremia and shock occur more commonly in
patients with obstructive cholangitis. Perforation of the
gallbladder can occur leading to hepatic abscess, peritonitis, or
a peri-cholecystic abscess.
Differential
Diagnosis
Treatment
Prompt antimicrobial therapy is mandatory with choices as
outlined in Boxes 12-5 and 12-6 . Prompt operative intervention
with decompression of the common duct is mandatory in most
cases of cholangitis. In those patients who do undergo surgery,
operative cholangiography should be performed.
REFERENCES
Bennion RS et al: The bacteriology of gangrenous and
perforated appendicitis-revisited. Ann Surg 1990;211:165.
Bhuva M et al: Spontaneous bacterial peritonitis: an update
on evaluation, management, and prevention. Am J Med
1994;97:169.
Finegold SM, Wilson SE: Intra-abdominal infections and
abscesses. In Mandell GL, Lorber B: Atlas of Infectious
Diseases , Vol VII. Churchill Livingstone, 1996.
Levison MA: Percutaneous versus open operative drainage of
2001
McGraw-Hill
> Table of Contents > Section II - Clinical Syndromes > 13 Skin & Soft-Tissue Infections
13
Skin & Soft-Tissue Infections
Mark P. Wilhelm MD, FACP
Randall S. Edson MD, FACP
General
Considerations
THE
PYODERMAS
IMPETIGO
Essentials
of
Diagnosis
General
Considerations
Clinical
Findings
Differential
Diagnosis
Complications
Occasionally, infections caused by nephritogenic strains of GAS
can result in poststreptococcal glomerulonephritis. Mentioned in
treatment section.
Treatment
Although impetigo may resolve spontaneously without antiinfective therapy, treatment is generally recommended for more
rapid resolution of established lesions, deterring the formation of
new lesions, preventing evolution to cellulitis, and possibly
preventing the development of post-streptococcal
glomerulonephritis, which occasionally follows infection caused
by nephritogenic GAS strains (Box 13-2 ). Treatment options
include a 10-day course of oral dicloxacillin sodium, a firstgeneration
cephalosporin
P.179
(eg, cephalexin), clindamycin, or topical mupirocin. It has not
been established conclusively that antibacterial therapy is
effective in reducing the incidence of nephritis.
Impetigo
S pyogenes, S aureus
Erysipelas
S pyogenes
S aureus
Ecthyma
S aureus, S pyogenes
P aeruginosa
Cellulitis
S pyogenes, S aureus
H influenzae, P multocida,
Cutaneous abscess
S aureus
Furuncle
S aureus
Enterobacteriaceae,
Aeromonas spp.
Carbuncle
S aureus
Folliculitis
S aureus
P aeruginosa
Syndrome
More
Frequent
Less
Frequent
ERYSIPELAS
Essentials
Edematous,
Sharply
of
red,
Diagnosis
indurated,
demarcated,
spreading
advancing,
lesion.
elevated
margin.
General
Considerations
Clinical
Findings
Differential
Diagnosis
Treatment
In most cases of erysipelas, therapy is initiated with a parenteral
agent active against -hemolytic streptococci such as penicillin
G or cefazolin (see Box 13-2 ). After clinical improvement is
documented, therapy may be switched to an oral agent (eg,
penicillin V or cephalexin). Parenteral therapy may not be
necessary in mild cases with minimal systemic toxicity. Hot packs
applied locally and aspirin are generally administered for
symptomatic
relief.
Prognosis
Skin necrosis does not occur in cases of erysipelas, and healing
is generally complete without scar formation. However,
involvement of superficial lymphatics may result in recurrence of
erysipelas in the same area.
ECTHYMA
Essentials
Punched-out
of
ulcers
Diagnosis
appearing
beneath
adherent
crusts.
General
Considerations
Ecthyma
Dicloxacillin, 500 mg every 6 h, O R cephalexin, 500 mg
every 6 h
For ecthyma gangrenosum caused by P aeruginosa :
piperacillin 34 g IV every 46 h + gentamicin or
tobramycin, 1.5 mg/kg every 8 h O R ceftazidime, 12 gm
IV every 8 h +/- gentamicin or tobramycin
Clindamycin, 150300 mg four times daily
Ciprofloxacin, 400 mg IV or 750 mg orally every 12 h
Cellulitis
Parenteral: nafcillin, 12 g every 46 h, O R cefazolin, 1
g every 8 h
Oral: dicloxacillin, 500 mg four times daily O R
500 mg four times daily
cephalexin,
abscess
Carbuncle
Parenteral: nafcillin, 12 g every 46 h O R cefazolin, 1 g
every 8 h
Oral: dicloxacillin, 500 mg dour times daily O R cephalexin,
500 mg four times daily
IV: clindamycin, 600900 mg every 8 h, O R
15 mg/kg every 12 h
vancomycin,
therapy
generally
not
indicated
Treatment1
Penicillin
Allergic
Clinical
Findings
Treatment
The approach to treatment of ecthyma is the same
P.181
as for impetigo. Beyond removal of crusts and debris with warm
compresses, surgery is generally not indicated. Ecthyma caused
by P aeruginosa
and occasionally
therapy
CELLULITIS
Essentials
of
Diagnosis
General
Considerations
immunocompromised
Clinical
patients.
Findings
Differential
Diagnosis
Complications
Although many instances of limited cellulitis resolve without
treatment, cellulitis can cause serious disease by spreading
rapidly via lymph vessels and the bloodstream. Patients who
have undergone saphenous venectomy for myocardial
revascularization may develop recurrent acute cellulitis in the
involved limb, often
are generally caused
and commonly occur
serve as a nidus for
Treatment
Uncomplicated bacterial cellulitis is most commonly caused by hemolytic streptococci or S aureus. Because the clinical features
of streptococcal,
P.182
staphylococcal, or combined infections are usually similar, in
most cases therapy is directed against both streptococci and
staphylococci without confirmation of the etiology. If the
infection is mild, an oral agent such as dicloxacillin or a firstgeneration cephalosporin (eg, cephalexin) may be selected (see
Box 13-2 ). Either a semisynthetic penicillin (eg, nafcillin or
oxacillin) or a first-generation cephalosporin (eg, cefazolin)
would be an appropriate first-line parenteral agent for mild
cellulitis of undetermined etiology. Penicillin remains the drug of
choice for streptococcal cellulitis, such as with recurrent cellulitis
in a limb after saphenous venectomy.
Prognosis
The prognosis of most cases of simple bacterial cellulitis is good
with appropriate antimicrobial therapy. Scarring is generally not
encountered, and suppurative complications occur in a minority
of cases. Episodes of cellulitis may heal with the development of
lymphedema, thereby potentially predisposing the patient to
recurrent episodes in the same location.
Prevention
Treatment of tinea and management of edema in involved limbs
with appropriate mechanical measures such as support hose may
lessen the risk for the development of bacterial cellulitis.
CUTANEOUS
ABSCESSES
Essentials
Diagnosis
of
General
Considerations
Clinical
Findings
Complications
Complications of cutaneous abscesses include bacteremia and
spread of infection into adjacent structures, including bone or
joints.
Treatment
Most cutaneous abscesses require incision and drainage when
demonstrable fluctuance is present. If only a tender nodule is
encountered, needle aspiration may be performed, followed by
incision and drainage if pus is recovered. Because of the
potential for extension to the cavernous sinus, lesions on the
nose or lips should generally not be incised or otherwise
manipulated. If the lesion is effectively drained surgically,
antibiotic therapy may not be necessary. Antibiotic therapy is
generally reserved for high-risk patients with impaired host
defenses or for patients in whom there is evidence of
FURUNCLES
Clinical
AND
CARBUNCLES
Findings
nodules that
spreading to the
in moist areas
to friction (eg,
carriage
of S aureus.
Complications
Manipulation of furuncles on the upper lip or near the nasolabial
groove should be avoided, because it may result in cavernous
sinus thrombosis. Staphylococcal bacteremia may be encountered
with large, inflamed lesions, possibly resulting in metastatic
abscesses.
Treatment
For minor furuncles, moist heat should provide adequate therapy.
Topical or systemic anti-infective therapy is generally not
indicated. Larger furuncles and carbuncles require incision and
drainage as well as oral or, occasionally, parenteral
antistaphylococcal
therapy.
FOLLICULITIS
Clinical
Findings
Treatment
Anti-infective therapy is generally not indicated. Local heat may
provide symptomatic benefit.
NECROTIZING
INFECTIONS
Essentials
of
SOFT-TISSUE
Diagnosis
General
(eg,
GAS, Clostridium
Considerations
necrotizing
soft-tissue
infections
are
polymicrobial,
although
myonecrosis
Clostridium spp. (C
(gas
gangrene)
others)
Type-1
(polymicrobial)
Mixedaerobes
Type-2
necrotizing
and
fasciitis
anaerobes
(streptococcal)
necrotizing
fasciitis
S pyogenes
Progressive
bacterial
Microaerophilic
Proteus spp.)
Clostridial
C
synergistic
streptococci
anaerobic
gangrene
Plus S aureus (o r
occasionally
cellulitis
perfringens
Nonclostridial
anaerobic
cellutitis
Usual
Microbiology
CLOSTRIDIAL
GANGRENE)
General
MYONECROSIS
(GAS
Considerations
Clinical
Findings
septicum and is
Complications
Severe tissue destruction is generally encountered with gas
gangrene, which may lead to loss of limb or death.
Treatment
When Clostridium spp. have been demonstrated or are highly
suspected, high-dose penicillin G is generally considered the drug
of choice (see Box 13-4 ). Although some studies have shown
increasing resistance of clostridia to penicillin, almost all strains
Prognosis
Prompt recognition and adequate dbridement of devitalized
tissues are essential to minimize tissue loss. More proximal
amputation may sometimes be necessary if initial dbridement
is inadequate.
Prevention
Meticulous care of contaminated traumatic wounds, including
thorough dbridement of devitalized tissue and foreign
material, is essential to lessen the likelihood of the development
of gas gangrene.
Clostridial
anaerobic
cellulitis
(polymicrobial)
necrotizing
fasciitis
(streptococcal)
necrotizing
fasciitis
bacterial
synergistic
gangrene
myonecrosis
(gas
gangrene)
anaerobic
cellulitis
Treatment1
Penicillin
Allergic
NECROTIZING
General
FASCIITIS
Considerations
Clinical
Findings
Differential
Diagnosis
Complications
Complications of necrotizing fasciitis include compartment
syndromes, progressive limb necrosis leading to amputation,
Treatment
In all instances where drainage is present, aerobic and anaerobic
cultures and a Gram stain should be performed. Initial antiinfective therapy may then be based on the results of the Gram
stain morphology (see Box 13-4 ). When only streptococci are
seen on Gram stain in the setting of a necrotizing infectious
process, then high-dose penicillin G should be administered. It
has been suggested, from limited experimental data and
anecdotal clinical experience, that clindamycin should be
administered in addition to penicillin in cases of invasive infection
caused by S pyogenes , because of the theoretical ability of
clindamycin to interfere with streptococcal toxin production.
There is also anecdotal evidence supporting the use of
intravenous gammaglobulin in cases of streptococcal necrotizing
fasciitis. No controlled data are available to clearly define the
potential additive benefit of this costly adjunctive therapeutic
modality, however.
When the Gram stain reveals several bacterial morphologies,
broad-spectrum antibacterial therapy should be directed at grampositive and gram-negative anaerobic and aerobic/facultative
organisms. Polymicrobial Gram stain findings may be
encountered in many of the polymicrobial syndromes described
above, including type-1 necrotizing fasciitis, progressive
synergistic gangrene, and nonclostridial anaerobic cellulitis.
Reasonable initial therapeutic regimens, pending definitive
culture and susceptibility data, include (1) a third-generation
cephalosporin (eg, cefotaxime or ceftriaxone) in combination with
metronidazole or clindamycin; (2) ampicillin, gentamicin, and
clindamycin or metronidazole; (3) piperacillin/tazobactam
monotherapy; or (4) imipenem monotherapy.
Prognosis
The prognosis of necrotizing fasciitis largely depends on early
recognition, prompt institution of antimicrobial therapy, and early
PROGRESSIVE
SYNERGISTIC
BACTERIAL
GANGRENE
ANAEROBIC
CELLULITIS
of
Diagnosis
or
bone.
General
Considerations
corrodens
Cat Bites. Cats have slender and extremely sharp teeth that
typically cause a puncture-type injury with potential
involvement of bone or joint. The overall rate of wound
infection after cat bites is >50%, with a proportionate
increase in the incidence of associated septic arthritis and
osteomyelitis. P multocida is the most frequently isolated
pathogen, occurring in >50% of cases. Other organisms,
similar to those associated with dog bite injuries, may also
be
recovered.
Dog
Streptococci, S aureus, Eikenella corrodens, Pasteurella
multocida, Capnocytophaga canimorsus , anaerobes
Cat
P multocida , streptococci, anaerobes
Human
S aureus, E corrodens, H influenzae , anaerobes
Type of Bite
Usual
Microbiology
Treatment
Wounds should be irrigated with saline and may require
dbridement and surgical repair depending on the severity of
the injury. The risk for rabies infection should be assessed
carefully and appropriate prophylaxis given, if indicated. Tetanus
prophylaxis should also be addressed. If a wound is brought to
clinical attention >24 h after injury or if there are already signs
of infection, it should be left open. If a patient presents with an
infected wound, cultures for aerobic and anaerobic bacteria
should be obtained. Radiography should be pursued if an
underlying fracture is suspected. In general, relatively trivial bite
wounds may not require antibiotic therapy, although it may be
prudent to administer a short (3- to 5-day) course of a
prophylactic oral antibiotic (eg, amoxicillin/ clavulanate) in the
setting of a more significant bite injury (especially for cat bite
injuries) (Box 13-6 ). For an infected wound requiring
hospitalization, ampicillin/sulbactam would be a reasonable initial
empiric
therapeutic
choice.
DIABETIC
FOOT
Essentials
of
INFECTIONS
Diagnosis
usually
caused
by S
Dog
Oral: amoxicillin/clavulanate, 500 mg three times daily
Parenteral: ampicillin/sulbactam, 3 g every 6 h
Oral: Levofloxacin 500 mg once daily O R gatifloxacin 400 mg
once daily
PLUS
Clindamycin 300 mg every 6 h O R metronidazole 500 mg
every 6 h
Parenteral: levofloxacin 500 mg IV once daily O R gatifloxacin
400 mg IV once daily
PLUS
Clindamycin 900 mg IV every 8 h O R metronidazole 500 mg
IV every 6 h
Cat
Oral: amoxicillin/clavulanate, 500 mg three times daily
Parenteral: ampicillin/sulbactam, 3 g every 6 h
Human
Oral: amoxicillin/clavulanate, 500 mg three times daily
Parenteral: ampicillin/sulbactam, 3 g every 6 h
1
Treatment1
Penicillin
Allergic2
General
Considerations
NonLimb-Threatening
Infections. Mild
Mild
nonlimb-threatening
infections
limb-threatening
infections
Usual
Microbiology
Clinical
Findings
Complications
Complications of diabetic foot infections include persistence of
infection, osteomyelitis, septic arthritis, progressive infection
necessitating amputation, and systemic infection with severe
toxicity.
Treatment
Selection of antimicrobial therapy (Box 13-8 ) depends to a large
extent on the nature and severity of infection. In cases of mild
nonlimb-threatening cellulitis without evidence of tissue
necrosis and in the absence of a foul odor, therapy may be
directed at gram-positive cocci (ie, S aureus ) with a firstgeneration cephalosporin such as cefazolin. In select cases, oral
therapy with an agent such as dicloxacillin or cephalexin may be
appropriate. More severe infections, particularly those with
associated tissue necrosis, generally require broader-spectrum
therapy. Possibilities include piperacillin/tazobactam, imipenem
or meropenem, or combination therapy such as cefepime with
clindamycin or metronidazole. Therapy should be guided by
culture and susceptibility data if appropriate specimens are
available for culture. Duration of antimicrobial therapy depends
on specific clinical circumstances. Cases of mild cellulitis are
Prognosis
The outcome of the treatment of diabetic foot infections is to a
great extent related to the underlying vascular and neurologic
status of the limb. In infections involving relatively well-perfused
limbs, amputation is less likely to be necessary for ultimate cure.
In general, severe infection in severely ischemic limbs requires
amputation.
Mild
non-limb-threatening
infections
1.53 g IV every 6 h
Oral: clindamycin, 300 mg four times daily
Parenteral: clindamycin, 600900 mg every 8 h, O R
vancomycin, 15 mg/kg every 12 h
Severe
limb-threatening
infections
Treatment1
Penicillin
Allergic
Prevention
Preventive measures that may lessen the incidence of diabetic
foot infections include meticulous foot care, the use of properly
fitting footwear, early treatment of mild infections, and
optimizing blood flow to ischemic feet through revascularization
procedures, if possible.
REFERENCES
Bisno AL, Stevens DL: Streptococcal infections of skin and
1992;6:693.
2001
McGraw-Hill
Infectious
Arthritis
&
Prosthetic-Joint
Infection
14
Osteomyelitis,
Infectious
Arthritis & Prosthetic-Joint
Infection
Douglas R. Osmon MD
James M. Steckelberg MD
OSTEOMYELITIS
Essentials
of
Diagnosis
osteomyelitis
but
are
expensive.
General
Considerations
Stage
Stage
Stage
1:
2:
3:
medullary osteomyelitis
superficial osteomyelitis
localized osteomyelitis
and
local
vascularity
Diabetes
mellitus
Chronic
hypoxia
Immune
disease
Malignancy
Extremes of age
Immunosuppression
Local (Bi)
Chronic
lymphedema
Major vessel compromise
Small vessel disease
Vasculitis
Venous stasis
Extensive
scarring
Radiation
fibrosis
Neuropathy
Tobacco abuse
1 Source: Mader et al 1996.
Table
Staphylococcus
aureus
Most frequent cause of all types of ostemyelitis
Coagulase-negative
staphylococci
Common if orthopedic fixation devices are present
Streptococci
Diabetes mellitus, bite injuries
Enterobacteriaceae
Nosocomial infection or contaminated open fractures
Pseudomonas
aeruginosa
Injection drug users and osteomyelitis of the foot after puncture
injuries
Anaerobic bacteria
Osteomyelitis of the foot in patients with diabetes mellitus or
after human and animal bites
Salmonella spp. or Streptococcus
pneumoniae , S aureus
Sickle cell disease
Pasteurella
multocida or Eikenella
corrodens
Bite injuries
1 Adapted from Lew & Waldvogel 1997.
Microorganisms
Common
Clinical
Association
Clinical
Findings
Hematogenous
osteomyelitis.
osteomyelitis.
osteomyelitis.
Laboratory
findings. The leukocyte and the
erythrocyte sedimentation rates are often normal. Blood
cultures are usually negative. A bone biopsy is
diagnostic and is usually obtained at the time of surgical
dbridement.
Imaging. Because the time from onset of infection to
diagnosis of osteomyelitis is often delayed with
contiguous focus osteomyelitis, plain radiographs,
including tomography, often show abnormalities
consistent with osteomyelitis. In the proper clinical
setting, such as the presence of a draining sinus tract,
plain radiography may be all that is required. In some
circumstances, however, there are other pathologic
processes present that mimic osteomyelitis (ie,
neuropathic bone disease in patients with peripheral
neuropathy), or there are partially healed fractures or
orthopedic fixation devices in place that limit the
usefulness of plain radiography. If the clinical situation
warrants additional radiologic procedures to confirm the
diagnosis of osteomyelitis or to help identify the optimal
surgical therapy for the patient, MRI is the diagnostic
test of choice. If orthopedic hardware is present that
interferes with MRI examination, then the combination
of a three-phase (99 Tc) technetium bone scan and
indium-labeled leukocyte scan can be performed.
P.195
Differential
Diagnosis
Complications
Failure of medical and surgical therapy of osteomyelitis
invariably leads to a relapse of infection. If treatment is
delayed, osteomyelitis can progress from superficial to diffuse
disease or from Cierney/ Mader stage 1 or 2 to stage 3 or 4 and
thus become much more difficult to eradicate. In severe cases,
amputation may be required for control of infection. In addition,
acute hematogenous osteomyelitis in children can spread to
adjacent joints and cause infectious arthritis. Vertebral
osteomyelitis in adults if untreated can cause neurologic
sequelae including paralysis either through extension to the
epidural space or spinal column instability. Rare complications
of longstanding osteomyelitis include amyloidosis, squamous cell
carcinoma at the site of chronic sinus tract or primary bone
malignancies such as osteogenic sarcoma.
Treatment
The treatment of osteomyelitis depends on the goals of therapy
and requires a multidisciplinary team of physicians, which may
include the orthopedist, neurosurgeon, oral surgeon, plastic
surgeon, vascular surgeon, invasive radiologist, and infectious
disease specialist. If eradication of infection is the goal, then, in
most circumstances, extensive dbridement and resection of
dead and infected bone are required, in conjunction with
appropriate dead-space and soft-tissue management, rigid
fixation of fractures, local antimicrobial therapy with antibioticimpregnated polymethylmethacrylate beads, and prolonged
systemic antimicrobial therapy directed at the causative
organisms. In addition, modification of any physiologic factors
osteomyelitis suggest that the addition of rifampin to betalactams or vancomycin for osteomyelitis caused by S aureus
may be beneficial, but confirmation in clinical trials is needed
before this practice can be routinely recommended.
The choice of a specific antibiotic depends on the antimicrobial
activity, pharmacokinetics, tissue penetration, and potential
toxicities of the antimicrobial
Integration of this knowledge
allergies, current medications,
hepatic and renal insufficiency
and
hypersensitivity
to
penicillin)
Antibiotic
Therapy1
Alternative
Therapy1
Prognosis
Despite state-of-the-art medical and surgical therapy for
osteomyelitis, relapse of infection occurs. Relapse is more
common in cases of chronic osteomyelitis than acute
osteomyelitis and can occur in 2530% of cases. Relapse
of infection is most often caused by suboptimal surgical
dbridement rather than a failure of antimicrobial therapy.
Therefore, it is probably best not to think in terms of a cure for
osteomyelitis but prolonged arrest of the disease process.
Prevention
Specific strategies to prevent osteomyelitis depend on the type
of osteomyelitis. Decreasing the incidence of infections that
predispose to transient or sustained bacteremia will prevent
hematogenous osteomyelitis. Therefore, efforts to reduce the
incidence of community- and nosocomially acquired infections
such as pneumonia, urinary tract infections and soft-tissue
infections through vaccination, infection control measures, and
early treatment of established infection will prevent
hematogenous osteomyelitis. The incidence of contiguous-focus
osteomyelitis can be reduced through efforts such as improved
foot care in patients with diabetes mellitus and infection control
efforts to reduce the incidence of surgical-site infections after
orthopedic and neurosurgical procedures.
INFECTIOUS
ARTHRITIS
Essentials
Diagnosis
of
leukocyte
General
Considerations
Infectious arthritis is
14-2 ). It is usually
joint. Synovial tissue
basement membrane
Figure
S aureus
66
Streptococci3
20
H influenzae
1
Aerobic gram-negative bacilli
10
Polymicrobial and miscellaneous
1
Unknown
Percentage
group
Clinical
Findings
Differential
Diagnosis
Treatment
The principles in the management of infectious arthritis include
drainage of the purulent synovial fluid, dbridement of any
concomitant periarticular osteomyelitis, and the administration
of appropriate parenteral antimicrobial therapy. Experimental
models of infectious arthritis suggest that early drainage and
antimicrobial therapy prevent cartilage destruction. Local
antimicrobial as opposed to systemic therapy is unnecessary.
Joint immobilization and elevation are useful for symptomatic
relief of pain early in the course of the disease, but early active
range-of-motion therapy is beneficial for ultimate functional
outcome.
The optimal method of drainage of an infected joint remains
controversial, in part because no well-controlled randomized
trials exist to guide therapy. Most children, except patients with
infectious arthritis of the hip, and patients with gonococcal
infection do not require repeated joint aspirations or
arthrotomy. Historically, most adults with infectious arthritis
have been managed with repeated joint aspirations, not surgical
dbridement. Arthrotomy has been reserved for cases in
which there is failure to improve within 7 d of conservative
therapy, inability to adequately drain the infected joint by
aspiration either due to location (hip and shoulder) or
loculations of purulence within the joint, and longstanding
infectious arthritis. The exact role of arthroscopy remains
unknown but is an attractive option for the initial therapy of
infectious arthritis because of the minimal morbidity of the
procedure and its improved ability to adequately drain purulent
material from the joint compared with joint aspiration.
Randomized trials are urgently needed to evaluate all of these
modalities.
Prognosis
Patients with infectious arthritis have an estimated case fatality
rate of 9%, but, in patients with polyarticular infectious arthritis
and rheumatoid arthritis, it is 56%. Of patients who
survive, 42% will have a permanent loss of joint function.
Predictors of morbidity and mortality include older age, the
presence of rheumatoid arthritis, infection in the hip or
shoulder, >1-wk duration of symptoms before treatment,
involvement of more than four joints, persistently positive
cultures after 7 d of appropriate therapy, and the presence of
bacteremia.
Prevention
PROSTHETIC-JOINT
Essentials
of
INFECTION
Diagnosis
prosthesis
implantation.
symptoms.
General
Considerations
prosthetic-joint
infections
occur
in
immunocompetent
Coagulase-negative
staphylococci
254 (25)
S aureus
240 (23)
Polymicrobial
147 (14)
Gram-negative
bacilli
114 (11)
Streptococci1
79 (8)
Unknown2
83 (8)
Anaerobes
62 (6)
Enterococci
29 (3)
Other
microorganisms
25 (2)
Total
1033 (100)
1 Includes beta-hemolytic streptococci and viridans group
streptococci.
2 Includes cases in which there was no growth on routine
bacterial cultures, routine bacterial cultures were not obtained,
or microbiologic information was not available.
Microorganisms
Clinical
Findings
sufficient to definitively make the diagnosis of prostheticjoint infection. Multiple positive cultures from either a
preoperative joint aspiration or an intraoperatively obtained
tissue are diagnostic for prosthetic-joint infection. Blood
cultures should be obtained if fever is present. In addition
the presence of acute inflammation on a frozen section of
periprosthetic tissue is an accurate way to identify infection
intraoperatively at the time of revision surgery prior to the
culture results. Because of the importance of making a
microbiologic diagnosis antimicrobial therapy should usually
be withheld until all aspirates have been obtained and/or
the surgeon has obtained intraoperative cultures from the
joint. If antimicrobial therapy has already been started,
when possible it should be stopped for 10-14 d before any
diagnostic procedure to avoid false-negative culture results.
As much fluid for culture as possible should be obtained at
the time of diagnostic joint aspiration.
Imaging. Plain radiographs, arthrograms, and radionuclide
imaging are often useful in diagnosing prosthetic-joint
infection (Figure 14-3 ). Abnormalities that can be seen on
plain radiography include loosening of the prosthesis,
lucency at the bone-cement interface, and periostitis or
other evidence of osteomyelitis. An arthrogram can confirm
the presence of a loose prosthesis and often allows for
simultaneous aspiration of the joint for culture. The
combination of a three-phase 99 Tc bone scan and an
indium-labeled leukocyte scan is the most sensitive
P.201
and specific radionuclide test for the presence of prostheticjoint infection.
Differential
Diagnosis
Complications
Failure of diagnosis and treatment of prosthetic joint infection
may lead to chronic pain, loosening and failure of the
prosthesis, loss of limb function, and rarely amputation.
Squamous cell carcinoma may rarely complicate a draining sinus
tract.
Treatment
&
Prognosis
Prevention
Perioperative
Infection. The preponderance of evidence in
multiple clinical trials favors the use of antimicrobial
prophylaxis at the time of joint placement compared with no
prophylaxis. Prophylactic antimicrobial agents should be
directed against the common organisms that cause
postoperative wound infection. Because staphylococci and
streptococci are the most common organisms to cause these
infections, agents directed against these pathogens, such as
penicillinase-resistant penicillins and first-generation
cephalosporins, are often used. Recent studies also suggest
that antibiotic-impregnated cement may be effective in the
prophylaxis of deep wound infection after total joint
replacement. Further studies with longer follow-up periods
are needed before this practice can be endorsed. The utility
of laminar airflow devices in preventing prosthetic-joint
infection
remains
controversial.
Hematogenous
Infection. The majority of hematogenous
infections are caused by S aureus , coagulase-negative
staphylococci, and beta-hemolytic streptococci, presumably
from a skin source. Urinary tract and respiratory tract
infections have also been
P.202
implicated as sources of infection. It seems prudent to
aggressively diagnose and treat systemic infections in
patients with a prosthetic joint, to prevent hematogenous
seeding of the prosthesis. Optimal antimicrobial therapy for
these infections will depend on the source of infection, in
vitro susceptibility of the organism causing infection, and
the patient's history of antibiotic allergies.
Antimicrobial prophylaxis is controversial for patients with a
prosthetic joint who undergo a dental procedure or invasive
procedures such as endoscopy and cystoscopy. Guidelines
for this practice have recently been published.
REFERENCES
Carragee EJ: Pyogenic vertebral osteomyelitis. J Bone J Surg
1997;79:874. (Most recent review from surgical
perspective.)
Fitzgerald RH et al: Advisory statement: antibiotic
prophylaxis for dental patients with total joint replacements.
American Dental AssociationAmerican Academy of
Orthopedic Surgeons. J Am Dent Assoc 1997;128:1004.
Haas DW, McAndrew MP: Bacterial osteomyelitis in adults:
evolving considerations in diagnosis and treatment. Am J
Med 1996;101:550. (Excellent review of antimicrobial
therapy.)
Lew DP, Waldvogel FA: Osteomyelitis. N Engl J Med
1997;336:999.
(Most
recent
review.)
(Review
from
surgical
perspective.)
1995;20:225.(Excellent
review.)
2001
McGraw-Hill
Transmitted
Diseases
15
Sexually
Transmitted
Diseases
John W. Wilson MD
Nancy K. Henry PhD, MD
URETHRITIS
Essentials
of
Diagnosis
General
Considerations
The Centers for Disease Control and Prevention estimates that NGU is 2.5-fo
more prevalent than gonococcal urethritis in the United States and much of
Etiology
Box 15-1 lists causative organisms associated with various forms of urethrit
Noninfectious causes exist but should be considered only after infectious
pathogens are excluded.
Gonococcal
Urethritis. N gonorrhoeae is a gram-negative intracellular
coccus that characteristically grows in pairs (diplococci). Two points
deserve special mention. First, over the last 25 years, the prevalence of
penicillin- and tetracycline-resistant gonococci has been increasing
worldwide, requiring alternative treatment strategies. Second, N
gonorrhoeae may not be limited to urethritis. Patients may present with
coinfection of the cervix, rectum, or pharynx or have symptoms of
disseminated
infection.
Nongonococcal
Urethritis. C trachomatis is the most common pathoge
of NGU. It is isolated in 3050% of patients with NGU. U urealyticum i
found in 2025% of cases. The other infectious causes of NGU account
for 15% of cases and include Trichomonas
vaginalis , herpes simplex
virus (HSV), Mycoplasma
genitalium , and Candida spp. The causes for t
remaining 2030% of NGU cases remain unclear.
of men with NGU compared with those without NGU. Men with NGU and U
urealyticum isolated from the urethra respond better to antimicrobial
agents with antiureaplasma activity than to those without antiureaplasm
activity.
NGU
to
metronidazole
has
been
demonstrated.
Infectious
Gonococcal
Neisseria
gonorrhoeae
Nongonococcal
Chlamydia
trachomatis
Ureaplasma
urealyticum
Trichomonas
vaginalis
Herpes simplex virus
Mycoplasma
genitalium
Candida spp.
Noninfectious
Organism/Cause
Clinical
Findings
Signs and Symptoms. See Table 15-1 for a comparison of the clinical
findings associated with gonococcal urethritis and NGU. Distinguishing
between them may be difficult. The incubation period for gonococcal
Findings.
P.205
antigens within the urethra, cervix, and urine. The Gen-Probe Pace 2 use
nonisotopic probes to detect ribosomal RNA. LCR utilizes a DNA
amplification technique to detect trace amounts of organism-specific
nucleic acid sequences from urethral and endocervical swab specimens a
urine samples.
Onset of symptoms
Classically abrupt
75% men develop symptoms within 4 days; 8090% men develop
symptoms within 2 weeks
Less acute onset
Approximately 50% men develop symptoms within 4 days
Frankly purulent
75%
1133%
urethral
discharge
Mucopurulent
discharge
25%
50%
Completely clear discharge
4%
1050%
Dysuria
7388%
5375%
Clinical
Finding
Table
Gonorrhea
NGU
Differential
Diagnosis
Complications
Treatment
Gonococcal
identified and found to have acquired plasmids encoding for the product
of beta-lactamase. Approximately 15% of all gonococci in the United
States are now penicillin resistant. In some urban areas, the incidence is
P.206
of the aforementioned cephalosporins and quinolones, but the organisms
responsible for NGU are often spared. PGU should be suspected if signs,
symptoms, or laboratory evidence of urethritis is found 47 days after
single-dose treatment for gonococcal urethritis. Unless chlamydial infect
has been specifically ruled out through testing, all patients treated for
gonococcal infections should also be treated for chlamydial infection.
Nongonococcal
Urethritis. Empiric therapy is directed against the two
most common pathogens, C trachomatis and U urealyticum. Oral
doxycycline has been the traditional drug of choice for NGU. It is highly
effective against C trachomatis and moderately effective against U
urealyticum , and it is inexpensive. Azithromycin is a first-line drug that
can be administered as a single oral dose. This offers a significant
advantage of increased patient compliance, but is more expensive than
doxycycline. For acute nongonococcal urethritis in men, single-dose oral
Empiric
Gonococcal
urethritis (N
gonorrhoeae )
Ceftriaxone, 125 mg IM 1
Ciprofloxacin, 500 mg orally 11
Ofloxacin, 400 mg orally 1
Cefixime, 400 mg orally 1
Spectinomycin, 2 g IM 12
Ceftizoxime, 250500 mg IM 1 3
Cefuroxime axetil, 1 g orally 13
Nongonococcal
urethritis (C
trachomatis or U
urealyticum )
Urethritis
Retreat
Metronidazole, 2 g orally 15 plus erythromycin base, 500 mg orally fo
times daily 7 d
OR
Erythromycin ethylsuccinate, 800 mg orally four times daily 7 d
1
Spectinomycin, once widely used for the treatment of gonorrhea, has the
disadvantages of higher cost, requirement for injection, and lack of sustaine
high-serum bactericidal levels.
3 Ceftizoxime and cefuroxime are well tolerated but less active.
4 Doxycycline should not be used during pregnancy.
5 Metronidazole should not be given during the first trimester of pregnancy.
Metronidazole may cause a disulfiramlike reaction with alcohol.
Syndrome/Microorganism
First-Line
Therapy
Alternative
Therapy
Prognosis
should also be avoided until infected partners have been adequately treated
CERVICITIS
Essentials
of
Characterized
by
Diagnosis
purulent
or
mucopurulent
endocervical
discharge.
presents
without
symptoms.
General
Considerations
Cervicitis is the most common STD syndrome in women and is caused prima
by N gonorrhoeae, C trachomatis , HSV, and human papillomavirus (HPV). It
represents an inflammation of the columnar and subepithelium of the
endocervix and can involve any contiguous columnar epithelium that lies
exposed on the ectocervix. In adolescent girls, the transition zone is
frequently everted over part of the ectocervix, thereby increasing the amoun
of susceptible columnar tissue exposed to a pathogen. This biological
circumstance, combined with an increased number of sexual partners withou
barrier methods of contraception, places adolescent girls at highest risk for
cervicitis from an STD pathogen. Interestingly, oral contraceptives cause
cervical eversion (ectropion) and may increase the risk of chlamydial infecti
but have not been shown to increase gonococcal infection.
Even though most of these organisms also cause male urethritis, there is a
strong gender bias for infection in women. Male-to-female transmission of
infection is more common than female to male.
Clinical
Findings
Laboratory
Findings. The presence of cervicitis can be established by a
variety of diagnostic procedures, including Gram stain of the endocervic
mucus, cervical cytology, colposcopy, and cervical biopsy. The microscop
presence of 10 leukocytes per high-power field supports the diagnosis of
mucopurulent cervicitis. Gram-negative intracellular diplococci on a stain
staining. Viral isolation will permit the differentiation of HSV-1 from HSV
This has prognostic significance because HSV-1 is less likely than HSV-2
cause recurrent genital herpes.
Differential
Diagnosis
Symptoms of dysuria, vaginal discharge, and abdominal pain are not specific
for cervicitis. Vulvovaginitis, pelvic inflammatory disease (PID), urethritis,
P.208
and cystitis may produce a similar clinical picture. A speculum exam and
urinalysis are indicated to rule out vaginitis, urethritis, and cystitis. Erythem
around the cervical os can indicate infection or merely represent cervical
ectropion.
Complications
Gonococcal and chlamydial infections are the most common causes of PID,
ectopic pregnancy, and impaired fertility in women. If not adequately treate
Treatment
The treatment options for gonococcal and chlamydial cervicitis are the same
those described for infectious urethritis (Box 15-2 ). The treatment program
should always include activity against both C trachomatis and N gonorrhoeae
The tetracyclines, including doxycycline, and the quinolones are
contraindicated during pregnancy. For pregnant patients, erythromycin (base
or ethylsuccinate) or amoxicillin is recommended for anti-Chlamydia therapy
Treatments for HSV and HPV are described later.
Prognosis
VULVOVAGINITIS
Essentials
of
Diagnosis
enables
identification
of Candida
General
Considerations
The three most common types of vaginal infections in adult women are
vulvovaginal candidiasis (2025%), BV (3045%), and trichomoniasis
(1520%). Other less common pathogen-related causes include ulcerative
vaginitis attributed to Staphylococcus
aureus toxins in women with toxic sho
syndrome, clindamycin-responsive desquamative inflammatory vaginitis, gro
A streptococcal vaginitis, and idiopathic vulvovaginal ulceration associated w
HIV infection.
Vulvovaginal
Candidiasis. An estimated 75% of women experience at
least one episode of vulvovaginal candidiasis during their lifetime, and
4050% will have two or more episodes. Recurrent vulvovaginal
candidiasis is defined as four or more episodes of infection per year and
occurs in < 5% of healthy women. The role of vulvovaginal candidiasis a
an STD is controversial. Candida spp. are among the normal vaginal flor
and vulvovaginal candidiasis
P.209
can occur in women who have never engaged in sexual activity. Nonsexu
predisposing risk factors for the development of vulvovaginal candidiasis
include the use of broad-spectrum antibacterial agents, oral
Bacterial
Vaginosis. BV is the most common cause of infectious vagini
It signifies a change in the normal vaginal flora characterized by the
replacement of hydrogen peroxide-producing lactobacilli with high
concentrations of anaerobic bacteria (eg, Bacteroides spp., Mobiluncus
Clinical
Findings
Table 15-3 summarizes the clinical and microscopic findings associated with
vaginitis.
Vulvovaginal
Bacterial
Vaginosis. Affected women usually complain of a slightly
increased malodorous vaginal discharge that is gray-white in color, thin,
and homogenous. Pruritus and vulvar inflammation are notably absent.
Many women with BV are asymptomatic.
The pH of the vaginal fluid is elevated above 4.5 (usually in the range of
Gram stain of the vaginal fluid shows vaginal epithelial cells covered wit
coccobacilli. These characteristic epithelial cells are called clue
cells. Established diagnostic criteria for BV require three of the
following four signs: (1) presence of clue cells, (2) homogenous
noninflammatory discharge adherent to vaginal walls, (3) vaginal fluid p
>4.5, and (4) positive whiff test.
Symptoms
None
Pruritus
Soreness
Dyspareunia
Soreness
Dyspareunia
Often asymptomatic
Often asymptomatic
Occasional abdominal
Discharge
Amount
Variable
pain
Scant/moderate
Profuse
Moderate
Color
Clear/white
White
Green-yellow
White/gray
Consistency
Nonhomogenous
floccular
Clumped, adherent
Homogenous, frothy
Homogenous
adherent
Vaginal fluid pH
4.04.5
4.04.5
5.06.0
>4.5
Amine test (fish odor)
None
None
Usually positive
Positive
Microscopy
Saline
PMN:EC ratio<1 Lactobacilli predominate
PMN:EC <1
Pseudohyphae
(~40%)
PMN:EC >1
Motile trichomonads PMNs predominate
Normal
Table
Vulvovaginal
Candidiasis
Trichomoniasis
Bacterial
Vaginosis
Vulvovaginal
Intravaginal
Candidiasis
agents 1 :
for 7 days2
Nystatin, 100,000 U vaginal tablet, one tablet for 714 days
Tioconazole, 6.5% ointment 5 g in a single application2 ,3
agents:
agents
Vaginosis
Syndrome/Microorganism
First
Choice
Alternative
Choice
Differential
Diagnosis
Toxic shock syndrome with S aureus can produce vaginitis along with
characteristic symptoms of fever, rash, hypotension, multiorgan abnormaliti
Complications
Treatment
Vulvovaginal
Candidiasis. Vulvovaginal candidiasis can be successfully
treated with topical antifungal agents in >80% of cases (Box 15-3 ). The
are a variety of topical agents, including butoconazole, clotrimazole,
miconazole, nystatin, tioconazole, and terconazole. They are applied
Prognosis
GENITAL
Essentials
ULCER
of
DISEASE
Diagnosis
General
Considerations
Genital ulcer disease involves a disruption of the skin and mucous membran
of the genitalia and often is the presenting complaint of a sexually acquired
infection. Treponema pallidum is the spirochete responsible for all stages of
syphilis. It is the second most common cause of genital ulcer disease in both
underdeveloped and developed countries, although it is more common in the
latter. Haemophilus
ducreyi , a gram-negative bacillus, is the organism
responsible for chancroid. The disease is most prevalent in Africa and
Clinical
Findings
Table 15-4 summarizes the clinical findings associated with genital ulcer
disease.
Signs and Symptoms.
Primary
and shaft of the penis are common sites. Homosexual men may manifest
herpetic lesions over the perianal area. Several days after the appearan
of the vesicles, they rupture, creating shallow, intensely painful ulcers t
subsequently become crusted. Urethritis may occasionally develop.
27 d
Avg. 1014d
Range 3 d3 wk
Variable
Number of lesions
Usually single, occasionally
13; may be multiple
multiple
Syphilis
Table
Chancroid
Genital
Lymphogranuloma
Herpes
Venereum
Donovanos
Lymphogranuloma
LGV. The first stage is marked by the formation of a primary genital skin
or mucosal lesion in the form of a papule or herpetiform ulcer. It usually
develops between 3 days and 3 weeks (up to 6 months) after exposure.
is painless and transient, and it heals rapidly without scarring. It is often
absent
in
Laboratory
donovanosis.
Findings.
P.214
media containing supplemented agar and vancomycin in a CO2 -enriched
Lymphogranuloma
Venereum. The isolation of C trachomatis from an
inguinal lymph node aspirate is the most definitive test for the diagnosis
LGV. However, the recovery of Chlamydia spp. by this method is < 30%.
Serologic testing is an alternative diagnostic method.
Donovanosis. The diagnosis of donovanosis is usually made clinically
based on the history and exam findings on a patient with recent sexual
Differential
Diagnosis
Complications
All genital ulcers are prone to secondary bacterial infections with a variety o
genital bacteria. Additionally, edema of the foreskin in uncircumcised men m
produce phimosis. Without treatment, chancres of primary syphilis and lesio
of genital herpes heal spontaneously. Patients with syphilis progress into the
secondary stage, whereas those with genital herpes may later experience
recurrence of their lesions. The ulcers of chancroid and LGV continue to grow
slowly by local extension and can produce further tissue and organ damage.
LGV may further lead to perianal abscesses and rectovaginal, rectovesical, a
anal fistulas and strictures. Lymphatic obstruction and edema may occur.
Rectal LGV is associated with an increased incidence of rectal cancer.
Complications of donovanosis scarring include urethral, vaginal, and anal
strictures and lymphedema of the external genitalia.
Treatment
Primary Syphilis. Penicillin remains the treatment of choice for any stage o
syphilis (Box 15-4 ). For early syphilis (primary, secondary, and latent syph
of < 1 year's duration), a single intramuscular dose of benzathine penicillin
OTHER
SEXUALLY
TRANSMITTED
DISEASES
HUMAN
PAPILLOMAVIRUS
There are >70 different HPV genotypes based on differences within the DNA
structure. HPV types 6 and 11 cause condyloma acuminatum (anogenital
warts), the most common viral STD in the United States, which is rarely
associated with cervical dysplasia. HPV types 16, 18, 31, 33, and 35 cause
cervical infection, which is present in ~20% of reproductive-age women in t
United States. Cervical infection is the most common source of squamous ce
abnormalities on Pap smears and has a direct oncogenic association with
cervical cancer.
2.
MOLLUSCUM
CONTAGIOSUM
PELVIC
INFLAMMATORY
DISEASE
exam there may be cervical motion and adnexal and lower abdominal
tenderness. It is important to diagnose and treat PID as early as possible. F
patients requiring hospitalization, intravenous cefoxitin or cefotetan plus
doxycycline (IV or oral) can be given (Box 15-5 ). Alternatively, intravenous
EPIDIDYMITIS
In men under age 35, the most common pathogens are N gonorrhoeae and C
trachomatis. Homosexual men may have enteric pathogens from rectal
intercourse. Unilateral testicular pain and tenderness are common. There is
usually palpable swelling of the epididymis. The evaluation and diagnostic te
are the same as those for urethritis. Treatment regimens include ceftriaxone
plus doxycycline or ofloxacin (Box 15-5 ).
PROCTITIS
P.218
(including LGV serovars), T pallidum (syphilis), and HSV. Treatment includes
ceftriaxone plus doxycycline (Box 15-5 ).
Primary
Syphilis
Recurrent
Suppressive
disease
therapy
HIV/immunosuppressed
patients
Acyclovir, 200 mg orally five times daily or 400 mg orally three times da
for 10 days4
disease
Lymphogranuloma
Venereum
Donovanosis
500
1 g
500
750
500
First
Choice
Choice
Pelvic Inflammatory
Parenteral Regimen1
Disease
Regimen2
First
Choice
Alternate
Choice
Prevention
first sexual encounter and first STD, number of previous STDs, number of
partners, risk assessment of those partners, type of contraception used (if
any), and future plans for sexual activity. Once the risk factors are identified
the educational process can begin.
the potential for STD transmission. Male condoms, when used correctly, are
the most effective method in preventing infections transmitted between
mucosal surfaces and transmission of HIV disease. Condoms do not cover all
exposed skin areas and may be less effective in preventing infections
P.219
Not only will early diagnosis and treatment prevent the serious, long-term
complications of STDs, but it will also help reduce the spread of disease with
a community.
As stated earlier, all patients with an STD should be evaluated for other STD
The presence of one pathogen doesn't eliminate the possibility of other
coinfecting pathogens or an earlier untreated infection with a different
pathogen. The physician must balance a high index of suspicion with screeni
programs to diagnose STDs as early as possible and to break the chain of ST
transmission.
REFERENCES
Urethritis
Kreiger JN: Trichomoniasis in men: old issues and new data. Sex Transmit
Dis 1995;22:83.
Lind I: Antimicrobial resistance in Neisseria
1997;24(Suppl
1):S93.
trachomatis genital
Cervicitis
Centers for Disease Control and Prevention: 1998 guidelines for treatment
of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:49.
Majeroni BA: Chlamydial cervicitis: complications and new treatment
options. Am Fam Physician 1994;49: 1825.
Miller KE: Women's health: sexually transmitted diseases. Prim Care Clin
Off Pract 1997;24:179. (Women's health. Sexually transmitted diseases.)
Zenilman JM: Gonorrhea: clinical and public health issues. Hosp Pract
1993:29.(Review.)
Vulvovaginitis
Centers for Disease Control and Prevention: 1998 Guidelines for treatment
of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:70.
Holmes KK: Lower genital tract infections in women. In Holmes KK et al:
Sexually Transmitted Diseases , 3rd ed. McGraw-Hill, 1999.
Genital
Ulcer
Disease
Centers for Disease Control and Prevention: 1998 Guidelines for treatment
of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:18.
Mroczkowski TF, Martin DH: Genital ulcer disease. Dermatol Clin.
1994;12:753.
Ballard RC: Genital ulcer adenopathy syndrome. In Holmes KK et al:
Sexually Transmitted Diseases , 3rd ed. McGraw-Hill, 1999.
Schulte JM, Schmid GP: Recommendations for treatment of chancroid,
1993. Clin Infect Dis 1995;20 (Suppl 1):S39.
Other
Sexually
Transmitted
Diseases
Centers for Disease Control and Prevention: 1998 Guidelines for treatment
of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47.
Prevention
Centers for Disease Control and Prevention: 1998 Guidelines for treatment
of sexually transmitted diseases. Morbid Mortal Wkly Rep 1997;47:79.
Miller KE: Sexually transmitted diseases. Women's Health 1997;24:179.
2001
McGraw-Hill
Tract
Infections
16
Urinary
Tract
Infections
Walter R. Wilson MD
Nancy K. Henry PhD, MD
COMMUNITY-ACQUIRED
TRACT
INFECTIONS
Essentials
Acute
of
URINARY
Diagnosis
Cystitis-Urethritis
Acute
Pyelonephritis
Acute
age
Prostatitis
(subjects
older
than
35)
Chronic
Prostatitis
prostate.
General
Considerations
bladder,
More
Frequent
Escherichia
coli
E coli
Staphylococcus
patients)
Less
Frequent
Other Enterobacteriaceae
Enterococci
Streptococcus
agalactiae
Other Enterobacteriaceae
Enterococci
Other
Community-Acquired
Children
Adults
More Frequent
E coli
E coli
Less
Frequent
Other Enterobacteriaceae
Enterococci
Infection
Other Enterobacteriaceae
Enterococci
Dysuria-Pyuria
Syndrome
Children
in
Females
Adults
Clinical
Findings
findings.
diagnosis
of
prostatitis.
Differential
Diagnosis
Complications
Uncommon or rare complications of UTI include acute papillary
necrosis, perinephric or intrarenal abscess, emphysematous
pyelonephritis, or xanthogranulomatous pyelonephritis. When
present, acute papillary necrosis is most common in diabetic
dehydrated patients with pyelonephritis and is characterized by
diminished renal function and sloughing of renal papilla. The
Antimicrobial
Acute
Therapy
uncomplicated
cystitis-urethritis
in
women.
Singe-dose
therapy. Single-dose antimicrobial therapy
results in cure rates ranging from 65100%,
depending on the antimicrobial agent administered. High
cure rates of 8595% may be achieved after therapy
with a fluoroquinolone, such as ciprofloxacin, ofloxacin,
or levofloxacin, or with trimethoprim-sulfamethoxazole.
-Lactam therapy is less effective, possibly because of
persistence of microorganisms in the periurethral and
perirectal area or because of resistance of
microorganisms to -lactams. The advantages of single-
Acute
pyelonephritis. Patients with severe infections, such
as those with nausea, vomiting, and hypotension, should be
hospitalized. Others with mild to moderate infection may be
treated as outpatients, provided that they are compliant and
are able to tolerate oral antimicrobial therapy. Antimicrobial
therapy is initially empiric and should be modified
appropriately based on the results of cultures and
susceptibilities. Effective therapy results in defervescence of
fever and other symptoms, usually within 48 h after onset of
treatment. Failure to respond may be the result of resistant
microorganisms or the presence of perinephric or intrarenal
abscess or persistence of infection in polycystic renal
disease. Antimicrobial therapy of pyelonephritis should be
administered for 14 days. Patients with acute pyelonephritis
should
P.225
P.226
have an ultrasound examination to exclude obstruction or
stones. A follow-up urine culture should be obtained 12
weeks after completion of therapy. In hospitalized patients,
parenteral therapy may be changed to orally administered
therapy when patients improve and are able to tolerate oral
therapy.
Asymptomatic
bacteriuria. Children should be treated
with antimicrobial therapy as described for those with
symptomatic infection, as shown in Box 16-2 . Aside from
pregnant women, adults, especially the elderly, do not
benefit from antimicrobial therapy.
Pregnancy. The rationale for antimicrobial therapy in these
patients is described above. The goal of treatment is to
maintain sterile urine throughout pregnancy. The
antimicrobial regimens are shown in Box 16-2 . Single-dose
therapy has not been adequately studied in these patients.
Three-day therapy may be as effective as seven-day
treatment but there are relatively few published studies with
three-day treatment of asymptomatic bacteriuria in
therapy.
Reinfection. Women with infrequent reinfection (
23 times/year) should be treated with short-course
antimicrobial therapy as if each UTI were a new, discrete
episode. Single-dose self-administered therapy taken after
sexual intercourse is usually effective to decrease the
frequency of UTI related to sexual activity. In some women
with frequent lower-tract reinfection, no precipitating event
is apparent. In these patients with symptomatic, frequent
reinfection, long-term antimicrobial therapy is warranted. If
reinfection occurs during treatment, urine culture and
sensitivity should be obtained, and the prophylactic regimen
should be changed based on the results.
Prostatitis.
Acute prostatitis. Antimicrobial therapy of acute
prostatitis in young men (< 35 years of age) should
include agents that are effective against N gonorrhoeae
and C trachomatis (Box 16-2 ). Patients older than 35
years usually have infection caused by members of the
Enterobacteriaceae. Studies suggest that the relapse
rate or development of chronic prostatitis may be higher
in patients with acute prostatitis who are treated for < 4
weeks with antimicrobial therapy. Prostatic abscess
usually requires drainage; cure with antimicrobial
therapy alone is uncommon.
Chronic
prostatitis. The selection of an antimicrobial
agent should be based on culture and sensitivity results.
Cure is difficult to achieve, and relapses are common.
Therapy with trimethoprim-sulfamethoxazole or a
fluoroquinolone results in higher drug concentrations in
prostate tissue and superior cure rates compared with
therapy with a -lactam. The presence of prostatic
calcification or stones is associated with a high failure
rate. Chronic suppressive therapy, usually with
trimethoprim-sulfamethoxazole or a fluoroquinolone or
therapy.
cephalosporin1 I V3 for 14 d
bacteriuria
Pregnancy
Amoxicillin (dosage above) or oral cephalosporin,1 o r
TMP/SMX (dosage above) or TMP, 100 mg orally twice daily,
or nitrofurantoin, 100 mg orally twice daily for 7 days.
Discontinue sulfa 2 wk before delivery. Avoid
fluoroquinolone or tetracycline use.
Adults, elderly Caused by urinary tract instrumentation
No treatment necessary
Choice of therapy depends on results of culture and
antimicrobial sensitivity. Treat for 3 d
Acute prostatitis Less than 35 years of age
Fluoroquinolone1 for 7 d
Ceftriaxone, 125 mg IM single dose, or other FDA-approved
cephalosporin1 plus either doxycycline, 100 mg orally twice
daily for 7 d or azithromycin, 1 g orally as a single dose
Older than 35 years of age
Fluoroquinolone1 or TMP/SMX, 1 DS orally twice daily for 4
wks
Chronic
prostatitis
catheter
associated
First
Choice
Second
Choice
Prognosis
Children. Children without obstruction or vesicoureteral
reflux have an excellent prognosis. Uncorrected obstruction
with infection may result in severe progressive renal
disease. Reflux, together with infection, is associated with
development of progressive renal scarring and, if untreated,
may progress to arterial hypertension and end-stage renal
disease. Eradication of bacteriuria may reduce the severity
of reflux. Mild to moderate reflux may disappear
spontaneously in older children over time, probably as a
result of maturation of the vesicoureteral junction. Surgery
may be necessary to correct severe persistent reflux
disease.
Adults. Prognosis of the large majority of adults with UTIs
is excellent. Many women with UTIs had UTIs as children. A
female who develops a UTI is more likely to develop
subsequent infections than a woman who has had no prior
UTI.
When associated with obstruction, infection may lead to
progressive renal damage and failure. Recurrent infection in
the absence of obstruction rarely, if ever, leads to
Prevention
Postcoital lower UTIs in females may usually be prevented by
administration of a single dose of an antimicrobial agent after
sexual intercourse (see above). Long-term prophylaxis should
be considered for patients who have had frequent symptomatic
relapses or recurrences of infection and are at risk of
developing progressive renal damage, such as young
with vesicoureteral reflux or patients with obstruction
For long-term prophylaxis, it is not usually necessary
administer the same dosage of an antimicrobial agent
children
or stones.
to
that has
NOSOCOMIALLY
ACQUIRED
TRACT
INFECTIONS
Essentials
Majority
of
URINARY
Diagnosis
asymptomatic.
Epidemiology
and
Microbiology
Pathogenesis
Frequent
Frequent
Escherichia coli
Other Enterobacteriaceae
Pseudomonas spp.
Staphylococcus
epidermidis
Catheter-Associated
Catheterization
More frequent
Less
Long-Term
frequent
Providencia
stuartii
Pseudomonas spp.
(>30
days)
Escherichia coli
Other Enterobacteriaceae
Staphylococcus
epidermidis
Catheter-Associated
Short-Term
Catheterization
(<30-d)
Clinical
Findings
Signs and symptoms. The majority of patients with shortterm catheterization and bacteriuria are asymptomatic.
However, 2530% of these will develop signs of UTI with
fever, suprapubic pain, or flank pain. Men are more likely to
develop bacteriuria than women. Bacteremia usually caused
by E
P.229
coli occurs in < 5% of patients with short-term
catheterization. Patients with long-term catheterization may
develop symptoms of UTI similar to those of patients with
short-term
catheterization.
Laboratory
Differential
Diagnosis
Complications
In addition, these patients may develop complications
associated with catheter obstruction, stone formation, renal
failure, or chronic pyelonephritis. Like patients with short-term
catheterization, bacteremia may occur and is usually caused by
E coli but also may be caused by P stuartii or other members of
the Enterobacteriaceae. .
Obstruction is the result of catheter plugging caused by a matrix
composed of protein, bacteria, glycocalyx, and crystals. P
mirabilis is the most common microorganism that causes
catheter obstruction and stone formation in patients with longterm catheterization. Chronic pyelonephritis is related to the
duration of catheterization. Chronic renal failure may occur,
resulting from a combination of factors that includes chronic
pyelonephritis, stone formation, and catheter obstruction.
Therapy
The use of antimicrobial therapy may delay the onset but does
not prevent bacteriuria in patients with an indwelling urinary
catheter. Moreover, long-term administration of antimicrobial
Prognosis
The prognosis for bacteriuria in patients with short-term
catheterization is excellent after removal of the catheter. The
frequency of bacteremia originating from the urinary tract in
patients with short-term catheterization is < 5%, and the
mortality related to bacteremia from nosocomial bacteriuria in
these patients is < 15%. Most deaths are related to severe
underlying
disease.
In patients with long-term urinary catheters, bacteriuria will
persist for as long as the catheter is in place and may persist
even after catheter removal, despite administration of
antimicrobial therapy. The urinary tract is the source of the
majority of febrile episodes of bacteremia in patients with long-
urinary
catheters.
Prevention
Prevention of bacteriuria may be considered as follows:
avoidance of long-term urinary catheterization, prevention of
bacteriuria once a urinary catheter is inserted, prevention of
complications of bacteriuria, and prevention of patient-topatient
transmission.
Avoidance of urinary catheterization. Methods such as
biofeedback, patient training for bladder-emptying
techniques, and the use of special clothing, including adult
diapers, may be effective in selected patients. Condom
catheters have been used in men and probably reduce the
risk of bacteriuria. Intermittent self or assisted
catheterization delays the onset of bacteriuria and may
reduce the frequency of bacteremia, febrile episodes, stone
formation, and renal disease. Suprapubic catheterization
may reduce the incidence of bacteriuria and ureteral
strictures.
Prevention of bacteriuria. Once a urinary catheter is
inserted, the major methods for prevention of bacteriuria
are to maintain a closed catheter system and to remove the
catheter as soon as possible. Irrigation of the catheter and
bladder with antimicrobial agents has not been effective in
preventing bacteriuria. The use of silver- or antibioticcoated or -impregnated urinary catheters has been
investigated.
P.230
Conflicting results have been published, and more data are
necessary to assess the efficacy of silver-coated urinary
catheters in reducing the risk of bacteriuria. Antimicrobial
agents should not be administered to patients with long-
REFERENCES
Johnson J, Stamm W: Diagnosis and treatment of acute
urinary tract infection. Infect Dis Clin North Am 1987;1:773.
Sobel JD, Kaye D: Urinary Tract Infections. In Mandel et al:
Principles and Practices of Infectious Diseases , 4th ed.
Churchill Livingstone, 1995.
2001
McGraw-Hill
Syndrome
17
Sepsis
Syndrome
Andrew D. Badley MD
James M. Steckelberg MD
Essentials
of
Diagnosis
General
Considerations
The Greek origins of the term sepsis refer to the process of putrefaction
and decay. Historically, it has come to mean the presence of pathogenic
microorganisms or their biologically active products in the host. It is the
presence of biologically active products that causes the inflammatory
from
JAMA
1995;273:155).
Clinical
Findings
blood
pressure.
TNF-
Macrophages
Vasodilation, hypotension, induces fever, induces production of acutephase reactant proteins by liver
TNF-
monocytes
T cells
Decreases arterial
Interferon-
T lymphocytes
pressure,
cardiac
ejection
fraction
decreases
coronary
Source
Dominant
Physiologic
Effects
Differential
Diagnosis
Complications
The clinical findings related to sepsis syndrome are a reflection of the
pervasive nature of the inflammatory mediators of sepsis. Virtually every
organ system is affected in sepsis syndrome, although the degree of
involvement of each organ varies widely between patients. Just as the
effects of sepsis syndrome are present in virtually every organ system so
are
potentialcomplications.
Central
Nervous
Treatment
The aims of treatment for patients with sepsis syndrome are threefold:
Elimination of the infectious agent(s) responsible for inducing sepsis.
Supportive care based in the intensive care unit aimed at normalizing
oxygenation, ventilation, blood pressure, and tissue perfusion.
Therapies intended to interrupt inflammatory mediators of sepsis.
Elimination of Infectious Agent(s). Eliminating infectious agents
often consists of administering empiric antibiotics together with
appropriate surgical drainage or dbridement. The complete
medical history and physical examination, in addition to the clinical
scenario, are used to generate a microbiologic differential diagnosis
and guide selection of empiric antibiotic therapy. Host factors that
may predispose patients to certain infections are shown in Box 17-2 .
In a critically ill patient with sepsis syndrome, several possible
microbial etiologies commonly exist. Therefore broad-spectrum
empiric antibiotic therapies are used until further microbiologic data
are available, which might indicate that a more specific antimicrobial
regimen is appropriate. Once available, culture data and sensitivity
profiles should be used to narrow the spectrum of antibiotics (often
to only one agent). The choice of initial antibiotics is based on the
likelihood of specific microorganisms for the given clinical scenario
(Box 17-3 ), and the choice of subsequent antibiotics is guided by
the results of microbiology testing.
Supportive Care. Supportive care should be based in the intensive
care unit and is aimed at normalizing oxygenation, ventilation, blood
pressure, and tissue perfusion. The principal means of achieving this
goal is aggressive fluid resuscitation, along with possible adjunctive
therapy with pressors.
Experimental
Prognosis
The proportion of patients with sepsis who develop septic shock varies
between 20% and 40%. Despite increased understanding of its
pathogenesis and advances in supportive care, the crude mortality rate
of septic shock remains between 50% and 80%.
Prevention
&
Control
Because sepsis syndrome is not one infection, there is no one thing that
can be done to prevent its development. In general, early recognition of
infection and appropriate therapy may help to prevent the development
of the sepsis cascade. For individuals
P.237
in the community, appropriate vaccinations, including pneumococcal
vaccination for patients with chronic obstructive pulmonary disease, may
help to decrease the incidence of infections and perhaps of sepsis
syndrome. For hospitalized patients, several measures may decrease the
incidence of sepsis syndrome: (1) appropriate use of prophylactic
perioperative antibiotics, (2) restriction of the use of medical appliances
pneumoniae,
Haemophilus
influenzae,
pyogenes,
Neisseria
Enterobacteriaceae,
cytomegalovirus
Staphylococcus
aureus , coagulase-negative Staphylococcus species
Chronic steroid use
Streptococcus pneumoniae, Haemophilus influenzae
Neonates
Group B Streptococcus, Listeria monocytogenes, Streptococcus
pneumoniae, Haemophilus influenzae
Posoperative
patients
Staphylococcus
aureus,
Enterobacteriaceae , nosocomial gram-negative
bacteria
Elderly
Streptococcus pneumoniae,
aureus, Enterobacteriaceae,
Host
Factor
Likely
Haemophilus influenzae,
Listeria monocytogenes
Staphylococcus
Pathogens
Community-acquired
pneumonia
Third-generation
cephalosporin1 +
azithromycin) O R doxycycline3
erythromycin2 (or
clarithromycin O R
imipenem/meropenem7
h).
8 Ticarcillin, 3 g IV every 6 h (pediatric 100 mg/kg IV every 8 h) or
piperacillin, 3 g IV every 6 h (pediatric 300 mg/kg IV divided every 6 h).
9
Suspected
Source
Empiric
Therapy
Glucocorticoids
No benefit
Antiendotoxin monoclonal antibodies
No consistent benefits, ? decreased mortality in patients with gramnegative sepsis
IL-1 receptor antagonists
No benefit
Platelet-activating
factor
No benefit
Bradykinin
antagonists
antagonists
No benefit
Nonsteroidal anti-inflammatory
No benefit
Anti-TNF antibodies
agents
No survival benefit
TNF receptor fusion proteins
No survival benefit
NOsynthetase
blockade
Under
investigation
Cell wall adhesion molecular blockade
Under
investigation
Anti-intercellular adhesion molecule antibodies
Under
investigation
Recombinant bactericidal/permeability
No data in humans
IL-10
No data in humans
Anti-LPS binding protein
No data in humans
Anti-IL-6
antibodies
No data in humans
increasing
protein
antibodies
Status
REFERENCES
2001
McGraw-Hill
> Table of Contents > Section II - Clinical Syndromes > 18 Fever of Unknown Origin
18
Fever of Unknown Origin
Julie Brahmer MD
Merle A. Sande MD
Essentials
of
Diagnosis
General
Considerations
Fever is defined as a core body temperature above the normal daily variatio
Normal body temperature is 3738C and varies by as much as 0.6C
throughout the day. The core temperature, measured orally or rectally, is
usually lowest in the morning and highest between 4:00 and 6:00PM.
Figure
necrosis factor; IFN, interferon; LIF, leukemia inhibitory factor; CNTF, ciliary
neurotropic factor; OncM, oncostatin M.
Definitions
of
FUO
The classic definition of FUO is a fever of >3 weeks' duration that is >38.3
on several occasions, the cause of which is not discovered after 1 week of
evaluation in a hospital. This definition was a functional one because it
eliminated acute causes of fevers, including acute viral infections, and, in >
90% of cases, the cause of the fever could be found. However, under curren
insurance guidelines and with newer technology available, a 1-week hospital
P.241
version of the classic FUO definition has been proposed that defines it as
documented fevers > 38.3C for > 3 weeks' duration, when the source of t
fever is not discovered during either 3 days of hospital investigation or 3
outpatient visits.
fever occurring for 8 days for which the history, physical examination,
and laboratory data fail to reveal a cause (Tables 18-1 ,18-2 , and 18-3 ).
Clinical
Findings
To diagnose the cause of an FUO, the clinician should first document the
presence of fever and its characteristics. Are there fevers, and how high do
they get? Sometimes the presence of fever is only subjective (the patient fe
warm but his or her temperature is normal). Although the fever pattern is
rarely helpful in establishing a diagnosis, a history of periodic fever spikes
suggests malaria, lymphoma, or cyclic neutropenia. Lymphoma (non-Hodgki
and Hodgkin's) can present with the classic Pel-Ebstein fever, which is
characterized by intermittent febrile periods lasting for days followed by day
weeks of afebrile periods. A reversal of the normal late-afternoon fever spik
that is, the presence of a morning fever spike, suggests tuberculosis,
disseminated Salmonella infection, and polyarteritis nodosum. Two fever spi
may occur in a 24-h period with tuberculosis or malaria. Periodic fevers (tho
that last for days to weeks and then abate or occur at regular intervals) in
children include cyclic neutropenia, familial Mediterranean fever, and a
syndrome of fever, pharyngitis, and aphthous stomatitis.
The history and physical examination are extremely important for the diagno
of an FUO because they enable the physician to focus the diagnostic studies.
The history should include family history, ethnic background, travel history,
animal exposures. The history and physical examination should
P.242
be repeated periodically if no cause of the FUO is discovered during the first
evaluation. It is also important to discontinue as many medications
(prescription and over-the-counter) as the patient can tolerate since drug
fevers are common.
Medication or toxic substances
Drug fever
Fume fever
Tick exposure
Relapsing fever
Rocky Mountain spotted fever
Lyme
disease
Animal contact
Psittacosis
Leptospirosis
Brucellosis
Toxoplasmosis
Cat-scratch
disease
Q fever
Rat-bite fever
Myalgias
Trichinosis
Subacute bacterial endocarditis
Polyarteritis
nodosa
Rheumatoid
arthritis
Familial Mediterranean fever
Polymyositis
Headache
Relapsing fever
Rat-bite fever
Chronic
meningitis/encephalitis
Malaria
Brucellosis
CNS neoplasms
Rocky Mountain spotted fever
Mental
confusion
Sarcoid
meningitis
Tuberculosis
meningitis
Cryptococcal
meningitis
Carcinomatous
meningitis
CNS neoplasms
Brucellosis
Typhoid fever
HIV
Cardiovascular
accident
Subacute bacterial endocarditis
Takayasu's
arteritis
Polyarteritis
nodosa
Rocky Mountain spotted fever
Nonproductive
cough
Tuberculosis
Q fever
Psittacosis
Typhoid fever
Pulmonary
neoplasms
Rocky Mountain spotted fever
Acute rheumatic fever
Vision disorders or eye pain
Temporal
Subacute
Relapsing
arteritis (emboli)
bacterial endocarditis
fever
Brain abscess
Takayasu's
arteritis
Fatigue
Carcinomas
Lymphomas
Cytomegalovirus
Typhoid fever
Systemic lupus
mononucleosis
erythematosus
Rheumatoid
arthritis
Toxoplasmosis
Abdominal
pain
Polyarteritis
nodosa
Abscesses
Familial Mediterranean
Porphyria
fever
Relapsing fever
Cholecystitis
Back pain
Brucellosis
Subacute bacterial
endocarditis
Neck pain
Subacute
thryoiditis
Adult Still's disease
Temporal arteritis (angle of jaw)
Relapsing
mastoiditis
Septic jugular phlebitis
1 Source: Cunha BA: Fever of unknown origin (FUO). In Gorbach SL, Bartlet
JB, Blacklow NR: Infectious
Diseases , 2nd ed. Philadelphia, WB Saunders,
1996.
Table
Skin
hyperpigmentation
Whipple's
disease
Hypersensitivity
vasculitis
Addison's
disease
Band keratopathy
Adult Still's disease
Dry eyes
Rheumatoid
arthritis
Systemic lupus erythematosus
Sjgren's
syndrome
Watery eyes
Polyarteritis
nodosa
Epistaxis
Relapsing fever
Psittacosis
Conjunctivitis
Tuberculosis
Cat-scratch
fever
Systemic lupus erythematosus
Conjunctival
suffusion
Leptospirosis
Relapsing fever
Rocky Mountain spotted fever
Subconjunctival
hemorrhage
Subacute bacterial endocarditis
Trichinosis
Uveitis
Tuberculosis
Adult Still's diease
Sarcoidosis
Systemic lupus
erythematosus
Lymphadenopathy
Lymphomas
Cat-scratch
fever
Tuberculosis
Lymphogranuloma
Epstein-Barr virus
venereum
mononucleosis
Cytomegalovirus
Toxoplasmosis
HIV
Adult Still's disease
Brucellosis
Whipple's
disease
Pseudolymphoma
Kikuchi's
disease
Mycobacterium
avium complex
Sternal tenderness
Metastatic
carcinoma
Pre-leukemias
Heart murmur
Subacute bacterial
endocarditis
Hepatomegaly
Hepatoma
Relapsing fever
Lymphomas
Metastatic
carcinoma
Alcoholic liver disease
Granulomatous
hepatitis
Q fever
Typhoid fever
Mycobacterium
avium complex
Splenomegaly
Leukemia
Lymphomas
Tuberculosis
Brucellosis
Subacute bacterial endocarditis
Cytomegalovirus
Epstein-Barr virus mononucleosis
Rheumatoid
arthritis
Sarcoidosis
Psittacosis
Relapsing fever
Alcoholic liver disease
Typhoid fever
Rocky Mountain spotted fever
Kikuchi's
disease
Mycobacterium
avium complex
Trapezius
tenderness
Subdiaphragmatic
abscess
Thigh tenderness
Brucellosis
Polymyositis
Polymyositis
rheumatica
Pyolnepositis
Relative
bradycardia
Typhoid fever
Malaria
Leptospirosis
Psittacosis
Central fever
Drug fever
Splenic tenderness
Subacute bacterial
endocarditis
Brucellosis
Salmonella
Epididymo-orchitis
Tuberculosis
Lymphoma
Brucellosis
Leptospirosis
Polyarteritis
nodosa
Epstein-Barr
virus
Spinal tenderness
Subacute vertebral
Subacute bacterial
Brucellosis
Typhoid fever
mononucleosis
osteomyelitis
endocarditis
Arthritis/joint
pain
Familial Mediterranean
Pseudogout
Rat-bite fever
fever
Rheumatoid
arthritis
Systemic lupus erythematosus
Lyme disease
Brucellosis
Hyper IgD syndrome
Calf tenderness
Rocky Mountain spotted fever
Polymyositis
Thrombophlebitis
Psittacosis
Abdominal
tenderness
Cholecystitis
1 Source : Cunha BA: Fever of unknown origin (FUO). In Gorbach SL, Bartlet
JB, Blacklow NR: Infectious
1996.
Table
Laboratory tests and evaluation should be focused by the history and physic
examination and should not be used randomly. Serial blood cultures (three
blood cultures over a 48-h period) should be drawn to detect a bacterial,
exposure.
Trichinosis
Lymphomas
Drug fever
Addison's
disease
Polyarteritis
nodosa
Hypersensitivity
vasculitis
Hypernephroma
Myeloproliferative
diseases
Leukopenia
Miliary
tuberculosis
Brucellosis
Systemic lupus
Lymphomas
Pre-leukemias
Typhoid fever
Kikuchi's
erythematosus
disease
Basophilia
Carcinomas
Lymphomas
Pre-leukemias
Myeloproliferative
diseases
Lymphocytosis
Tuberculosis
Epstein-Barr virus mononucleosis
Cytomegalovirus
Toxoplasmosis
Non-Hodgkin's
lymphoma
Pertussis
Lymphocytopenia
HIV
Whipple's
disease
Tuberculosis
Systemic lupus erythematosus
Sarcoidosis
Atypical
Lymphocytosis
Epstein-Barr virus
Cytomegalovirus
Brucellosis
Toxoplasmosis
Drug
mononucleosis
fever
Thrombocytosis
Myeloproliferative
Tuberculosis
diseases
Carcinomas
Lymphomas
Sarcoidosis
Vasculitis
Temporal
arteritis
Subacute
osteomyelitis
Hypernephroma
Thrombocytopenia
Leukemias
Lymphomas
Myeloproliferative
diseases
Relapsing fever
Epstein-Barr
virus
Drug fever
Vasculitis
Systemic lupus erythematosus
HIV
Rheumatoid factor
Subacute bacterial endocarditis
Chronic active hepatitis
Rheumatoid
arthritis
Malaria
Hypersensitivity
vasculitis
endocarditis
Carcinomas
Lymphomas
Myeloproliferative
diseases
Abscesses
Subacute
osteomyelitis
Polymyositis
Hyper IgD syndrome
Elevated
alkaline
phosphatase
Hepatoma
Miliary
tuberculosis
Lymphomas
Epstein-Barr virus mononucleosis
Cytomegalovirus
Adult Still's disease
Subacute
thyroiditis
Temporal
arteritis
Hypernephroma
Polyarteritis
nodosa
Liver
metastases
Granulomatous
hepatitis
Mycobacterium
avium complex
Increased serum transaminases
Epstein-Barr virus mononucleosis
Cytomegalovirus
Q fever
Psittacosis
Drug fever
Leptospirosis
Toxoplasmosis
Brucellosis
Relapsing fever
Kikuchi's
disease
Idiopathic
granulomatosis
Alcoholic
hepatitis
Abnormal renal-function tests
Subacute bacterial endocarditis
Renal
tuberculosis
Polyarteritis
nodosa
Fabry's disease
Leptospirosis
Brucellosis
Lymphomas
Systemic lupus
erythematosus
Hypernephroma
HIV
Malakoplakia
1 Source : Cunha BA: Fever of unknown origin (FUO). In Gorbach SL, Bartlet
JB, Blacklow NR: Infectious
1996.
Table
Differential
Diagnosis
Mycobacterium
avium complex, and fungal infections. In contrast, the major
causes of FUOs in elderly patients are malignancy and collagen vascular
disorders, followed by occult infections.
these are respiratory tract infections. Of FUOs in children, ~ 13% are caused
connective tissue diseases, and ~ 6% are caused by neoplasia.
Malignancy
Lymphoma
Metastases to liver/CNS
Hypernephromas
Hepatomas
Pancreatic
carcinoma
Preleukemias
Atrial myxomas
CNS tumors
Myelodysplastic
diseases
Infections
Extrapulmonary tuberculosis (Renal TB, TB meningitis, Miliary TB)
Intraabdominal abscesses (subdiaphragmatic abscesses:
Periappendiceal
Pericolonic
Hepatic)
Pelvic abscesses
Subacute bacterial endocarditis
Mycobacterium
avium complex (AIDS)
Permanently placed central IV line
Colon carcinoma
Cytomegalovirus
Toxoplasmosis
Salmonella enteric fevers
Intra/perinephric
abscesses
Dental abscesses
HIV
Cryptococcosis
Small brain abcesses
Chronic sinusitis
Subacute vertebral osteomyelitis
Chronic subacute vertebral
osteomyelitis
Listeria
Yersinia
Brucellosis
Relapsing fever
Rat-bite fever
Chronic Q fever
Cat-scratch fever
Epstein-Barr virus
(elderly)
Malaria
Leptospirosis
Blastomycosis
Histoplasmosis
Coccidioidomycosis
Infected aortic aneurysms
Infected vascular graft
Rocky Mountain spotted fever
Lyme disease
Leishmaniasis
Trypanosomiasis
Trichinosis
Prosthetic device
Relapsing
mastoiditis
Septic jugular phlebitis
Rheumatologic
Still's disease (adult juvenile rheumatoid
arthritis)
hypersensitive
fever
Drug fever
Cirrhosis
Alcoholic hepatitis
Granulomatous
hepatitis
Pulmonary emboli (multiple,
Regional enteritis
Whipple's disease
Fabry's disease
recurrent)
Hyperthyroidism
Hyperparathyroidism
Pheochromocytomas
Addison's disease
Subacute
thyroiditis
Cyclic
neutropenias
Polymyositis
Wegener's
granulomatosis
Occult hematomas
Weber-Christian
disease
Sarcoidosis (eg, basilar meningitis,
hepatic
granulomas)
Hypothalamic
dysfunction
Habitual
hyperthermia
Factitious fever
Giant hepatic hemangiomas
Mesenteric
fibromatosis
vasculitis)
Pseudolymphomas
Idiopathic
granulomatosis
Kikuchi's disease
Malakoplakia
Hyper IgD syndrome
1 Source : Cunha BA: Fever of unknown origin (FUO). In Gorbach SL, Bartlet
JB, Blacklow NR: Infectious
Diseases , 2nd ed. Philadelphia, WB Saunders,
1996.
Common
Table
Uncommon
Rare
Definition
Not in other categories fever 3 weeks
ANC < 500
Classic only in patients
HIV-positive
patients
Hospitalized and not infected on admission
Fevers 8 days in < 18-year-old patients
Duration of investigation
3 Days as inpatient or 3 outpatient visits
3 Days as inpatient
Same as classic FUO
3 Days as inpatient or 4 wks as outpatient
3 Days
Not defined
Most common causes
Infection
Malignancy
Collagen-vascular
diseases
Drugs
Fungal infection
Perianal infection
Bacterial
infection
Drugs
Underlying disease
Malignancy
Infection
Collagen-vascular
Drugs
diseases
diseases
Classic
Neutropenic
Elderly
HIV
Nosocomial
Pediat
HIV-Positive
Patients. In HIV-positive patients with an FUO, other
specialized testing should be performed. The differential diagnosis for H
related FUOs consists of mainly infectious causes such as tuberculosis,
Mycobacterium
avium complex, and disseminated fungal infections.
Neoplasms such as lymphomas also cause FUOs in AIDS patients.
Tuberculosis is a common cause, especially if the CD4 count is high. If t
CD4 count is significantly decreased (< 100), atypical mycobacteria, ma
Mycobacterium
avium , are the most common Mycobacterium species
causing fever. Therefore work-ups of FUOs in AIDS patients should focus
those diagnoses.
Blood cultures should be done for bacteria, fungi, and mycobacteria. A
can cause FUOs because the classical physical findings may be absent an
the leukocyte count normal. Tuberculosis is also a significant cause of FU
in the elderly. Other diseases such as sarcoidosis, lupus, Still's disease,
factitious fevers are more common in younger patients.
Treatment
Empiric drug trials should be used with extreme caution and should not take
place of a thorough investigation for the cause of the FUO, especially if an
infection is suspected. If malignancy is strongly suspected, a trial of naprox
can be tried. If investigations for an FUO in an HIV-positive patient are not
successful in finding the cause, an empiric trial of antimycobacterial therapy
may be useful. However, empiric treatment has not been evaluated
scientifically. Neutropenic patients are the only group in which empiric broad
P.246
(see Chapter 26 ). Empiric therapy for neutropenic patients classically includ
ceftazidime and an aminoglycoside; however, this may vary depending on
REFERENCES
Cunha BA: Fever of unknown origin. Infect Dis Clin North Am 1996;10:111
Cunha BA: Fever of unknown origin in the elderly. Geriatrics 1982;37:30.
Gleckman RA, Esposito AL: Fever of unknown origin in the elderly: diagnos
and treatment. Geriatrics 1986;41:45.
Konecny P, Davidson R: Pyrexia of unknown origin in the 1990s: time to
redefine. Br J Hosp Med 1996;56:21.
Long SS (editor): Principles and Practice of Pediatric Infectious Diseases ,
Churchill Livingstone, 1997.
Petersdorf RG, Beeson PB: Fever of unexplained origin: report on 100 case
Medicine
1961;40:1.
2001
McGraw-Hill
> Table of Contents > Section II - Clinical Syndromes > 19 Fever & Rash
19
Fever & Rash
Peter K. Lindenauer MD, MSc
Merle A. Sande MD
Essentials
of
Diagnosis
General
Considerations
PATIENT
Drug
HISTORY
Use
Diet
Diet is occasionally found to be the cause of fever
P.248
and rash. Food allergies to such substances as eggs, nuts,
chocolate, and shellfish can cause both immediate,
Figure
Contacts
Contacts with sick individuals or with animals are important
modes of transmission for many of the diseases that can cause
fever and rash (Box 19-1 ). Viral illnesses are commonly
transmitted this way, especially the classic childhood exanthems
varicella zoster, rubella, measles, fifth disease
(erythema infections resulting from parvovirus B-19), along with
mononucleosis and cytomegalovirus. Bacterial infections,
notably streptococcal and meningococcal, are usually associated
with contact with an afflicted individual. Sexual contact is a
mode of transmission of hepatitis B and is the source of
gonococcal, chlamydial, and syphilis infection. Acute HIV
infection obtained sexually or through injection drug use often
presents with fever, pharyngitis, and generalized rash.
Insect
and
Animal
Exposure
who are
splenectomy.
should raise the
is seen in patients
Travel
Travel to endemic regions is usually described in cases of
coccidioidomycosis and in viral hemorrhagic fever and scrub
typhus. Malaria may present in travelers returning from an
endemic area, and severe Plasmodium
falciparum infections
should be considered for those with petechial rashes
accompanied by hemolysis, thrombocytopenia, and acute renal
failure.
Occupational
Exposure
Prior
Medical
History
P.249
for the development of many of the infections previously
discussed. Patients with a prior history of rheumatologic
diseases or inflammatory bowel disease are often subject to
flares that can include fever and rash as part of the
presentation.
More
Frequent
Varicella
Enteroviruses
Epstein-Barr virus
Parvovirus B-19
Group A sterptococci4
Sepsis
Other viruses
Sepsis 2
Infective
Varicella
Neisseria
Less
endocarditis3
zoster
meningitidis
Frequent
Neisseria
meningitidis
Borellia
burgdorferi
Measles
Rickettsia
rickettsii
Rickettsia
rickettsii
Borellia
burgdorferi
T pallidum
Plasmodium
falciparum
Disseminated fungal disease
Salmonella typhi
Dengue
1
and Pseudomonas
aeruginosa .
3 Infective endocarditis most commonly caused by viridans
streptococci. Parenteral drug users and hospitalized patients
with vascular catheters are at high risk of Staphylococcus
aureus endocarditis.
4 Scarlet fever in association with group A streptococcal
pharyngitis.
Children
Adults
SEASON
&
GEOGRAPHIC
SETTING
SPECIAL
POPULATIONS
HOSPITALIZED
&
IMMUNOSUPPRESSED
PATIENTS
HIV-INFECTED
PATIENTS
and
aseptic
meningitis.
Dermatologic
P.250
Clinical
Findings
by a diffuse
a severe
typically
diffuse
parvovirus B-19,
hepatitis B, roseola,
Rickettsial
Rocky Mountain spotted fever (early), murine and scrub
typhus
Fungal
Disseminated
candidiasis,
coccidioidomycosis,
histoplasmosis,
blastomycosis,
sporotrichosis
Other
Drug reactions, serum sickness, erythema multiforme,
systemic lupus erythematosus, dermatomyositis,
Behet's disease,
bowel disease
Vesicles
Bacterial
Reiter's
syndrome,
inflammatory
Other
Drug reactions, Henoch-Schnlein
thrombocytopenic
purpura
Rash
Table
Category
Type
purpura,
thrombotic
Cause
Figure
19-2.
Enterovirus.
Figure
Petechial,
Figure
P.252
Distribution. The distribution of the rash may also aid
in diagnosis. A macular or petechial rash involving the
palms or soles should suggest Rocky Mountain spotted
fever, meningococcemia, infective endocarditis,
Mycoplasma infection, scarlet fever, or bacteremia. The
lesions of secondary syphilis, atypical measles,
Kawasaki's disease, and many drug exanthems may
present similarly. Maculopapular rashes caused by
viruses usually spare the palms and soles, whereas
these sites may be involved in vesicular exanthems
caused by herpesvirus and certain coxsackie virus
Differential
Diagnosis
Stevens-Johnson
Immediately
syndrome.
Life-threatening
Meningococcemia
Rocky Mountain spotted fever
Bacterial or candidal sepsis syndromes
Infective
endocarditis
Toxic shock syndrome
Toxic streptococcal syndromes
Staphylococcal scalded skin syndrome
Stevens-Johnson
syndrome
Treatable
Infectious
Infectious
Enteroviral
infections
Classic childhood exanthems
Hepatitis B
Epstein-Barr virus
Cytomegalovirus
Dengue
Viral hemorrhagic fevers
Noninfectious
Adverse drug reactions
Rheumatologic disorders [systemic lupus erythematosus,
dermatomyositis, Behet's disease, Reiter's syndrome,
Still's disease, vasculitis (various forms)]
Serum sickness
Thrombotic thrombocytopenic
Henoch-Schnlein
purpura
purpura
Possible
Causes
Figure
Complications
Complications relate to the specific pathogen responsible for the
syndrome of fever and rash, and no complications are common
to the group. Patients with meningococcemia are at risk for the
development of the sepsis syndrome, disseminated intravascular
coagulation, or death unless appropriate antibiotics are
promptly begun. Rocky Mountain spotted fever is a multisystem
disease that can cause encephalitis in approximately one
quarter of cases. Infective endocarditis, if left untreated, rapidly
progresses and is associated with valve destruction and
incompetence as well as complications from septic emboli, such
as stroke. Toxic shock syndrome is associated with profound
hypotension, and it is this aspect of the illness that results in
the vast majority of its complications. The complications from
toxic epidermal necrolysis and staphylococcal scalded skin
syndrome relate primarily to the degree of epidermal necrosis
and include metabolic derangement and severe
immunosuppression.
Treatment
Treatment of fever and rash may be specific (as in the case of a
Prognosis
Mortality in patients with fever and rash is closely tied to the
organism or process responsible for the syndrome and to the
timeliness of recognizing and instituting appropriate therapy.
First
Choice
Acquired
Hospital
Acquired3
Prevention
and
Control
REFERENCES
Lindenauer PK, Sande MA: Fever and rash. In Stein JH:
Internal Medicine , Mosby, 1998.
Meyers SA, Sexton DJ: Dermatologic manifestations of
arthropod-borne diseases. Infect Dis Clin North Am
1994;8(3):689.
McCauliffe
DP,
Sontheimer
RD:
Dermatologic
manifestations
2001
McGraw-Hill
Diarrhea
20
Infectious
Diarrhea
Essentials
of
Diagnosis
Most enteric pathogens are acquired by the fecal-oral route with food or
water. Other risk factors include antibiotic use, travel to the developing
world, AIDS, and institutional care.
General
Considerations
common problem among all age groups. Moreover, epidemiologic events suc
as the AIDS epidemic, the globalization of the food supply, and emergence o
new pathogens are increasingly factors in diarrheal illnesses. Chlorine-
resistant Cryptosporidium
parvum now threatens our drinking water,
Cyclospora
cayetanensis and EHEC menace our food supply, and toxigenic C
difficile increasingly is a problem in hospitalized and institutionalized patient
Given the ubiquitous nature of infectious diarrhea, it is imperative that prim
care physicians and infectious disease specialists have a firm understanding
the diagnosis and treatment of these diverse and potentially devastating
illnesses.
and 3.2 illnesses per child per year (up to 5.0 illnesses per child per yea
for children in day care). However, adults and especially the elderly are
not spared. The elderly population especially is at risk for the more serio
sequelae of infectious diarrhea, and most of the mortality related to
gastroenteritis in adults occurs in this group.
P.256
agent. Contaminated food or water ingestion, recent travel, antibiotic us
HIV positivity or AIDS, and institutional or day care all are important clu
to identify the patient who may be at increased risk for developing
infectious
diarrhea.
Contaminated
food supply is a major problem both in the developing world and in the
United States, where 400600 documented food-borne outbreaks and
millions of cases are estimated to occur each year. A number of foods an
pathogens have been associated with food-borne diarrheal illnesses: raw
or poorly cooked shellfish (Vibrio
parahemolyticus , Norwalk virus),
chicken (Campylobacter
jejuni; see Chapter 57 ), eggs (Salmonella
enteriditis; see Chapter 53 ), chocolate milk (Listeria
monocytogenes; s
Chapter 51 ), reheated fried rice (Bacillus cereus; see Chapter 51 ), and
undercooked beef, unpasteurized apple cider, lettuce, and alfalfa sprouts
(EHEC; see Chapter 53 ). The mode of food contamination is varied; an
infected food handler with poor hygiene, untreated human or animal was
used as fertilizer, unclean water used to wash or prepare food, and anim
feces mixing with meat products during or after slaughter all have been
increasing proportion of meals are now prepared outside the home (eg,
restaurants), exposing large numbers of people to common source
outbreaks related to, for example, an infected food handler or
contaminated foodstuffs. Finally, the intentional contamination of the foo
supply by diarrheal pathogens has emerged as a form of biological
terrorism. One incident in the United States involved > 700 cases of
Salmonella gastroenteritis related to the intentional contamination of
restaurant salad bars with Salmonella
typhimurium. This criminal act wa
committed by a religious commune in an apparent attempt to influence
voter turnout for a local election.
Contaminated
Water. Drinking water, often contaminated by human or
animal fecal waste, is a common mode of acquisition of diarrheal
unfiltered water from these sources. In the past, municipal water supplie
in the United States were generally considered free from diarrheal
pathogens because of modern chlorination and filtering procedures.This
notion was challenged in 1993 when a large water-borne outbreak of
infectious diarrhea in Milwaukee was caused by the parasite
Cryptosporidium
parvum. This outbreak affected > 400,000 people desp
the use of standard purification procedures; further outbreaks have
occurred despite even more stringent filtration standards.
HIV and AIDS. HIV-positive and AIDS patients are at significant risk for
diarrheal illnesses. More than 30 million patients are believed to be
infected with HIV worldwide, and it has been estimated that 5090% o
these patients will develop a significant diarrheal illness at some point,
especially as the CD4 count drops below 200. Depending on the pathoge
onset can be delayed for several weeks after the antibiotic has been
stopped. Virtually all antibiotics have been implicated as a cause;
clindamycin has the highest risk with 1020% of patients who receive
antibiotics developing antibiotic-associated diarrhea, but penicillins and
cephalosporins are the most important culprits given their widespread u
Clinical
Findings
approaching the patient who may have infectious diarrhea. Clues in the hist
are very helpful in assessing the severity of the patient's illness, narrowing
differential diagnosis of potential pathogens, and choosing an appropriate
therapeutic
course.
pathogens
or
noninfectious
causes.
decreased urine output, increased thirst, and the ability of the patient to
take oral fluids. For viral infections and certain types of bacterial food
poisoning, prominent nausea and vomiting may be a clue to the diagnos
High-grade fever is more common with pathogens that invade or disrupt
infection).
The key to examining the patient with diarrhea is to assess the hydration
status and determine if there has been significant volume loss. Supine a
standing blood pressure and pulse rates should be determined to assess
for orthostatic hypotension. Supine hypotension and resting tachycardia
can indicate life-threatening hypovolemia and the need for aggressive fl
resuscitation. The mucous membranes should be assessed for moisture a
the skin for tenting. In infants, lethargy, dry mucous membranes, flat
fontanelles, sunken eyes, poor capillary refill, and poor skin turgor may
be clues of significant hypovolemia.
Laboratory
Findings. The lab evaluation of suspected infectious diarrh
should begin with testing of the stool for the presence of fecal leukocyte
The stool normally does not contain fecal leukocytes, and if present, the
are considered a marker for colonic inflammation secondary to both
infectious and noninfectious causes. This test can be performed easily at
the bedside using a stool smear stained with methylene blue or it can be
done by the microbiology lab in most hospitals. Because the neutrophils
will
P.258
degenerate with time, the sample should be examined as soon as possib
In most series, the sensitivity of the fecal leukocyte test for various
inflammatory pathogens (Salmonella,
Shigella , and Campylobacter spp.)
detected by stool culture varies from 45% to 95% depending on the
pathogen (most sensitive for Shigella spp.).
lactoferrin testing for this purpose are obvious from looking at their
respective sensitivities and specificities. However, as long as the clinicia
recognizes these limitations and interprets the results in the context of t
clinical setting, fecal leukocyte or lactoferrin tests should remain import
tools in approaching the patient with infectious diarrhea.
For hospitalized patients, the use of routine bacterial stool cultures and
parasite examinations should be governed by the 3-day rule for
bacterial cultures and the 4-day rule for parasite exams recently
advocated by the College of American Pathologists. These rules are base
on several studies showing that the yield of such tests is extremely low
patients who develop diarrhea after being hospitalized for > 34 days
and such tests are not cost effective. The pathogens that are detected b
these tests are uncommonly acquired in the hospital setting in the Unite
States. However, the application of these rules should be flexible and al
for those cases where, after careful clinical consideration, potential
If the diarrhea persists for > 7 days or if the history raises the possibilit
Unfortunately, the O+P exam can have a low yield, so consideration sho
be given to using one of the pathogen-specific tests noted above.
A history of recent antibiotic use or hospitalization in a patient with
diarrhea should raise the concern of C difficile , and the stool should be
tested for the presence of C difficile toxins. The gold standard assay is t
stool-cytotoxin test, looking at the ability of toxin B to induce cytopathic
effects in cultured cells. It is 94100% sensitive and 99% specific.
Several new immunoassays are now available that are cheaper and faste
than the stool-cytotoxin assay, but also less sensitive and specific. Seve
stool samples should be tested over sequential days before completely
excluding C difficile infection.
P.259
not helpful or indicated in the evaluation of infectious diarrhea except
inspecific cases. Severe C difficile colitis may lead to toxic megacolon an
the associated risks of intestinal perforation. Patients with C difficile col
Differential
colitis)
or
pathology
consistent
with
Diagnosis
The most important question in managing the patient with suspected infectio
Figure 20-1 outlines a general approach to the patient with infectious diarrh
using the history and the presence or absence of fecal leukocytes or lactofe
to classify the diarrhea as noninflammatory or inflammatory. Unfortunately,
there are no prospective studies that validate this algorithm by showing a
decrease in morbidity or mortality. However, keeping in mind the limitations
fecal leukocytes or lactoferrin as previously discussed, it is useful to begin t
formulate the differential diagnosis and to guide therapy. Box 20-1 lists the
common pathogens causing inflammatory and noninflammatory diarrhea,
day care setting. Shigella sonnei accounts for 6080% of cases in the
United States and less commonly causes bloody stools. Shigella flexerni
most common in the developing world and is more frequently associated
with grossly bloody stools. Other pathogenic species include Shigella
P.262
EHEC are Shiga toxin-producing E coli that are an emerging diarrheal
pathogen. The intestines of cattle appear to be the major reservoir of th
Figure
developing world. In the United States, the disease is most common alon
the Atlantic and Gulf coasts. The consumption of improperly cooked crab
and shrimp meat and exposure to contaminated seawater (including the
use of seawater to clean cooking utensils on cruise ships) are the main
vehicles for disease transmission. In the United States, acute self-limite
outbreaks are the rule, with explosive watery diarrhea and cramping
abdominal pain developing within 24 h after exposure and lasting for up
several days. The organism will not grow on routine stool cultures; the
diagnosis requires that the organism be isolated on thiosulfate citrate bi
salts sucrose agar.
should
reveal
the
characteristic
intranuclear
inclusions.
unformed stools per day) and cramps. The symptoms usually resolve ove
several days or < 12 days if treated early with effective antimicrobia
agents. An unfortunate minority will have disease that lasts longer than
week. Fever and bloody stools are uncommon.
Mycobacterium
P.263
avium complex (Chapter 62 ) is a common cause of
hosts develop diarrhea, cramps, and weight loss lasting for days to week
before resolving. Low-grade fever occurs in 50% of infected individuals.
AIDS patients, the organism can cause a severe chronic diarrhea and
biliary tract infections. The diagnosis is made by identifying the cysts by
modified acid-fast stain of the stool (often missed on routine O+P) or via
commercially
available
fluorescence
antibody
stain.
Cyclospora
cayetanensis (Chapter 83 ) is an emerging protozoal cause o
diarrhea associated with contaminated drinking water or foods (raspberr
and lettuce). Unlike Cryptosporidium spp., the life cycle of C cayetanesis
requires a maturation phase outside the host and is thus less likely to be
spread directly by person to person contact. In immunocompetent patien
after an incubation period of 1 week, a self-limited illness with watery
diarrhea, cramps, and prominent fatigue ensues. It is a rare cause of
diarrhea in AIDS patients in the United States, likely owing to the
widespread use of trimethoprim-sulfamethoxazole (TMP-SMX) prophylax
in these patients. It is, however, a common cause of diarrhea in this
population elsewhere in the world. The diagnosis is made by identificatio
of the organism on a modified acid-fast stain of the stool (not identified
Organisms
Bacteria
Bacteria
Bacteria
Bacteria
Major cause
Campylobacter
jejuni
Shigella spp.
Salmonella spp.
Enterohemorrhagic E coli 1
Clostridium
difficile
Vibrio
parahaemolyticus 2
Listeria
monocytogenes
Yersinia
enterocolitica
Enteroinvasive E coli
Enteroaggregative E coli
Viruses
Cytomegalovirus
Protozoa
Entamoeba
histolytica
Staphylococcus
aureus
Bacillus cereus
Clostridium
perfringens
Enterotoxigenic E coli
Vibrio cholerae
Mycobacterium
avium -complex
Aeromonas
hydrophila
Plesiomonas
shigelloides
Viruses
Rotavirus
Enteric adenovirus
Caliciviruses
Norwalk virus
Cytomegalovirus
Protozoa
Cryptosporidium
parvum
Giardia lamblia
Cyclospora
cayetanensis
Isospora belli
Microsporidia spp.
Enterohemorrhagic E coli
Shigella spp.
Campylobacter
jejuni
Protozoa
Entamoeba
histolytica
Campylobacter
Shigella spp.
jejuni
Salmonella spp.
Clostridium
difficile
Enteroaggregative E coli
Mycobacterium
avium -complex
Viruses
Cytomegalovirus
Enteric adenovirus
Caliciviruses
HIV enteropathy
Protozoa
Cryptosporidium
parvum
Isospora belli
Cyclospora
cayetanensis
Microsporidia spp.
Enterotoxigenic E coli
Less
common
Campylobacter
jejuni
Shigella spp.
Salmonella spp.
Rotavirus
Norwalk virus
Vibrio
parahaemolyticus
Entamoeba
histolytica
Giardia lamblia
Cryptosporidium
parvum
Cyclospora
cayetanensis
1
Inflammatory
Noninflammatory
Grossly
Bloody
Diarrhea
Diarrhea
Diarrhea
Diarrhea
in
HIV/AIDS
Traveler
Patients
Diarrhe
Complications
P.264
Malnutrition is being increasingly recognized as a major complication of
repeated or chronic diarrheal illnesses in the developing world. There is
growing evidence that children with such infections exhibit growth retardatio
and possibly cognitive dysfunction compared with matched controls. If future
studies confirm this relationship, then malnutrition may well emerge as the
most devastating long-term sequela of infectious diarrhea.
patients with E coli O157:H7 developed HUS, 50% of whom required dialysis
and had mortality as high as 1.2% (> 250 deaths per year in the United
States). The risk of developing HUS after EHEC infection appears to be
increased with the use of antimotility drugs, and these agents are
contraindicated in suspected cases. Antimicrobial therapy may increase the
risk of HUS as well, but this remains controversial.
Guillain-Barrsyndrome,
an
acute
demyelinating
polyneuropathy,
is
anothe
Treatment
As with the diagnostic approach, optimal therapy for a given diarrheal illness
should be guided by a number of different factors. The age and health of the
patient; volume status; ability to take oral fluids; presence of fever, blood,
leukocytes, or lactoferrin in the stool; and suspected pathogen all need to b
considered. For example, an adult in the United States with < 1 day of
with oral rehydration therapy, which should be used in all patients excep
those unable to take oral glucose-electrolyte solutions or who have
massive diarrhea that may require aggressive intravenous hydration to
treat life-threatening hypovolemia. Ideally, oral rehydration solutions
traveler's
diarrhea,
P.265
or V cholerae infection should be started o
decreased with antibiotic therapy and in settings where the potential for
spread is present; for example, day care is another indication for therap
suspected.
Prognosis
minimal morbidity and mortality. As with many illnesses, the morbidity and
mortality are concentrated in the very young and the elderly. In the United
States, the mortality now associated with infectious diarrhea is significantly
1.0%. There are exceptions such as EHEC infections, which had an associate
these regions to that of the developed world. The biggest improvements like
will come with changes in economic and social conditions rather than from a
further improvements in medical therapy.
Prevention
&
Control
Because most diarrheal pathogens are spread via the fecal-oral route, their
acquisition can be prevented by maintaining good personal hygiene. This
includes frequent handwashing after toilet use and especially during food
preparation. The value of good hygiene by food handlers and cooks to avoid
the spread of food-borne pathogens can not be overstated. Diapers of childr
with diarrhea should be disposed of as soon as possible with minimal
contamination
P.266
P.267
P.268
difficile
cholerae
diarrhea
lamblia
cayetanensis
belli
First
Choice
Second
Choice
Erythromycin, 12.5 mg/kg (max 500 mg) orally four times a day 5
d
Shigella/Salmonella spp.
Ampicillin, 20 mg/kg (max 500 mg) orally four times a day 5 d3
Clostridium
difficile
cholerae
diarrhea
Rehydration
Giardia
therapy
alone
lamblia
followed by iodoquinol, 10 mg/kg (max 650 mg) orally three times a day
20 d
OR
Paromomycin, 10 mg/kg (max 500 mg) orally three times a day 7 d
Tinidazole, 50 mg/kg (max 2 g) orally daily 3 d followed by either
iodoquinol
Cyclospora
or
paromomycin
cayetanensis
belli
First
Choice
Second
Choice
Because food and water are common vectors for pathogens, these areas
should be given special attention. Drinking water, water used to clean food,
water that is used in cooking should be filtered and chlorinated. If there is a
concern about water safety or if unpurified water is taken from lakes or rive
then it should be boiled for several minutes before consumption. When
swimming in lakes or rivers, people should take care not to ingest the water
Sea water is often contaminated with Vibrio species, and caution should be
exercised when using this water for cooking or washing or when swimming.
All fruits and vegetables should be washed thoroughly with clean (boiled,
filtered, or treated) water before consumption, especially given the quantity
produce now imported into the United States. Untreated human or animal
waste should not be used to fertilize fruits and vegetables. All meats and
seafood should be cooked adequately. Chicken and ground beef should be
cooked until the red or pink is gone. Only pasteurized dairy products and
juices should be consumed. A recent outbreak of EHEC was associated with
drinking unpasteurized apple cider made with apples contaminated, after
falling to the ground, by cattle feces.
Vaccines are a promising area for the prevention of infectious diarrhea, but
effectiveness and scope of the currently available vaccines are limited. At
present, vaccines are available for V cholerae , typhoid fever, and rotavirus.
The current parenteral cholera vaccine is not very effective and not
recommended for use. Newer oral cholera vaccines based on the toxin Bsubunit or inactivated whole cells are more effective, and the immunity is of
requires only 1 dose and has fewer side effects. An oral, live-attenuated
typhoid vaccine is available, requiring 1 capsule every other day for 4 doses
and having an efficacy similar to that of the other two vaccines. The recently
approved oral rotavirus vaccine covers serotypes 14 and is given to infan
at 2, 4, and 6 months of age. In several international trials, the vaccine
REFERENCES
Choi SW et al: To culture or not to culture: fecal lactoferrin screening for
inflammatory bacterial diarrhea. J Clin Microbiol 1996;34:928.
Dupont H et al: Guidelines on acute infectious diarrhea in adults. Am J
Gastroenterol
1997;92:1962.
Griffin P: Escherichia coli O157:H7 and other enterohemorrhagic E coli. In
Blaser M et al: Infections of the Gastrointestinal Tract. Raven, 1995.
Guerrant R: Lessons from diarrheal illnesses: demography to molecular
pharmacology. J Infect Dis 1994;169:1206.
Gueirent RL,0 von Gilder T, et al: Practice guidelines for the management
of infectious diarrhea. Clin Infect Dis 2001; 32:331.
Fekety R: Guidelines for the diagnosis and management of Clostridium
difficile -associated diarrhea and colitis. Am J Gastroenterol 1997;92:739.
Hines J, Nachamkin I: Effective use of the clinical microbiology laboratory
for diagnosing diarrheal diseases. Clin Infect Dis 1996;23:1292.
Mackenzie W et al: A massive outbreak in Milwaukee of Cryptosporidium
infection transmitted through the public water supply. N Engl J Med
1994;331:161.
2001
McGraw-Hill
Infections
21
Hepatobiliary
Infections
Paul B. Eckburg MD
Jose G. Montoya MD
Essentials
of
Diagnosis
histolytica , or
General
Considerations
sepsis
pneumonia
Listeriosis
Toxic shock
Legionnaires'
syndrome
disease
Brucellosis
Fitz-Hugh-Curtis
Salmonellosis
Nocardiosis
syndrome
Syphilis
Lyme disease
Leptospirosis
Psittacosis
Tuberculosis
Hansen's disease
Tularemia
Rickettsial
Q fever
(Leprosy)
cholelithiasis).
Disease
Table
VIRAL
Essentials
of
HEPATITIS
Diagnosis
elevation
in
aminotransferase
levels.
General
Considerations
effects.
Clinical
Findings
1%
<1%
1015%
1% (1020% in pregnancy)
Diagnostic
serology
HAV Ab (IgM)
HBsAg and HBcAb (IgM)
HCV Ab and HCV RNA
HDV Ab and HBcAB (IgM in coinfection, IgG in superinfection)
HEV Ab (IgM)
Progression to chronicity
None
90% neonates, 15% adults
80%
Nearly 100% if superinfection of chronic HBV
None
1
HAV
HBV
HCV
HDV
HEV
Laboratory
findings. Aminotransferase levels are typically > 300
U/L and often > 10002000 U/L. Elevated aminotransferases may
be discovered on routine testing in asymptomatic patients. Moderately
elevated bilirubin and alkaline phosphatase levels occur during the
icteric phase and may persist after normalization of the
aminotransferases. Leukocytosis is uncommon; however, a relative
leukopenia may be seen. Urinalysis may reveal a mild proteinuria and
bilirubinuria during the icteric phase.
Serology for the specific viral antibodies and antigens is key to
making the correct diagnosis (see Chapter 39 ). In acute hepatitis A,
HAV IgM is the most important diagnostic test. This antibody appears
early in the disease, peaks within the first week of illness, and
disappears in 36 months (HAV IgG may persist for years).
Differential
Diagnosis
Treatment
Only supportive and symptomatic treatment is available. No specific
antiviral agents have been shown to be useful in this syndrome, and there
is no benefit of corticosteroid therapy. Patients should avoid hepatotoxic
medications, alcohol, and narcotic agents. Those with fulminant hepatitis
should be hospitalized for intensive monitoring and correction of
coagulopathy. Limited studies in the treatment of acute hepatitis C with
interferon- (IFN-) suggest a reduction in the risk of chronic
hepatitis; however, this should be considered experimental at this time.
This approach is impractical for HBV because > 95% of infected adults
have self-limited hepatitis.
Prevention
Hand washing, needle precautions, and protected intercourse are
important in preventing disease. Continued screening of blood donors and
blood products may further reduce the frequency of blood-borne
infections. Vaccines and immune globulin are available for the prevention
and postexposure prophylaxis of HAV and HBV infection. HAV vaccination
is recommended for those planning travel to endemic areas, and is
available as Havrix (1.0 mL intramuscularly) or Vaqta (0.5 mL
intramuscularly). HAV Ig is indicated for all close contacts (ie, household
contacts) of known HAV-infected individuals, given as a 0.02 mL/kg
intramuscular injection within the incubation period. HBV vaccine
(Recombivax-HB or Engerix-B) is now universally recommended for all
infants and high-risk adults, and is given in a series of three injections, at
0, 1, and 6 months. HDV is also best prevented by this vaccine.
Postexposure prophylaxis with HBV Ig should be administered as early as
Prognosis
Patients with acute viral hepatitis usually recover within 316 weeks of
clinical illness. It is not uncommon for abnormal hepatic biochemical tests
to persist longer. Overall mortality is < 1%. HAV and HEV do not have
chronic carrier states, although HAV infection may persist up to 1 year
with the potential for relapses before complete recovery. HEV infection
during pregnancy is associated with a higher mortality. HBV infection is
associated with a higher mortality if there is an associated HDV infection,
and superinfection of HDV invariably leads to chronic infection. Chronic
hepatitis B occurs in 90% of infected infants and 15% of adults.
Chronic HCV infection occurs in 80% of all cases, with 30%
progressing to cirrhosis.
CHRONIC
VIRAL
Essentials
of
Possible
levels.
malaise,
HEPATITIS
Diagnosis
fatigue,
weakness,
and
elevated
aminotransferase
General
with
characteristic
hepatocellular
necrosis
Considerations
remission.
Unlike HBV, HCV infection does not involve integration into the host
genome (there is no DNA intermediate in its life cycle). Persistence of the
virus results from a high mutation rate during replication, with production
of quasispecies and avoidance of the host immune response. Of acute
HCV cases, 80% develop chronic disease.
Clinical
Findings
+
+
+
+
Chronic HBV with high infectivity
+
+
+
+
Chronic HBV with low infectivity
+
+
-
HCV
+
+
+
Superinfection of HDV on chronic HBV
+
+
+
Chronic HCV and distant acute HBV
+
False-positive HCV antibody or recovery after acute HCV
H Bs
H Bc
Ab
H Be
H Be
Ag
(IgG)
Ag
Ab
Table
HBV
HCV
Ab
HDV
HCV
DNA
(IgG)
Ab
RNA
Interpretation
Treatment
Despite similarities in clinical and histopathologic characteristics, chronic
viral hepatitis caused by HBV or HCV responds differently to therapy. IFN is the only effective treatment for both hepatitis C and B.
IFN- induces the clearance of HBV by enhancing the host immune
response. Of chronic hepatitis B cases, ~ 33% enter remission (negative
H Be Ag) after a 4- to 6-month course of IFN. This therapy is indicated
only when the patient has persistent elevations in aminotransferases, HBe
Ag, and HBV DNA. Patients with normal aminotransferase levels respond
poorly to IFN therapy (eg, Asian patients who acquired the disease in
childhood). Liver biopsy is recommended before treatment to assess
severity of fibrosis and cellular injury. IFN- is administered over a 4- to
6-month course (Box 21-1 ). Patients with concomitant chronic HDV
require higher and longer doses of IFN (9 million units thrice weekly for
12 months), which leads to a sustained response in only 1525% of
cases. In addition to IFN-, long-term suppressive therapy with
nucleoside analogs (eg, lamivudine) may prove to be beneficial in
achieving sustained inhibition of HBV replication. Lamivudine is approved
for treatment of chronic HBV with evidence of active replication
(administered 100 mg orally daily for 1 year). However, long-term
treatment may lead to the emergence of resistant mutant virus.
IFN- is also recommended for patients with chronic HCV (Box 21-1 ).
Therapy lasting 6 months may lead to remission of disease in 50% but a
sustained response in only 1025%. Long-term response is unlikely if
Chronic Hepatitis C4
Prognosis
GRANULOMATOUS
Essentials
of
HEPATITIS
Diagnosis
symptoms
Characteristic
granulomas
General
or
on
asymptomatic.
liver
biopsy
histopathology.
Considerations
Clinical
Findings
disease
Lepromatous
leprosy
Brucellosis
Listeriosis
Bartonellosis
Secondary or tertiary syphilis
Tularemia
Rickettsial
Q fever
Viral
Cytomegalovirus
infection
Infectious
mononucleosis
Fungal
Histoplasmosis
Coccidioidomycosis
Candidiasis
Cryptococcosis
Parasitic
Schistosomiasis
Visceral larva migrans
Fascioliasis
Toxoplasmosis
Table
Differential
Diagnosis
Treatment
Treatment of infectious causes of granulomatous hepatitis is directed
toward the specific cause. Granulomas seem to resolve as the systemic
infection clears. Corticosteroids have been shown to be efficacious in
some cases of idiopathic granulomatous hepatitis. However, some experts
recommend an empiric trial of two-drug antituberculous therapy before
steroid administration, given the frequency of false-negative cultures for
tuberculosis and the potential for disseminated tuberculosis with steroid
therapy. Treatment response should be monitored by clinical parameters
and repeat biopsy at 612 months.
HEPATIC
1.
ABSCESS
PYOGENIC
Essentials
of
LIVER
ABSCESS
Diagnosis
hepatomegaly.
General
Considerations
Despite frequent exposure of the liver to bacteria in both the portal and
systemic circulatory systems, the development of pyogenic liver
abscesses is rather rare. The extensive network of reticuloendothelial
cells in the hepatic sinusoids is highly protective. Hepatic abscess
formation can occur when this defense system is overwhelmed, by
bacterial invasion from either the biliary tree (eg, acute cholangitis), the
portal vein (pyelephlebitis), the hepatic artery, direct trauma, or adjacent
bacterial infection. The incidence of pyogenic liver abscess is ~ 15
cases/100,000 hospital admissions, and over one-third of such cases are
secondary to direct extension from a biliary tract infection. Bacteria less
commonly invade the liver from the portal system (eg, with appendicitis
or IBS), systemic circulation (eg, Staphylococcus
aureus abscesses in
children), or penetrating trauma (eg, complication of ventriculoperitoneal
shunt placement). Over half of liver abscesses are polymicrobic (Box 21-2
), but a single organism may be involved in abscesses from a systemic
source (eg, Candida spp. in neutropenic hosts). Either hepatic lobe may
be involved; however, the right lobe is more commonly involved given its
size and propensity to receive most portal blood flow. Abscesses may be
single or multiple, ranging from widely scattered microabscesses (eg, in S
aureus sepsis) to single large polymicrobic abscesses. Of pyogenic liver
abscesses, ~ 15% have no known cause and are classified as cryptogenic.
Clinical
Signs
rigors,
severe
shock)
Findings
and symptoms. The patient may present with high fever,
and severe right-sided abdominal pain. A more acute and
clinical picture (with fever, jaundice, abdominal pain, and
may be seen with multiple abscesses, usually associated with
Most Common
Escherichia coli
Klebsiella
pneumoniae
Proteus mirabilis
Pseudomonas
aeruginosa
Streptococcus species (e.g. S milleri )
Bacteroides
fragilis
Fusobacterium
necrophorum
Clostridium
perfringens
Peptostreptococci and microaerophilic
Staphylococcus
aureus
streptococci
Escherichia coli
Klebsiella
pneumoniae
Proteus mirabilis
Fusobacterium
necrophorum
Bacteroides
fragilis
Less Common
Salmonella typhi
Staphylococcal
species
Yersinia
enterocolitica
Burkholderia
pseudomallei
Pasteurella
multocida
Listeria
monocytogenes
Candida species
Mycobacterium
tuberculosis (eg, miliary)
Candida albicans
Salmonella typhi
Adults
Children
Differential
Diagnosis
cysts,
metastatic
carcinoma,
lymphoma,
and
infarction.
Treatment
Drainage of the abscess and IV administration of antibiotics are the
mainstays of treatment. Drainage is often done via percutaneous catheter
drainage or percutaneous needle aspiration, usually under CT or
ultrasound guidance. Recently, percutaneous needle aspiration has been
deemed as safe and effective as continuous catheter drainage; however,
repeated aspirations may be necessary in 30%. Percutaneous
drainage may not be necessary in cases with relatively small abscesses
(< 5-cm diameter), and successful treatment may be achieved with
antibiotics alone, depending on the clinical stability of the patient. Open
abdominal surgery is reserved for cases that fail to respond to
percutaneous
drainage.
Choice
Adults
Prognosis
Despite aggressive treatment, the mortality ranges from 1025%. An
increase in mortality is noted in patients with multiple abscesses,
increased age, and associated comorbid conditions. Morbidity and
2.
AMEBIC
Essentials
Fever
and
ABSCESS
of
Diagnosis
right-upper-quadrant
abdominal
pain.
General
E
histolytica.
Considerations
Clinical
Findings
P.279
pleuritic chest pain may be present when rupture into the pleural
space occurs. Diarrhea is relatively uncommon, occurring in < 30%
(despite the colon being the organism's point of entry). Jaundice and
tender
hepatomegaly
are
uncommon.
Laboratory
findings. Aminotransferase levels are variable; however,
alkaline phosphatase is usually elevated and albumin decreased.
Leukocytosis without eosinophilia is common. The erythrocyte
sedimentation rate may be elevated, and anemia may be present.
Serum antibodies to amoebae via enzyme-linked immunosorbent
assay or indirect hemagglutination assay are present in > 90% of
cases. However, serology may be negative in acute disease (but
positive on repeated testing in 710 days) and may be positive if
the patient had amebiasis in the past (as the antibody levels may
persist for years after acute infection).
Imaging. Both CT and ultrasonography are sensitive imaging studies
for diagnosis of amebic abscess, but it is difficult to distinguish
amebic abscesses from pyogenic abscesses or complex cysts. On
sonography, the abscess usually appears as a round hypoechoic lesion
near the liver capsule, with a paucity of significant wall echoes. CT
with contrast may demonstrate a well-defined low attenuation lesion
with a thick enhancing wall and surrounding zone of edema. Either CT
or ultrasonography allows for percutaneous aspiration if pyogenic
abscess needs to be ruled out. Of note, viable trophozoites are seen
only in the periphery of the abscess. Fluid from the center of the
abscess yields no organisms and varies in appearance, from yellow to
reddish-brown (anchovy paste).
Treatment
Because amebicidal therapy is highly effective, percutaneous aspiration is
not necessary. Catheter drainage should be considered only when amebic
serologies are negative, bacterial superinfection of an amebic abscess is
suspected, or a left-hepatic-lobe abscess threatens rupture into the
pericardium. Metronidazole is the drug of choice (Box 21-4 ). This must
be followed by a luminal agent, as E histolytica is present in the colon
Adults
Prognosis
Mortality caused by uncomplicated amebic abscess is < 1%. Mortality is
higher if the abscess ruptures into the peritoneum, pleural space, or
pericardium. Cure of the amebic abscess apparently results in immunity,
because recurrence in patients with positive amebic antibodies is
extremely rare.
Considerations
Fungi (Cryptococcus,
Pyogenic
Pneumocystis
carinii )
abscess
Enteric gram-negative
monocytogenes
Vascular
Histoplasma,
tuberculosis )
bacilli,
staphylococci,
streptococci, Listeria
lesions
infiltrates
Liver
Pathology
Table
Clinical
Microorganisms
Findings
Diagnostic
Approach
CALCULOUS
Essentials
of
CHOLECYSTITIS
Diagnosis
General
and
leukocytosis.
Considerations
for
Clinical
Findings
Differential
Diagnosis
Complications
Perforation of the gallbladder may occur, especially if gangrene develops
from progressive ischemia and gas-forming bacteria, including Escherichia
coli in diabetic patients and Clostridium
perfringens in emphysematons
cholecystitis. This syndrome is more common in males and diabetics, and
~ 30% of cases are associated with acalculous cholecystitis. Empyema
may result from bacterial invasion of the gallbladder wall, usually
involving enteric gram-negative bacilli and anaerobes. Treatment is
essentially the same as for acute cholecystitis; however, urgent surgical
treatment is usually indicated in patients with empyema. Repeated
episodes of acute calculous cholecystitis or chronic irritation of the gall
bladder wall by stones may lead to chronic cholecystitis. Cholangitis and
pancreatitis are potential complications if gallstones migrate and obstruct
the common bile duct or pancreatic duct.
Treatment
In most cases, acute calculous cholecystitis will subside with conservative
therapy alone. Bowel rest should be instituted and IV fluids administered.
Antibiotics are most likely required in such clinical settings as sepsis,
empyema, emphysematous cholecystitis, and cholangitis. In these
patients, antibiotic options include a -lactam/-lactamase inhibitor, a
carbapenem, ciprofloxacin plus metronidazole or clindamycin, or
trovafloxacin. Ampicillin should be used with caution, given recent
emergence of ampicillin-resistant E coli in community-acquired infections
with this organism. If urgent cholecystectomy is considered, prophylactic
antibiotics may be administered perioperatively; regimens include a
second-generation cephalosporin with moderate anaerobic activity, such
as cefoxitin or cefotetan.
Laparoscopic cholecystectomy is now considered the procedure of choice
for removal of the gallbladder. Cholecystectomy is mandatory if there is
evidence of emphysematous cholecystitis or perforation.
ACUTE
General
ACALCULOUS
CHOLECYSTITIS
Considerations
it is much
common than
common,
contrast to
3%). Patients with this syndrome are usually elderly or seriously ill and
include patients with severe burns and trauma, patients who are
recuperating from major surgery, or those receiving intensive care and
parenteral nutrition. Comorbid conditions with higher risk of developing
acalculous cholecystitis include cardiovascular disease, diabetes mellitus,
systemic arteritis (eg, polyarteritis nodosa), and immunocompromise (eg,
AIDS). The pathophysiology is poorly understood, but may be associated
with bile stasis and gallbladder dysfunction. Bile stasis and paucity of
gallbladder contractions may occur in critically ill patients and patients
who receive parenteral nutrition. The retained bile may lead to
gallbladder wall inflammation and ischemia, with subsequent microbial
invasion of the gallbladder mucosa. In immunocompetent patients, the
most common offending microorganisms include gram-negative bacilli and
anaerobes. In immunocompromised patients including patients with AIDS
(particularly in those who have not yet received benefit from highly active
antiretroviral therapy), organisms include CMV, Cryptosporidium spp.,
microsporidia, Isospora spp., Salmonella spp., and Campylobacter spp.
P.282
Clinical
Findings
and
mild
Treatment
Removal of the infected gallbladder and administration of antibiotics are
imperative. IV fluids and antibiotics should be started promptly.
Antibiotics should cover gram-negative bacilli and anaerobes (see
treatment of acute cholangitis).
ACUTE
CHOLANGITIS
Essentials
Fever,
Severe
of
jaundice,
Diagnosis
and
leukocytosis.
right-upper-quadrant
abdominal
pain.
More Common
Escherichia coli
Klebsiella
pneumoniae
Proteus mirabilis
Enterococcus
faecalis
Pseudomonas
aeruginosa
Enterobacteriaceae
Bacteroides
fragilis
Clostridium
perfringens
Escherichia coli
Klebsiella
pneumoniae
Pseudomonas
aeruginosa
Proteus mirabilis
Enterococcus
faecalis
Viridans
streptococci
Bacteroides
fragilis
Clostridium
perfringens
Less Common
Viridans
streptococci
Serratia spp.
Haemophilus
influenzae
Candida albicans
Cryptococcus
neoformans
Clonorchis
sinensis
Echinococcus
granulosus
Enterobacteriaceae
Serratia spp.
Morganella morgani
Aeromonas spp.
Pseudomonas
maltophila
Citrobacter
freundii
Peptostreptococci
Fusobacterium spp.
Children
Adults
General
Considerations
Clinical
abscess
formation.
Findings
Differential
Diagnosis
Complications
Prolonged, untreated obstructive jaundice may lead to hepatocellular
damage and possible cirrhosis. Hypoprothrombinemia may predispose the
patient to excessive bleeding. In contrast to hypoprothrombinemia in
hepatocellular disease, prolonged prothrombin times associated with
obstructive jaundice may be corrected with daily intake of vitamin K.
Treatment
Antibiotics and biliary drainage are the mainstays of treatment, because
acute cholangitis is invariably fatal without urgent decompression of the
biliary tree. Before drainage, IV fluid resuscitation and IV vitamin K (if
elevated prothrombin time) should be administered. The empiric antibiotic
regimen of choice should have broad-spectrum coverage of enteric gramnegative bacilli, however it is controversial whether gram-positive cocci
and anaerobes should be covered in the empiric regimen (Box 21-6 ). No
studies have shown a particular antibiotic regimen superior over others.
Combinations of antibiotics include a 7- to 10-day course of a -
Prognosis
With appropriate treatment, mortality from acute cholangitis is < 10%.
Mortality rates are higher in those with acute obstructive suppurative
cholangitis, sepsis, and severe underlying disease. Clinical factors
associated with poorer prognosis include old age, female sex, evidence of
acute renal failure, concomitant liver abscess or cirrhosis, and malignant
biliary
P.284
tract obstruction. Acidosis (pH < 7.4), hyperbilirubinemia (total bilirubin
> 90 mmol/L), hypoalbuminemia (albumin < 30 g/L), and
thrombocytopenia (platelet count < 150) also predicted poorer outcome.
First
Choice
Ampicillin/sulbactam
(300
mg/kg/d
IV
Allergic
Adults
RECURRENT
PYOGENIC
CHOLANGITIS
the biliary tree and allow for drainage. Treatment includes prompt
administration of broad-spectrum antibiotics and IV fluids. Drainage may
be needed in the 15% of cases that fail antibiotic therapy. Removal of
pigment stones and relieving biliary strictures may help prevent future
attacks.
SCLEROSING
CHOLANGITIS
toxic
AIDS-RELATED
CHOLANGITIS
REFERENCES
Infections Of The Liver
Cheney CP, Chopra S, Graham C: Hepatitis C. Infect Dis Clinics NA
2000;14:633 (Excellent comprehensive review of HCV.)
disease
processes.)
Schalm SW et al: Ribavirin enhances the efficacy but not the adverse
effects of interferon in chronic hepatitis C. Meta-analysis of individual
patient data from European centers. J Hepatol 1997;26:961 (This
meta-analysis of 186 patients showed that sustained normalization of
alanine aminotransferase and HCV RNA negativity was significantly
higher in IFN plus ribavirin combination therapy than either
monotherapy, without an increase in toxicity.)
Yu SC et al: Pyogenic liver abscess: treatment with needle aspiration.
Clin Radiol 1997;52:912 (Authors report their experience in the
aspiration of 101 liver abscesses and suggest this method may be as
safe and effective as continuous catheter drainage.)
prevention,
and
maintenance
therapy.)
2001
McGraw-Hill
&
Gynecologic
Infections
22
Obstetric &
Infections
Gynecologic
Yenjean S. Hwang MD
Merle A. Sande MD
GYNECOLOGIC
INFECTIONS
VULVOVAGINITIS
Essentials
of
Diagnosis
General
Considerations
periods).
- to +
- to +
Satellite
+
-
lesions
Consistency of discharge
Curdy
Frothy 25%
Homogenous, frothy sometimes
Color of discharge
White
Yellow-green,
Gray, white
Vaginal pH
4.5
4.7
4.7
Epithelial
25%
cells
Normal
Normal
Clue cells
PMNs per epithelial cells
Variable
>1
<1
Bacteria
Endogenous flora
Endogenous flora
Gram-variable
coccobacilli
Pathogens on microscopy
Yeasts and pseudohyphae, 50%
Trichomonads 70%
Gram-variable
coccobacilli
1 Source : Adapted from Rein MF: Vulvovaginitis and cervicitis. In
Mandell, Douglas, and Bennett's Principles and Practice of
Infectious
Candida
Table
More
Trichomonas
Bacterial
Vaginosis
Frequent
Gardnerella
vaginialis
Group A streptococci
Candida albicans
Candida
Trichomonas
vaginalis
Bacterial vaginosis (Gardnerella
Less
vaginalis )
Frequent
Haemophilus
influenzae
Enterobius
vermicularis
Staphylococcus
aureus
Herpes simplex virus
Human
papillomavirus
Mycobacterium
tuberculosis
Salmonellae
Enterobacteri-aceae
Actinomyces
Schistosomes
Children
Adults
Clinical
Findings (see Table 22-1,
Typical Features of Common
Vaginitides)
Differential
Diagnosis
Complications
Trichomonal infection can be complicated by vaginitis
emphysematosa, in which gas-filled pockets of tissue fill the
vaginal wall. This condition will resolve upon treatment of the
trichomonal infection. Women with trichomonal vaginitis are more
likely to have vaginal-cuff cellulitis after hysterectomy and, if
they are pregnant, are more likely to have premature or
prolonged rupture of membranes, premature labor, low-birthweight babies, and postabortion infection. Women with BV are at
increased risk for salpingitis, vaginal-cuff and wound infections
after surgery, postpartum fever, chorioamnionitis, premature
labor, and premature delivery. The treatment of both candidal
and trichomonal vaginitis may be complicated by frequent
recurrences.
Treatment
Vulvovaginal candidiasis is usually treated with topical antifungal
agents (Box 22-2 ). There are a wide variety of treatments, all of
which appear to be equally effective. Commercially available
preparations, usually imidazoles or triazoles, are safe in
pregnancy and tolerated well by patients. Treatment with an
imidazole for 7 days yields a cure rate of approximately
8094%. Shorter (3-day) regimens have approximately the
same cure rate with improved patient compliance. Single-dose
regimens do not appear to be as effective as the 3- or 7-day
treatments. Pregnant women may require longer treatment. Oral
therapy with fluconazole, ketoconazole, and itraconazole is
available as well, but the potential toxicities are greater, and
most patients do not require systemic therapy. Recurrent
infection can be a problem with vulvovaginal candidiasis and
probably results from endogenous relapse caused by small
numbers of yeasts that have survived treatment. The rate of
Prognosis
Topical treatment of candidal vulvovaginitis has a cure rate range
of 8094%. However, 36 weeks after completion of
treatment, Candida can be cultured from quite a few women
(933%) who have undergone this treatment. Subspeciation of
Candida suggests that approximately 40% of these women are
infected with new strains of Candida species. Our current
understanding of the mechanism of recurrence is extremely
limited. Therapy to decrease the number of recurrences is aimed
at eliminating or minimizing the aforementioned risk factors.
In Trichomonas
vaginalis infection, a single dose of metronidazole
reportedly provides a cure rate of 90%. For BV, cure rates
associated with treatment with metronidazole are reported to be
8090%.
CERVICITIS
Essentials
of
Diagnosis
General
Considerations
Choice
Choice
Trichomonas spp.
Bacterial
vaginosis
Frequent
trachomatis
N gonorrhoeae
Herpes simplex virus
Human
papillomavirus
Less
Frequent
Adenovirus
Measles virus
Cytomegalovirus
Enterobius
vermicularis
Amoebae
M tuberculosis
Group B streptococci
N meningitidis
BOX 22-3 Microbiology of Cervicitis
P.291
Clinical
Findings
distinguish
among
Laboratory
Findings. Gram stain of cervical discharge may
show numerous (1030) polymorphonuclear leukocytes per
oil immersion field. The presence of gram-negative diplococci
on the Gram stain confirms the diagnosis of N gonorrhoeae ,
but their absence does not rule out the possibility. Chlamydial
infection is suggested by the presence of intracytoplasmic
inclusions on Giemsa stain of cervical discharge. Fluorescent
antibody staining and enzyme-linked immunosorbent assays
(ELISA) to identify chlamydial antigens are also available, but
positive results need to be confirmed by culture. LCR or PCR
tests of cervical discharge or LCR tests of urine can help
make a rapid diagnosis of chlamydia or gonorrhea infection.
For both chlamydia and gonorrhea, culturing is also useful.
Differential
Diagnosis
Complications
Cervicitis caused by chlamydia or gonorrhea infection will
progress to PID in 1040% of women with cervicitis. Other
Treatment
Penicillinase-producing N gonorrhoeae species are becoming more
prevalent, making penicillin an ineffective choice for empiric
therapy of cervicitis. Current recommendations are in Box 22-4 .
The recommendations recognize that simultaneous infection with
C trachomatis and N gonorrhoeae is common, so that both
organisms should be treated. Pregnant women should not receive
tetracyclines. In addition, the newer macrolides have not been
approved for use in pregnant women.
Prognosis
As stated previously, 1040% of cervicitis cases caused by
gonococcal or chlamydial infection in women will progress to PID,
with the potential for infertility.
Prevention
&
Control
Choice
Choice
Allergic
Pregnant
Women
PELVIC
Essentials
INFLAMMATORY
of
DISEASE
Diagnosis
General
Considerations
Frequent
Neisseria
gonorrhoeae
Chlamydia
trachomatis
Bacteroides spp.
Peptostreptococcus
Enterobacteriaceae
Streptococci
Mycoplasma hominis and Ureaplasma
urealyticum
Garneralla
Less
vaginalis
Frequent
Clinical
Findings
for
Diagnosis above).
Laboratory
Findings. Findings on laboratory studies,
unfortunately, can be within normal limits. Abnormalities such
as a leukocytosis, elevated sedimentation rate, or C-reactive
protein can support the diagnosis, but their absence or
presence does not confirm the diagnosis. Gram stain of
cervical secretions may reveal the presence of gram-negative
diplococci,
suggesting N gonorrhoeae as the causative
organism. Culdocentesis may also be performed, and the fluid
obtained should be examined for white cells; the presence of
numerous white cells suggests PID, but appendicitis can also
present in the same manner.
Imaging. Ultrasonography of
inflammatory mass consistent
Laproscopy remains the most
PID and should be performed
remains uncertain. Hyperemia
Differential
Diagnosis
Complications
At least 25% of women with PID have serious sequelae, such as
infertility, ectopic pregnancy, and chronic pelvic pain. Acute
complications include pelvic peritonitis if there is rupture of an
abscess or extension of the infectious process into the peritoneal
space. Pelvic cellulitis with thrombophlebitis may result. Abscess,
bacteremia, and septic shock may develop.
Treatment
Treatment should begin with empiric antibiotics as soon as the
diagnosis is suspected. The CDC has published recommendations
transmitted
diseases.
Regimen A
Outpatient treatment: Doxycycline, 100 mg orally twice a day
14 days PLUS metronidazole, 500 mg orally twice a day
14 days
Inpatient treatment: Doxycycline, 100 mg IV or orally every
12 h PLUS one of the following:
Cefoxitin, 2.0 g IV every 8 h
Cefotetan, 2.0 g IV every 12 h
Inpatient treatment only recommended
erythromycin for doxycycline
Substitute
Regimen B
Outpatient treatment; Doxycycline, 100 mg orally twice a day
14 days PLUS one of the following:
Ceftriaxone, 250 mg IM once
Cefoxitin 2.0 g IM PLUS probenicid, 1 g orally once
Other parenteral third-generation cepha-losporin
(ceftizoxime or cefotaxime)
Substitute
Allergic
Pregnant
Women
Prognosis
A recent meta-analysis of 34 treatment regimens from 1966 to
1992 found cure rates to be above 90% for the commonly used
treatment regimens, which form the basis for the current CDC
treatment
guidelines.
Prevention
&
Control
INFECTIONS
SURGERY
Essentials
of
AFTER
GYNECOLOGIC
Diagnosis
General
Considerations
Frequent
Streptococci
Bacterioides
Prevotella
Gardnerella
Enterobacteriaceae
BOX 22-7 Microbiology of Gynecologic Postoperative
Infections
Clinical
Findings
Treatment
Patients with pelvic cellulitis can be treated with single-agent
antibiotic therapy. Cefotetan, cefoxitin, ampicillin/sulbactam, and
ticarcillin/clavulanic acid are all reasonable choices (Box 22-8 ).
In patients with -lactam allergies, clindamycin and gentamicin
can be used. Therapy should be continued until the
P.296
patient is afebrile for at least 24 hours, and administration of oral
antibiotics after parenteral treatment is generally thought to be
unnecessary.
First
Choice
Choice
Allergic
Pelvic
Abscess
Prevention
&
Control
INTRAPARTUM
INFECTIONS
&
POSTPARTUM
CHORIOAMNIONITIS
Essentials
of
Diagnosis
esterase
and
glucose
concentrations
General
Considerations
Clinical
Findings
More
Frequent
Enterobacteriaceae
Enterococci
Anaerobes
Streptococci
Less
Frequent
Gardnerella
vaginalis
Mycoplasma hominis
Herpes simplex virus
BOX 22-9 Microbiology of Chorioamnionitis
Complications
One complication of chorioamnionitis is dysfunctional labor,
necessitating induction or cesarean delivery. Approximately
three-quarters of women with chorioamnionitis require
augmentation of labor with oxytocin. Cesarean delivery is
required in approximately 40%. Left untreated, chorioamnionitis
can result in bacteremia in the mother and pneumonia and
bacteremia in the neonate.
Treatment
Antibiotics should be administered as soon as the diagnosis is
made (Box 22-10 ). Prompt delivery, usually within 12 hours, is
an essential part of treatment.
Prognosis
No maternal deaths from chorioamnionitis were reported in states
in which such statistics were tracked from the 1980s to early
1992. However, postpartum infection in the mother is very
common. Perinatal mortality is increased, with premature infants
at higher risk than term infants.
Prevention
&
Control
POSTPARTUM
ENDOMETRITIS
Essentials
of
Diagnosis
First
and
bacteremia
possible.
Choice
Choice
Allergic
General
Considerations
Chlamydia
trachomatis. Group A -hemolytic
cause endometritis as well, sometimes in
toxic shock. Nosocomial transmission and
and require special isolation procedures.
Ureaplasma
urealyticum and Mycoplasma hominis have also been
isolated from the endometrium and blood of affected patients.
Clinical
Findings
Differential
Diagnosis
Frequent
Group B streptococci
Enterococci
Aerobic
streptococci
Gardnerella
vaginalis
E coli
Prevoltella bivia
Bacteroides
Peptostreptococci
Streptococci
Staphylococci
Enterobacteriaceae
Anaerobes
Less
Frequent
Ureaplasma
urealyticum
Mycoplasma hominis
Chlamydia
trachomatis (in late endometritis)
Group A -hemolytic streptococci
Clostridium
perfringens
(myonecrosis)
Postpartum
Endometritis,
POVT
Episiotomy
Infection
Complications
Bacteremia can occur with postpartum endometritis and does
occur in 1020% of patients. However, it does not correlate
with severity of illness or with prolonged recovery.
First
Choice
2.0 g
1.7
million
nfection
Choice
Allergic
Puerperal Ovarian
Vein
Thrombophlebitis
Episiotomy
Infection
Treatment
Mild to moderately severe postpartum endometritis is treated
with an extended-spectrum penicillin (ticarcillin/clavulanic acid
or
In cases
infectious
have no
may be
pathogens.
Prognosis
The prognosis is usually good, because intravenous antibiotic
therapy is quite effective.
Prevention
&
Control
of
Diagnosis
General
Considerations
Clinical
Findings
Differential
Diagnosis
Complications
The complication of pulmonary embolization should always be
considered, especially if tachypnea, hypoxia, chest pain, or other
signs of respiratory distress develop.
Treatment
Continuous intravenous anticoagulation with heparin is important.
The optimal duration of anticoagulation is not known, but many
clinicians treat for 710 days (if pulmonary embolization has
not occurred). Administration of broad-spectrum antibiotics
against common pelvic pathogens is also helpful (Box 22-12 ).
P.301
Prognosis,
Prevention,
&
Control
EPISIOTOMY
Essentials
of
INFECTIONS
Diagnosis
General
Considerations
Clinical
Findings
Complications
Sepsis as well as pelvic abscess and extensive necrosis of pelvic
structures may occur if early infections are not diagnosed and
treated
promptly.
Treatment
Simple infections may be treated with an oral antibiotic such as
amoxicillin/clavulanic acid. Optimal therapy for more serious
infections involves both systemic antibiotics and surgical
dbridement (Box 22-12 ).
Prognosis
For simple episiotomy infections, the prognosis is quite good,
with few complications seen. More serious infection such as
myonecrosis can have a graver prognosis.
SEPTIC
Essentials
ABORTION
of
Diagnosis
General
Considerations
Clinical
Findings
shock.
Differential
Diagnosis
Frequent
Bacteroides
Group A and B streptococci
Enterobacteriaceae
Chlamydia
trachomatis
Less
Frequent
Clostridium
perfringens
Complications
Postabortion infection can progress to bacteremia and frank
shock. Perforation of the uterus may occur both during abortion
and during curettage. Pelvic or adnexal abscesses may result
from untreated infection. Necrotizing myometritis with
Clostridium spp. can also occur.
Treatment
Simple postabortion endometritis requires only oral doxycycline
(Box 22-14 ). More serious infections require curettage and
parenteral antibiotic therapy. Laproscopy or laporotomy and
hysterectomy may be necessary when the condition fails to
respond to curettage and appropriate antibiotics.
Prognosis
The prognosis is generally good for simple postabortion
endometritis. Patients in whom therapy fails have a high risk of
infertility owing to the necessity of hysterectomy, whereas
patients with C perfringens infection may have a grave prognosis.
Prevention
&
Control
INFECTIONS OF SPECIAL
DURING
PREGNANCY
GROUP
Essentials
STREPTOCOCCUS
of
CONCERN
(GBS)
Diagnosis
General
Considerations
Choice
Choice
Allergic
Clinical
Findings
Treatment
Treatment of GBS infection in the mother and neonate includes
empiric broad-spectrum antibiotics until culture results are
known. Penicillin is the antibiotic of choice, once cultures are
confirmed.
Prevention
&
Control
Choice
Choice
Allergic
OTHER
SYPHILIS
Esentials
IN
of
PREGNANCY
Diagnosis
General
Considerations
or
Syphilis
Positive RPR or VDRL confirmed by FTA-ABS
Positive IgM, positive PCR on amniotic fluid
Almost 100% if mother has primary or secondary syphilis; 80% in
early latent syphilis
Stillbirth, late abortion; hepatosplenomegaly, deafness, jaudice,
interstital keratitis, congenital stigmata
Toxoplasmosis
Serology (IgG, IgM)
Elevated IgM, consistent clinical presentation, positive PCR on
amniotic fluid
Maternal
Diagnosis
Table
Fetal
Diagnosis
Risk of
Transmission
Congenital/Fetal
Effects
very likely
that
quite
is an 80%
Clinical
Findings
investigation
None
Vaccination of all women of child-bearing age
VZV
Acyclovir, 10 mg/kg every 8 h IV or 800 orally 5 times per
day; VZIg, if given, should be given within 96 h of exposure
Acyclovir, 10 mg/kg every 8 h
Avoid exposure of nonimmune pregnant women to chickenpox
or zoster
HSV
Acyclovir, 200 mg orally 5 times per day for 710 days for
primary infection; 200 mg orally 5 times per day for 5 days
for recurrences
Acyclovir, 10 mg/kg IV every 8 h
Cesarean delivery if active lesions
Treatment of
Mother
Treatment of
Neonate
Prevention &
Control
Differential
Diagnosis
Treatment
The treatment of a pregnant woman with syphilis is the same as
that in the general population. Some clinicians recommend that
penicillin-allergic pregnant patients be desensitized to penicillin,
as penicillin is thought to be the only antibiotic that reliably
treats the fetus as well as the mother. Some practitioners
recommend a second dose of benzathine penicillin G 1 week after
the initial dose, especially in the third trimester. After treatment,
the woman should be monitored with quantitative serologic titers
and re-treated if there is a fourfold or higher increase in the
titer.
Prognosis,
Prevention,
&
Control
TOXOPLASMOSIS
Essentials
of
IN
PREGNANCY
Diagnosis
or
General
Considerations
Clinical
Findings
Differential
Diagnosis
Treatment
Many practitioners consider documentation of first-trimester fetal
infection a reason for termination of pregnancy. Maternal
infection between conception and the 24th week of gestation may
also justify termination of the pregnancy.
When maternal infection is confirmed, treatment with spiramycin
(1.5 g twice a day orally) should be started and continued
throughout the pregnancy. Such treatment has been reported to
reduce the incidence of fetal infection by 60%. Toxicity is
minimal, and although generally available in Europe, spiramycin
can be obtained in the United States only by application to the
U.S. Food and Drug Administration (FDA). Pyrimethamine and
sulfadiazine also can reduce the rate of transmission to the fetus
and prevent progressive fetopathy but are associated with more
toxicity. Folinic acid, 6 mg orally 3 times a week, should be given
with this regimen. Because of the potential for teratogenicity,
some clinicians recommend that pyrimethamine be begun only
after the 14th week of gestation.
In the neonate, treatment of overt toxoplasmosis involves 6
months of therapy with pyrimethamine plus sulfadiazine and
folinic acid and an additional 6 months of alternating monthly
therapy with spiramycin. Healthy infants suspected of having
congenital infection can be treated with pyrimethamine and
sulfadiazine for 21 days followed by spiramycin until a definitive
diagnosis is established.
Prognosis
The prognosis is good for the mother; 15% of infants born to
infected mothers will be severely affected.
Prevention
&
Control
CYTOMEGALOVIRUS
Essentials
of
IN
PREGNANCY
Diagnosis
General
Considerations
Clinical
Findings
Treatment
There is no approved treatment available for congenital infection.
Viruria can be suppressed with adenine arabinoside, but rebounds
as soon as therapy is stopped. Ganciclovir therapy is being
studied in research protocols.
Prognosis
As stated earlier, neurologic deficits will develop in 1020% of
asymptomatic infants within the first 2 years of life. Of infants
infected in utero, cytomegalic inclusion disease will develop in
between 6% and 19%, with a mortality rate approaching 30%.
Prevention
&
Control
RUBELLA
IN
PREGNANCY
Essentials
of
Diagnosis
lymphadenopathy,
and
General
Considerations
Clinical
Findings
Treatment
There is no treatment for infected infants or mothers, other than
supportive care.
Prognosis
Prevention
&
Control
VARICELLA INFECTION
PREGNANCY
Essentials
of
DURING
Diagnosis
General
infection
diagnosed
serologically.
Considerations
Clinical
Findings
Prognosis
Although the actual rate of fetal transmission is unknown,
Treatment
&
Prevention
HERPES SIMPLEX
IN PREGNANCY
Essentials
Characteristic
of
VIRUS
INFECTIONS
Diagnosis
lesions
in
mothers.
encephalitis,
and
General
Considerations
Clinical
Findings
Treatment
&
Prevention
The mother may be treated with oral acyclovir if she has active
Prognosis
It has been estimated that for a woman experiencing a primary
episode of genital herpes at the time of delivery, there is a 50%
risk of her neonate acquiring neonatal herpes, whereas for a
woman who has a recurrence of genital herpes at the time of
delivery, the risk is 3%.
HUMAN PAPILLOMAVIRUS
PREGNANCY
Essentials
Condylomata
of
IN
Diagnosis
acuminata
in
mothers.
General
Considerations
Clinical
Findings
Treatment
Lesions are treated if they cause discomfort or when it is
anticipated that they will interfere with delivery. Trichloroacetic
acid (50% or 80%) in 70% ethanol applied to the lesions three
times a week or once a week is inexpensive and safe for the
mother and fetus. Cryotherapy and laser ablation are also safe
and well-tolerated in pregnant women. Podophyllin, 5-fluorouracil
cream, and interferon therapy should not be administered to
pregnant
women.
Prognosis,
Prevention,
&
Control
REFERENCES
Vulvovaginitis
Hiller SL et al: Role of bacterial vaginosis-associated
microorganisms in endometritis. Am J Obstet Gynecol
1996;175:435.
Cervicitis
Centers for Disease Control and Prevention: Guidelines for
treatment of sexually transmitted diseases. MMWR
1998;47(No.
RR-1).
Lee RV: Sexually transmitted diseases. In Burrow GN, Ferris
TF (editors): Medical Complications during Pregnancy.
Saunders, 1995.
Rein MF: Vulvovaginitis and cervicitis. In Mandell GL, Bennett
JE, Dolin R (editors): Mandell, Douglas and Bennett's
Principles and Practice of Infectious Diseases. Churchill
Livingstone,
1995.
Pelvic
Inflammatory
Disease
Infections
After
Gynecologic
Surgery
hysterectomy.
Obstet
Gynecol
1991;77:450.
Chorioamnionitis
Gibbs RS, Duff P: Progress in pathogenesis and management
of clinical intra-amniotic infection. Am J Obstet Gynecol
1991;164:1317.
Postpartum
Endometritis
endometritis.
Obstet
Gynecol
1986;
68:226.
Puerperal Ovarian
Thrombophlebitis
Vein
(POVT)
Episiotomy
Infections
Septic
Abortion
Group
Streptococcus
(GBS)
Syphilis
in
Pregnancy
Toxoplasmosis
in
Pregnancy
on
Cytomegalovirus
in
Pregnancy
Varicella
Infection
During
Pregnancy
Herpes Simplex
Pregnancy
Virus
Infections
In
Human
Papillomavirus
In
Pregnancy
General
Burrow GN et al (editors): Medical
Pregnancy. Saunders, 1995.
Complications
during
Obstetrics. Appleton
2001
McGraw-Hill
23
Patients with Aids
Dani-Margot
Zavasky
MD
Essentials
of
Diagnosis
General
Considerations
Central/Eastern
transmitted diseases
part of the world.
by the end of
antiretroviral
prophylaxis
with
zidovudine
(AZT).
PREDICTORS OF
PROGRESSION
DISEASE
CD4 Lymphocyte
Monitor)
Count
(Immunologic
CD4 lymphocytes are the major cellular target for HIV. Both
absolute CD4 counts and the rate of decline have prognostic
predictive value and are used to determine the need for
antiretroviral therapy and for opportunistic infection
prophylaxis. CD4 counts do not accurately indicate viral load per
se, but they predict the short-term risks for progression to
AIDS-related
illness.
CLINICAL
SYNDROMES
1.
CONSTITUTIONAL
SYMPTOMS
Mental
Status
Encephalopathy
Thrombocytopenia
Lymphopenia, then atypical
Transaminitis
High-level HIV viremia
lymphocytosis
meningitis
(HIV)
Headache
Photophobia
Fever
CSF: lymphocytic pleocytosis; mild, modest increase in
protein
Immune
Easy
Thrombocytopenic
Purpura
(ITP)
bruising
Epistaxis
Splenomegely
Thrombocytopenia; no evidence of production defect on
bone
marrow
aspiration
Have benefitted from antiretrovirals, especially AZT +/prednisone. Options for refractory cases: IVIG, Danazol, alphainterferon,
splenectomy
Midstage Disease (CD4 200-500) Mycobacterium tuberculosis
(TB)
Classic reactivation pulmonary disease with higher CD4 counts;
cough, fever, weight loss, upper lobes infiltrate, pulmonary
cavities. Atypical presentation with lower CD4 with hilar
adenopathy, diffuse pulmonary infiltrates without cavitation,
pleural effusions, or extrapulmonary disease (blood, lymph
nodes, CNS, genitourinary tract, pleura).
CXR; sputum: AFB smear and culture; bronchoscopy if sputum
is negative; blood cultures for AFB positive in 40%; pleural or
lymph node biopsy
Sarcoma
(HHV-S)
recommended;
bronchoscopy
or
visceral
disease
cough,
visualized
bronchospasm.
during
endoscopy.
Disease
(Streptococcus
pneumoniae )
Pneumococcal
patients.
Thrush
(oral
vaccine
recommended
for
all
HIV-positive
Candidiasis)
Syndrome
& Cause
BOX
23-1
Clinical
Presentation
Laboratory
Correlates
Treatment
and
Prophylaxis
Infections,
Headache
Headache may pose a challenging diagnostic dilemma. Besides a
vast array of opportunistic CNS infections and malignancies, it
can result from muscle tension, or a systemic illness without a
direct affliction of intracranial structures. Headache can be
induced by a medication frequently used for treatment of HIV
disease, for example, AZT, or by migraine not related to HIV
infection. At any stage of the HIV disease, patients are more
susceptible to bacterial meningitis or sinusitis as well as to
neurosyphilis. Other opportunistic infections tend to occur at
specific levels of immunosuppression.
Early Disease (CD4 > 500). Aseptic meningitis probably
caused by HIV itself can accompany acute seroconversion in
the early stage of HIV disease.
3.
GASTROINTESTINAL
SYMPTOMS
Dysphagia
Swallowing difficulty (dysphagia) is frequently accompanied by
pain (odynophagia). Patients complain about the sensation of
food sticking. Appropriate diagnosis and treatment are
important not only to alleviate the discomfort but also to
prevent weight loss and malnutrition. At any stage of HIV
disease, patients can develop reflux esophagitis. However,
esophageal complaints and disorders are more typical for late to
advanced disease.
Midstage Disease (CD4 200500). Early thrush (oral
mucosal candidiasis) can occur with some esophageal
discomfort. In that setting, PCP prophylaxis is indicated
irrespective of the CD4 count.
Late Disease (CD4 75200). Most common cause is
Candida esophageal mucosal infection with frequent
concomitant oral lesions. HSV type 1 or 2 can induce
mucosal ulceration.
Advanced Disease (CD4 < 75). Same as late disease, but
CMV and aphthous ulcers are more frequently encountered.
Diarrhea
Diarrhea is a commonly encountered clinical problem in HIVinfected patients and may be caused by HIV itself. Symptoms
range from frequent loose stools to fulminant diarrhea,
producing profound weight loss, malabsorption, and
intravascular fluid depletion. A thorough evaluation is warranted
because virtually any gastrointestinal pathogen may be found.
Both small bowel and colon can be affected, causing enteritis or
colitis, respectively. Symptoms of enteritis include profuse,
watery diarrhea often with symptoms of bloating, nausea, and
periumbilical cramping. Volume depletion and malabsorption
may be marked. Colitis presents with fever, lower abdominal
pain, tenesmus, and passage of frequent, small volume stools
with mucus and sometimes blood. Characteristics of symptoms
can guide the choice of initial diagnostic procedure but are
unreliable to predict the most likely pathogen. CD4 cell count
can, again, be useful in outlining differential diagnosis.
At any CD4 cell count, the following agents should be
considered: Clostridium difficile; Salmonella, Campylobacter,
Shigella , and Cyclospora spp.; Entamoeba histolytica; Giardia
lamblia; Isospora belli; enteroviruses; and Strongyloides
stercoralis. Most of the antiretroviral drugs also cause diarrhea.
Late Disease (CD4 75200). Cryptosporidium
parvum
and Microsporidium spp. should also be considered in
addition to those listed above.
Advanced Disease (CD4 < 75). Mycobacterium
avium
complex and CMV should be included in the differential
diagnosis.
4. RESPIRATORY SYMPTOMS
(DYSPNEA/COUGH)
The differential diagnosis of lower respiratory symptoms is
immitis,
Cryptococcus
neoformans , or
Histoplasma
capsulatum are also possible. Kaposi's sarcoma
is also known to cause pulmonary lesions, especially with
worsening
immunodeficiency.
Advanced Disease (CD4 < 75). Besides the above
etiologies, Pseudomonas
aeuruginosa and Aspergillus
species can be encountered, especially with neutropenia or
repeated hospital exposure. Non-Hodgkin's lymphoma can
also affect lungs. Isolation of CMV and Mycobacterium
avium
complex is common, but they rarely cause symptomatic
pulmonary disease.
5.
CUTANEOUS
LESIONS
Disease
(CD4
200500).
Mucocutaneous
signifying
profound
immunosuppression.
Treatment
In the past 2 years, tremendous progress has been made in
treatment of HIV infection. New combination treatment
regimens can suppress virus replication below the level of
detection in many individuals. However, cure is still not
possible.
Antiretroviral treatment guidelines are undergoing rapid
evolution, but some consensus about general principles has
been achieved. First, the major goal of treatment is to suppress
viremia and prevent immunosuppression. To reduce the risk
of
immunosuppression.
long-term
treatment
toxicity.
Primary
Table
Purpose(s)
Sensitivity
Specificity
Detection/measurement of HIV
A. HIV-1 p24 antigen (Assumes acid pretreatment to
dissociate immune complexes)
Diagnosis of acute HIV syndrome (antibody not detectable
for 2 months)
Used to screen all donated blood
% positive depends on method/ stage of disease, eg, in acute
retroviral syn.: 100%; if CD4 200500, 4570%; if CD4 <
200, 75100%
B. Measurement of plasma viral burdens Due to
assay differences, use same assay repeatedly for a given
patient. REsults with RT-PCR consistently 2-fold or more greater
than bDNA
For given assay, need change of 0.5 log 10 for significant
change
Current methods:
(1) Couples reverse transcription (RT) to a DNA PCR
amplification (RT-PCR) (Roche)
NOTE: Ideally collect with EDTA & separate plasma within 6 hrs.
>98
(2) Amplification of RNA of HIV; a nucleic acid sequencebased
amplification (NASBA) (Organon Teknika)
>98
(3) Identification of HIVRNA then signal amplification by DNA
branched-chain
technique (referred to as bDNA) (ChironBayer)
>98
Test
Table
Current Use
% Positive
fatigue,
anemia,
neturopenia,
Epivir
150 mg twice daily
Generally well tolerated; active against HBV
AZT + 3TC
Combivir
1 tablet twice daily
Combination tablet containing 300 mg of AZT and 150 mg of
3TC
Didanosine (ddl)
Videx
200 mg twice daily or 400 mg once daily on empty stomach
(>60 kg body weight) or 250 mg (orally, each day) (<60 kg
body weight)
Clinical data supports twice-daily dosing as more effective.
Peripheral neuropathy in 15%, pancreatitis; avoid alcohol.
Contains antacid: ok to give tablets at same time as all NRTIs,
nevirapine and efavirenz; delavirdine and indinavir must be
taken at least 1 h prior to ddl: nelfinavir can be taken 1 h after
ddl
Zalcitabine (ddC)
Hivid
0.3750.75 mg 3 times daily
Peripheral neuropathy in 1731% of trial participants; oral
ulcers
Stavudine (d4T)
Zerit
40 mg twice daily (>60 kg body weight) 30 mg bid (for <60 kg)
Peripheral neuropathy (14% in early studies; 24% in
expanded access patients with CD4+ counts <50)
Abacavir (ABC)
Ziagen
300 mg twice daily
About 3%5% hypersensitivity
reaction:
fever,
malaise,
Generic
Brand
Dose
Comments and
Common Side
Effects
Table
Efavirenz
Indinavir ritonavir1
Ritonavir2 + saquinavir
Nevirapine
Stavudine + lamivudine
Stavudine + didanosine
Zidovudine + lamivudine
Zidovudine + didanosine
Abacavir
Amprenavir
Delavirdine
Lopinavir/ritonavir
(Kaletra)
Nelfinavir + saquinavir
Ritonavir
Saquinavir SGC3
Didanosine + lamivudine
1
Column B
Alternative
Column A
Column B
P.324
P.325
P.326
Numerous clinical trials confirmed that antiretroviral
combination therapy results in greater reductions of viral RNA
copies, less frequent emergence of resistance, and a more
sustained therapeutic response. Available data and clinical
experience support using a combination of two NRTIs along with
a PI as the most potent combination available (HAART).
However, the choice of drugs has to be individualized based not
only on the patient's virologic and immunologic response but
also on the patient's tolerance of side effects, ease of use,
potential drug-drug interactions, and cost. With growing
numbers of new antiretrovirals, the recommendations about the
best combination therapy continue to be modified. Alternatives
to the two NRTI-one PI combination are indicated in Table 23-5
).
For suggestions when initial treatment fails, See Table 23-6 .
Responses to failure.
Medical care should focus on providing comfort, preventing the
opportunistic infections, and managing the new complexities of
antiretroviral therapy. In the terminal stage of HIV disease,
treatment of the virus itself along with opportunistic infections
and especially the malignancies is often palliative and should be
instituted after careful consideration of the potential
complications of therapy. A thorough discussion of these facts
with the patients will facilitate realistic treatment expectations.
The use of life-support measures, including cardiopulmonary
resuscitation and mechanical ventilation, should also be
addressed as early as possible. The survival rate for AIDS
patients with respiratory failure has actually improved in the
past few years, and intensive care is certainly not
contraindicated. However, the expected benefit from aggressive
measures must be balanced against the overall quality of life in
the face of progressive disease.
Prognosis
Throughout the course of HIV disease, there is an active viral
replication and concomitant stimulation and destruction of the
immune system, even during the clinically asymptomatic period.
The rate of progression of the infection that eventually
culminates in complete destruction of the CD4 lymphocytes is
determined by a balance between the pathogen virulence
factors and the host genetic make-up and immune defenses
against HIV.
Prevention
&
Control
prevention
counseling
and
postexposure
REFERENCES
Carpenter CJ et al: Antiretroviral therapy for HIV infection in
1997. JAMA 1997;277:1962.
Centers for Disease Control: Update: trends in AIDS
incidenceUnited States, 1996. MMWR 1997;46:861.
De Roda Husman AM et al: Association between CCR5
genotype and the clinical course of HIV-1 infection. Ann
Intern Med 1997;127:882.
Karon JM et al: Prevalence of HIV infection in the United
States,
19841992.
JAMA
1996;276:126.
1998;279:35.
World Health Organization: HIV/AIDS. The global epidemic.
Wkly Epidemiol Rec 1997;72:17.
2001
McGraw-Hill
24
Infections in
Recipients
Transplant
Robin Patel MD
Essentials
of
Diagnosis
features
include
the
following:
history
(type,
dose,
duration).
(travel,
tuberculosis,
animals,
occupation,
etc).
General
Considerations
transplantation
involves
harvesting
PBSC
or
may be warranted.
Pretransplantation
Infectious
Diseases
Evaluation
Before transplantation, all potential candidates should be
evaluated for active infection that may require therapy or
preclude transplantation, risk factors for infection, including
latent infections that might be reactivated post-transplantation,
and the use of immunosuppressive agents. A complete history
should be obtained, focusing on any history of infection and any
unusual exposures (Table 24-1 ). A complete physical
examination should also be performed. Table 24-1 outlines
infectious disease tests that should be performed
pretransplantation.
Further investigations are pursued depending on elicited risks.
For example, serologic testing for Coccidioides
immitis may be
performed on a patient with a history of travel to or residence
in the southwestern United States or Mexico. Patients who have
traveled to or resided in an area where Strongyloides
stercoralis
is endemic should be examined for evidence of infection with
this parasite. Lung transplant candidates should be evaluated
for colonization of the respiratory tract with such agents as
Aspergillus spp.
Timing
of
Infection
Post-Transplantation
Solid-Organ
Transplantation. There are three time
frames, influenced by surgical factors, the level of
immunosuppression, and environmental exposures, during
which infections of specific types
P.329
most frequently occur after solid-organ transplantation (Box
24-1 ). These include the first month; the second through
the sixth months; and the late post-transplant period
(beyond 6 mo).
History
Immunosuppressive therapy:
or past)
Antibiotic
allergies
type
and
duration
(current
History
gardening
Drinking water source
Exposure to young children
Dietary habits: consumption of raw meat and seafood
and unpasteurized milk products
Complete Review of Systems
Complete Physical Examination
Laboratory
Testing
Pretransplantation:
Tuberculin skin test
Chest and sinus x-ray
Urinalysis and urine culture for bacteria
Serologic tests: cytomegalovirus, varicella zoster virus,
Epstein-Barr virus, herpes simplex virus,* Toxoplasma
gondii,* * syphilis,
hepatitis A virus, hepatitis B virus, hepatitis C virus,
HIV, (coccidioides
immitis if history of exposure
presentsee
text)
Post-transplantation:
Cultures and stains for bacteria, viruses, fungi,
mycobacteria, etc, as indicated
Serologic testing as indicated
**Heart transplant
*Optional
Table
candidate
2-6
post-transplant
Cytomegalovirus
Pneumocystis
carinii
Aspergillus spp.
Nocardia spp.
Toxoplasma gondii
Listeria
monocytogenes
Mycobacterium
tuberculosis
Histoplasma
capsulatum
Coccidioides
immitis
From 6 months onward post-transplant
Respiratory
viruses
Urinary tract infection
Streptococcus
pneumoniae
Varicella zoster virus (reactivation)
Cytomegalovirus
(retinitis)
Nontuberculous
Anytime
mycobacteria
post-transplant
Cryptococcus
neoformans
Hepatitis B or C
Human
immunodeficiency
virus
disease)
Cytomegalovirus
Aspergillus spp.
Bacteria
Adenovirus
RSV
Parainfluenza
BK virus
virus
BACTERIAL
COMMON
INFECTIONS
BACTERIAL
INFECTIONS
Prevention
Selective bowel decontamination reduces
infections in liver transplant recipients.
gram-negative
Prevention
The incidence of bacterial pneumonia in lung
recipients may be dramatically reduced by the
antimicrobial agents tailored to the results of
stains for bacteria and fungi from the airways
recipient at the time of transplantation.
transplant
use of
cultures and
of the donor and
Prevention
Prophylaxis with trimethoprim-sulfamethoxazole reduces the
incidence of bacterial infection of the urinary tract and
bacteremia after renal transplantation. However, controversy
exists regarding the exact dosing, timing, and duration of
trimethoprim-sulfamethoxazole for urinary tract infection
prophylaxis in renal transplant recipients.
E. Pancreas and Small Bowel Transplant Recipients.
The most common bacterial infections in pancreas transplant
recipients are wound and intra-abdominal infections (see
Chapters 12 and 1 3 ). Human small bowel transplant
recipients are likewise at risk for intra-abdominal and wound
infections.
F. PBSC and Bone Marrow Transplant Recipients. Since
the early 1980s, the bacterial causes of infection in patients
Prevention
Bacterial infections in PBSC and bone marrow transplant
patients with graft-versus-host disease after engraftment may
be prevented by prophylaxis with trimethoprimsulfamethoxazole. Oral chemophylaxis with quinolones in
granulocytic patients is widely used. Oral quinolones are well
tolerated and eliminate most gram-negative bacterial infections.
The use of quinolones for prophylaxis is, however, controversial.
LEGIONELLA
General
SPECIES
Considerations
Clinical
Findings
Treatment
Treatment is classically with a quinolone or macrolide with or
without rifampin (Box 24-2 ). If legionellal pneumonia is
nosocomial, a search should be made for sources of legionella in
the environment, especially in the hot water supply and
ventilation
systems.
NOCARDIA
General
SPECIES
Considerations
Clinical
Findings
Treatment
Sulfonamides, either alone or in combination with trimethoprim,
are the treatment of choice for nocardiosis (Box 24-2 ).
Alternatives include minocycline, chloramphenicol,
erythromycin,
amikacin,
ampicillin,
amoxicillin-clavulanate,
ciprofloxacin, imipenem, meropenem, ceftriaxone, cefuroxime,
and cefotaxime, but antibiotic susceptibility testing should be
performed because resistance may be present. Antimicrobial
therapy should be continued for a prolonged period after cure
because of the tendency for relapse, although the optimal
duration of therapy is unknown.
Prevention
Trimethoprim-sulfamethoxazole
used
for P carinii
may prevent nocardiosis (Box 24-3 ).
prophylaxis
SALMONELLA SPP.
There is an increased incidence of salmonellal infection in renal
transplant recipients. The most common presentation is a febrile
illness with bacteremia. Salmonella infections are discussed
further in Chapter 53 .
LISTERIA
General
MONOCYTOGENES
Considerations
bacteria
monocytogenes
simplex
virus
mucocutaneous
disease
zoster
virus
carinii
Trimethoprim-sulfamethoxazole
in divided doses) or
(15-20
mg/kg/d
IV
or
orally
stercoralis
(200
g/kg/d)
gondii
Clinical
Findings
Prophylactic
Measures
Vaccinations
(administered
prior
to
solid-organ
transplantation)
prophylaxis
simplex
virus
stomatitis
prophylaxis
zoster
virus
prophylaxis
carinii
prophylaxis
or
gondii
prophylaxis
for P carini
recipients)
Quinolone
(various
regimens)
tuberculosis
infection
prophylaxis
Precautions
of
epidemiologic
exposures
post-transplantation
See text
Mycobacterium
Airborne
tuberculosis
isolation
infection
precautions
Treatment
Intravenous ampicillin and gentamicin are recommended for
treatment (Box 24-2 ). Trimethoprim-sulfamethoxazole is also
effective.
Prevention
Trimethoprim-sulfamethoxazole,
used
for P carinii
may additionally prevent listeriosis (Box 24-3 ).
VIRAL
prophylaxis,
INFECTIONS
CYTOMEGALOVIRUS
General
Considerations
transplant
recipients
(controversial).
Clinical
Findings
Treatment
Effective currently available antiviral agents for the treatment of
CMV include ganciclovir, foscarnet, cidofovir, and intravenous
immune globulin (Box 24-2 ). In solid-organ transplant
recipients, intravenous ganciclovir is the mainstay of therapy.
Ganciclovir alone is generally of little benefit for treatment of
either CMV pneumonia or gastroenteritis in PBSC and bone
marrow transplant recipients, although the combination of
intravenous ganciclovir plus intravenous immune globulin
appears to have some efficacy. The absorption of ganciclovir
after oral administration is low, and its use cannot be
recommended for the treatment of CMV infection and disease
after
transplantation.
Prevention
Selection of Organs from CMV Seronegative Donors for
CMV Seronegative Recipients. Knowledge of the CMV
serostatus of the donor and recipient
P.338
pretransplant will predict which patients will develop CMV
disease. Although the solid-organ transplant patient at
highest risk for development of CMV infection is the
seronegative recipient of a seropositive allograft, protective
matching of seronegative donors and recipients is not
currently advocated (Box 24-3 ).
Use of CMV Seronegative, Filtered, or Leukocyte-Poor
Blood Products. The use of CMV seronegative, filtered, or
leukocyte poor blood products reduces CMV transmission,
and these should be used at least in seronegative recipients.
Active Immunization with a Vaccine. In theory, one of
the simplest interventions for the prevention of CMV disease
after transplantation would be immunization of seronegative
recipients with a vaccine given once in anticipation of future
viral challenge. A live attenuated CMV vaccine, which uses
clinical
trials.
HERPES
General
SIMPLEX
VIRUS
Considerations
Clinical
Findings
Treatment
Treatment of HSV infection is with acyclovir (Box 24-2 ). Side
effects of acyclovir include local inflammation or phlebitis after
intravenous infusion, renal toxicity caused by precipitation and
crystallization of the drug in the renal tubules, confusion,
delirium, lethargy, tremors, seizures, nausea, light-headedness,
diaphoresis, and rash. Mucocutaneous infection in transplant
recipients should be treated with oral acyclovir if the infection
has a benign course or with intravenous acyclovir in more
serious cases. Disseminated or deep HSV infection should
always be treated with intravenous acyclovir.
Newer agents, such as famciclovir and valacyclovir, may be
used instead of acyclovir. Although more toxic than acyclovir,
ganciclovir and foscarnet are also effective against HSV. A
concern with respect to chronic acyclovir use is the development
of acyclovir resistant mutants of HSV. Acyclovir resistance may
arise from mutations in the genes for thymidine kinase or DNA
polymerase. Acyclovir resistance has been associated with
progressive and severe disease in immunocompromised
patients, particularly in those with HIV, and it is possible that
resistance will become a problem for transplant recipients in
years ahead.
Prevention
Low-dose acyclovir prevents HSV stomatitis in transplant
recipients
(Box 24-3 ).
VARICELLA
General
ZOSTER
VIRUS
Considerations
Clinical
Findings
Treatment
For localized dermatomal zoster, the recommended treatment is
intravenous acyclovir (Box 24-2 ). Oral famciclovir, valacyclovir,
or acyclovir may be used as an alternative. For primary VZV
infection, treatment consists of intravenous acyclovir in addition
to varicella zoster immune globulin.
Prevention
Because of the high mortality rate associated with primary VZV
infection in transplant recipients, all candidates should be
screened for antibody to VZV pretransplantation (see Box 24-3
). Seronegative individuals should be urged to report promptly
all exposures to VZV and varicella zoster immune globulin
should be administered within 96 hours of exposure.
Intravenous acyclovir should be administered within 24 hours of
eruption of a skin rash if one occurs. Unfortunately, progression
to severe disease and death can still occur. The use of low-dose
acyclovir as HSV prophylaxis probably prevents VZV reactivation
and possibly primary infection, although this has not been
formally studied. Despite concerns regarding the use of live
vaccines in transplant recipients, a recent study has
demonstrated the safety of the VZV vaccine in pediatric renal
transplant recipients. This vaccine should preferably be
administered several months prior to solid-organ transplant,
should reduce morbidity in seronegative solid-organ transplant
recipients, and should provide considerable cost savings.
Uncomplicated
post-transplantation
infectious
mononucleosis
Fever, pharyngitis, cervical adenopathy, {+/-} splenomegaly
Acyclovir
Good
Benign polyclonal polymorphic
Fever, pharyngitis, cervical adenopathy,
Acyclovir,
ganciclovir,
(+/-)
immunosuppression
Good
B-cell hyperplasia
Early malignant transformation in polyclonal polymorphic B-cell
lymphoma
Fever,
(+/-)
pharyngitis,
adenotherapy
chemotherapy,
radiation
therapy,
Poor
1 Adapted, with permission, from Hanto DW: Classification of
Epstein-Barr
virus-associated
post-transplant
lymphoproliferative diseases: implications for understanding
their pathogenesis and developing rational treatment strategies.
Annu Rev Med 1995; 46: 381.
2 IFN, interferon.
Conditions
Table
Clinical
Findings
Treatment
Outcome
EPSTEIN
BARR
VIRUS
General
Considerations
organs.
provided
in Chapter 33 .
Clinical
Findings
Treatment
Treatment of EBV-related PTLD is outlined in Table 24-2 . Highlevel EBV oropharyngeal shedding found in primary infection is
inhibited by acyclovir and ganciclovir, suggesting that antiviral
therapy may be useful early when levels of viral replication are
low. Unfortunately, once PTLD is established, treatment has
been disappointing with the exception of drastically reducing the
level of immunosuppression, which appears to have a beneficial
effect in localized or polyclonal as well as multifocal or
monoclonal PTLD. Disease localized to the transplanted organ or
lymph nodes can be reversed with reduced immunosuppression
and antiviral therapy; extranodal, multifocal, and brain disease
typically require chemotherapy, radiation therapy, or both and
are associated with a high mortality rate.
OTHER
General
VIRUSES
Considerations
malignancies
FUNGAL
(Chapter 45 ).
INFECTIONS
PNEUMOCYSTIS
General
CARINII
Considerations
Clinical
Findings
Treatment
P carinii pneumonia is treated with high doses of trimethoprimsulfamethoxazole or intravenous pentamidine (Box 24-2 ). The
former regimen is preferable.
Prevention
Trimethoprim-sulfamethoxazole
provides
excellent
prophylaxis
for P carinii pneumonia and should be given to all transplant
recipients following transplantation (Box 24-3 ). Prolonged
prophylaxis is indicated for heart-lung and lung transplant
recipients and for patients with ongoing risk factors for P carinii
pneumonia such as multiple episodes of rejection, ongoing
graft-versus-host disease, treatment with antilymphocyte
therapy, or persistent allograft dysfunction. Importantly,
prophylaxis should be reinstituted if it has been discontinued, in
patients receiving augmented immunosuppression. Alternatives
to trimethoprim-sulfamethoxazole for prophylaxis include
intravenous or aerosolized pentamidine, dapsone, and
atovaquone. For single lung allograft recipients who cannot
tolerate trimethoprim-sulfamethoxazole, there is some
controversy about the use of aerosolized pentamidine that may
be inadequately
P.342
delivered to the remaining diseased and therefore poorly
ventilated lung.
CANDIDA
General
SPECIES
Considerations
Clinical
Findings
Treatment
Agents used for the treatment of serious candidal infections in
transplant recipients include amphotericin B, fluconazole,
Prevention
The use of a selective bowel decontamination regimen may
reduce the incidence of candidal infections in liver transplant
recipients. Fluconazole has been shown to prevent both deep
and superficial candidal infections, excluding those caused by C
krusei , in liver and PBSC and bone marrow transplant
recipients (Box 24-3 ).
CRYPTOCOCCUS
General
NEOFORMANS
Considerations
Clinical
Findings
with C
MYCELIAL
General
FUNGI
Considerations
see Chapter 70 .
Clinical
Findings
Treatment
Treatment of deep fungal infections in transplant recipients does
not differ significantly from that in other types of
immunocompromised hosts (Box 24-2 ). Immunosuppression
should be reduced as tolerated. Surgical extirpation or
debridement should be performed for diagnostic and therapeutic
purposes, if appropriate. Intravenous amphotericin B has been
the mainstay of treatment for deep fungal infections in
transplant recipients. The combination of cyclosporin and
amphotericin B has been associated with renal failure. Some
organisms (eg P boydii ) are resistant to amphotericin B,
emphasizing the need for identification of all fungal isolates in
transplant recipients. Lipid formulations of amphotericin B have
fewer side effects, especially including nephrotoxicity, than the
standard preparation, but are more costly. Because of the high
frequency of toxicity seen with amphotericin B, the use of azole
antifungal agents for treating select fungal infections in
Prevention
Laminar air flow isolation in PBSC and bone marrow transplant
units prevents aspergillal infections. Intravenous amphotericin B
should be given to PBSC and bone marrow transplant recipients
with a well-documented history of invasive aspergillosis
pretransplant.
MYCOBACTERIAL
MYCOBACTERIUM
General
INFECTIONS
TUBERCULOSIS
Considerations
Clinical
Findings
P.344
Treatment
See Chapter 61 .
Prevention
A detailed history of tuberculosis exposure should be obtained
on all transplant candidates and a tuberculin test should be
performed on all solid-organ transplant candidates and on PBSC
and bone marrow transplant candidates with a history of
tuberculosis exposure. Isoniazid prophylaxis is recommended for
patients with positive tuberculin tests or other risk factors for
tuberculosis. If possible isoniazid prophylaxis should be
administered for nine months pretransplantation. If this is not
feasible, isoniazid can be given following transplantation. In
addition, tuberculin test positive transplant recipients who have
not previously received treatment or prophylaxis might benefit
from isoniazid prophylaxis when they receive antilymphocyte
preparations.
NONTUBERCULOUS
General
MYCOBACTERIA
Considerations
PARASITIC
INFECTIONS
TRYPANOSOMA
General
CRUZI
Considerations
TOXOPLASMA
General
GONDII
Considerations
Clinical
Findings
Treatment
Toxoplasmosis is treated with pyrimethamine with folinic acid
and either sulfadiazine or clindamycin (Box 24-2 ).
Prevention
Toxoplasmosis is generally prevented by the same doses of
trimethoprim-sulfamethoxazole
used
for P carinii prophylaxis
(Box 24-3 ). An alternative is pyrimethamine.
STRONGYLOIDES
General
STERCORALIS
Considerations
Clinical
Findings
Treatment
Thiabendazole or ivermectin is used to treat strongyloidiasis
(Box 24-2 ).
Prevention
As noted in the discussion on the pretransplantation evaluation,
patients who have traveled to or resided in an area of endemic
infection should be examined for evidence of infection with this
parasite
pretransplantation.
Differential
Recipients
Diagnosis
in
Transplant
Prevention of
Recipients
Infections
in
Transplant
(Box
24-3 ).
Avoidance of Epidemiologic Exposures Posttransplantation. After transplantation, patients should be
again counseled regarding measures aimed at reducing
infections. Patients who are not immune to VZV should be
counseled to avoid exposure to persons with chickenpox or
shingles. If such an exposure does occur, a physician should
be contacted immediately. All fresh fruits and vegetables
should be washed. All meat and seafood should be cooked
thoroughly. The source of the patient's drinking water
should be reviewed. Patients with cats should avoid
changing litter boxes if possible. (If changing the litter box
is unavoidable, gloves should be worn and the litter box
REFERENCES
Basgoz N, Preiksaitis JK: Post-transplant lymphoproliferative
disorder. Infect Dis Clin N Am 1995;9:901.
Guidelines for preventing opportunistic infections among
hematopoietic stem cell transplant recipients. MMWR. Oct
20, 2000, Vol. 49, No. RR-10.
Hanto DW: Classification of Epstein-Barr virus-associated
post-transplant lymphoproliferative diseases: implications for
understanding their pathogenesis and developing rational
treatment strategies. Annu Rev Med 1995;46:381.
P.346
Hibberd PL, Rubin RH: Clinical aspects of fungal infection in
2001
McGraw-Hill
25
Patients with Neutropenia &
Fever
David Dockrell MD
Linda L. Lewis MD
Essentials
of
Diagnosis
General
Considerations
including
infections
Gram-Positive
Bacteria
S aureus
Coagulase-negative
staphylococci
Enterococci
Viridans
streptococci
Corynebacterium
jeikeium
Bacillus spp.
Clostridium spp.
Gram-Negative
Bacteria
E coli
K pneumoniae
P aeruginosa
Enterobacter spp.
Acinetobacter spp.
Stenotrophomonas
maltophilia
Citrobacter
freundii
Serratia
marcescens
Legionella spp.
Mycobacteria
M
M
fortuitum
cheloneae
Fungi
C albicans
C kruzei
C tropicalis
T glabrata
Aspergillus spp.
Mucor
Rhizopus
Fusarium
Trichosporon
Pseudoallescheria
boydii
Cryptococcus
Malassezia furfur
Viruses
Herpes simplex virus
Varicella-zoster
virus
Cytomegalovirus
Parasites
Pneumocystis
carinii
Toxoplasma gondii
Strongyloides
stercoralis
Type of Organism
More
Frequent
Less
Frequent
Clinical
Findings
occasionally
Examination:
Skin rashes
Ecthyma
gangrenosum
Black eschar
Inspection of all intravascular devices
Lesions may suggest bacteremia or candidemia
Consider P aeruginosa but rarely E coli or Candida spp .
Fungi, especially Aspergillus or Mucor
Potential site of infection (inspect in particular for tunnel or
exit-site infections); bacteria include coagulase-negative
staphylococci, S aureus , occasional gram-negative bacteria,
fungi (Candida spp., often non-albicans )
Mouth examination
interstitial
infiltrate
transplant
fungal
infection
recipient
likely
Hepatosplenic
candidiasis
Wide range of potential pathogens (see Chapter 24 )
Assessment
Table
Comments
P.350
Laboratory
Findings. At least two blood cultures should be
performed initially. If an indwelling venous catheter is in
place, blood for cultures should be obtained through the
if
bronchoalveolar
lavage
is
nondiagnostic.
Differential
Diagnosis
Figure
Figure
Complications
Superinfection is a recognized complication of febrile neutropenia
in patients receiving antimicrobial agents. It is usually defined as
the development of documented infection during or < 1 week
after the discontinuation of antimicrobial therapy. Superinfection
occurs in 20% of cancer patients with neutropenic fever.
Fungi account for 2567% of superinfections. Risk factors for
superinfection
include
P.352
a longer duration of profound neutropenia (< 100
neutrophils/mm3 ), persistence of fever after 3 days of therapy,
and presence of a central venous catheter.
Treatment
The initiation of empirical antibiotic therapy for any febrile
neutropenic patient with a single oral temperature elevation >
38.5C or three or more oral temperatures recorded at >
38.0C within 24 h has become the standard of care. Even
though many patients have no demonstrable infection, it is
assumed that most have occult infection. The rapidity with which
these patients' clinical status can deteriorate during infectious
episodes and the demonstration that empirical therapy decreases
mortality have supported the use of empirical therapy for
neutropenic fever.
The selection of empirical therapy should be influenced by the
epidemiological and pathogenic concerns mentioned. Its design
should consider the predominant microorganisms encountered at
a given center, their expected susceptibility patterns, and the
clinical features and laboratory test results.
First Line
Ceftazidime, 2 g (50 mg/kg)1 every 8 h IV, plus
tobramycin/gentamicin, 2.0 mg/kg load then 1.7 mg/kg (2.0
Allergy
Initial
Regimen
Modification of
Regimen After 3
Days of Persistent
Fever
Modification of
Regimen After 57
Days of Persistent
Fever
regimens.
of
Prognosis
The outcome of neutropenic fever can be defined in terms of
microbiologic response and clinical outcome and is related to
recovery from neutropenia. Among patients with documented
bacterial infections, treatment with ceftazidime or cefepime
monotherapy,
cephalosporin-aminoglycoside
combinations,
piperacillin-tazobactam, or carbapenem monotherapy have been
associated with microbiologic cure rates > 90%. Fungal
microbiological response rates are much lower.
Clinical response rates are often defined in terms of resolution of
fever after 4 days of treatment, need to alter initial empirical
antimicrobial agents, and survival. Overall -lactam
monotherapy has been associated with resolution of fever after 4
days of therapy in ~ 60%, need for subsequent antimicrobialagent modification in ~ 60%, and overall survival of 9098%.
The mortality rate associated with documented bacterial causes
of neutropenic fever has fallen from 90% in the 1950s to <10%
in the 1990s.
Prevention
&
Control
REFERENCES
Freifeld A et al: A double-blind comparison of empirical oral
and intravenous antibiotic therapy for low-risk febrile patients
with neutropenia during cancer chemotherapy. N Engl J Med
1999;341:305.
Hathorn JW, Lyke K: Empirical treatment of febrile
neutropenia: evolution of current therapeutic approaches.
Clin Infect Dis 1997;24:(Suppl 2)S256.
Hughes WT, et al: 1997 guidelines for the use of antimicrobial
agents in neutropenic patients with unexplained fever. Clin
Infect Dis 1997;25:551.
Lee JW, Pizzo PA: Management of the cancer patient with
fever and prolonged neutropenia. Hematol Oncol Clin North
Am 1993;7:937.
2001
McGraw-Hill
26
Patients with Recurrent
Infections and Leukocyte
Abnormalities
Timothy R. La Pine MD
Harry R. Hill MD
A critical and delicate balance in both cellular and humoral
function is essential for complete immunologic responsiveness
to invasive microbial pathogens. Any alteration in immune
regulation or responsiveness may render a host susceptible to
recurrent or life-threatening infections. Understanding the
specific functional mechanisms involved in leukocyte production,
activation, migration, and immune regulation leading to cytoxic
killing is of extreme clinical significance when evaluating
patients with suspected immunodeficiency.
Leukocyte abnormalities should be suspected in the following
patients: (1) those who have an increased frequency of
infections compared to patients of similar age and exposure
risks; (2) those whose infections with common, often
nonpathogenic or usually inconsequential pathogens are more
severe than would normally be expected; (3) those whose
T-LYMPHOCYTE
Essentials
of
DEFECTS
Diagnosis
disease
low
after
absolute
blood
transfusions.
lymphocyte
counts.
Hypocalcemia/tetany
with
Intracellular infections
viruses, or fungi).
General
DiGeorge
(caused
by
facies.
bacteria,
protozoans,
Considerations
T-LymphocyteMediated Defects
Severe combined
immunodeficiency
DiGeorge syndrome
Wiskott-Aldrich
syndrome
Ataxia
telangiectasia
B-Lymphocyte
Abnormalities
Bruton's
agammaglobulinemia
Hyper IgM syndrome
Selective IgA deficiency
Common variable
immunodeficiency
Phagocytic
Cell
Defects
Leukocyte
adhesion
deficiency
Jobs syndrome
Chronic
granulomatous
disease
Chediak-Higashi
Complement
Defects
syndrome
Deficiency of C1 and C4
C2 deficiency
C3 deficiency
Deficiency of C5, 6, 7, 8,
9
Properdin
deficiency
as a T-cell
and release a
of events that
response with the
cell types. IL-2 also
Table
Antibody
Deficiency
Cell-Mediated
Immunodeficiency
T-cell function
Tests for HIV antibodies and
viral load if suspected
Complement
Deficiency
Phagocyte
Defect
1 PPD,
Table
Antibody
Deficiency
Cell-Mediated
Immunodeficiency
etc)
Measure T-cell proliferation
with mitogens, antigens, and
allogeneic cells (MLR) and
lymphokine
production
Enzyme assays for ADA or PNP
deficiency
Complement
Deficiency
Specific component
determinations
Phagocyte
Leukocyte adhesive
glycoprotein
analysis
(CD11a/CD18,
CD11b/CD18,
Defect
T-Cell
Deficiencies
B-Cell
Deficiencies
Phagocytic
Leukocyte
infusions
Cell
Defects
G-CSF
Future gene replacement
therapies are being explored
Gamma interferon for CGD
patients may be beneficial in Job
patients
Prophylactic antibiotic therapy as
indicated
Complement
Defects
Methyltestosterone derivatives
C1 esterase deficiency
Prophylactic antibiotic therapy
indicated
in
as
Meningococcal
vaccine
Pneumoccal vaccine
P.359
SEVERE
COMBINED
IMMUNODEFICIENCY
Clinical
Findings
unresponsiveness.
receptor
signal
-chain
mutation.
transduction
defects.
histocompatibility
complex
class
II
deficiency.
Diagnosis
Prenatal diagnosis of SCID may be made by fetal blood sampling
of T-lymphocyte subsets and T-cell functional studies as early as
20 weeks gestation.
Treatment
The only curative therapy for SCID is allogeneic bone marrow
transplantation, although the use of cytokines, particularly
recombinant human IL-2, may be of value for SCID patients who
fail to produce IL-2.
1.
X-LINKED
SCID
2.
ADENOSINE
DEAMINASE
DEFICIENCY
Clinical
Findings
Diagnosis
Treatment
Bone marrow transplantation or enzyme replacement with
bovine ADA has been used with some success in the
management of this disease. Promising recent attempts to treat
patients with ADA deficiency have used autologous lymphocytes
or cord blood stem cells corrected in vitro with retroviral vectorinserted normal human ADA DNA.
3.
ZAP-70
Clinical
DEFICIENCY
Findings
Diagnosis
The diagnosis of this disease is suggested by family history,
symptoms of SCID, and the characteristic peripheral T-cell
phenotype and function.
Treatment
At present, bone marrow transplantation is the only curative
therapy.
4.
PURINE-NUCLEOSIDE
PHOSPHORYLASE
DEFICIENCY
Clinical
Findings
Diagnosis
The diagnosis can be made by measuring PNP in hemolyzed
erythrocytes. Heterozygotes have half the normal level of this
enzyme and associated serum uric acid levels are low in these
patients. Prenatal diagnosis is possible by assaying PNP levels
cultured in amniotic cells during the second trimester.
Treatment
DIGEORGE
Clinical
SYNDROME
Findings
Diagnosis
Prenatal diagnosis of DiGeorge syndrome can be performed by
fluorescence in situ hybridization of fetal tissue to look for the
chromosomal monosomy at 22q-11.
Treatment
Treatment of patients with DiGeorge syndrome has included the
implantation of fetal thymic tissue, fetal thymic epithelium, or
fetal thymus in a diffusion chamber, all of which have
demonstrated limited success. Bone marrow transplantation,
which provides donor postthymic T cells to reconstitute the
patient's immunity, has been successfully used to treat patients
with DiGeorge syndrome.
WISKOTT-ALDRICH
Clinical
SYNDROME
Findings
Laboratory
Findings. Wiskott-Aldrich syndrome patients
have low serum concentrations of IgM. IgA and IgE
concentrations are high, and the IgG level is normal,
elevated, or only slightly depressed. These patients are
unable to produce antibody in response to polysaccharide
antigens. T-cell numbers and function progressively
decrease in this disorder, leading to a profound leukopenia.
Patients have increased susceptibility to autoimmunity and
malignancy.
Diagnosis
Prenatal diagnosis is facilitated by fetal blood sampling and the
analysis of thrombocyte numbers and size, as well as an
analysis of the pattern of X chromosome inactivation to detect
carriers.
Treatment
Bone marrow transplantation, or more recently stem cell
transplantation, may correct the immunologic defects and
platelet disorder observed in these patients.
ATAXIA-TELANGIECTASIA
Clinical
Findings
of cytotoxic T cells.
Diagnosis
Serum -fetoprotein levels are persistently elevated in these
patients, which may be a useful but nonspecific aid in the
diagnosis.
Treatment
Therapy consists of intravenous immunoglobulin therapy using
IgA-depleted preparations. Gene therapy for ataxia
telangiectasia is currently under investigation.
B-LYMPHOCYTE
Essentials
of
DEFECTS
Diagnosis
gastrointestinal
and/or
sinopulmonary
infections.
General
lymphoid
hyperplasia
and
malignancies.
Considerations
produce
B-cell
immunodeficiency
syndromes.
BRUTON'S
Clinical
AGAMMAGLOBULINEMIA
Findings
Diagnosis
Female carriers do not exhibit antibody deficiency and can be
detected by analyzing the unbalanced pattern of X chromosome
inactivation in peripheral blood mononuclear cells. Prenatal
diagnosis of suspected patients is facilitated by sex
determination of the fetus and direct sampling of fetal blood for
mature B cells or by DNA markers.
Treatment
Therapy (Box 26-2) consists of the administration of
intravenous immunoglobulin and clinical surveillance for
infections and the development of lymphoreticular and other
malignancies.
X-LINKED
HYPOGAMMAGLOBULINEMIA
WITH
NORMAL TO INCREASED IgM
CONCENTRATIONS
Clinical
Findings
autosomal recessive fashion. The underlying cause of the Xlinked hyper-IgM syndrome is a deficiency in the expression of
the T-cell CD40 ligand, which specifically binds B cells and
drives the immunoglobulin isotype switch. The gene for the
CD40 ligand has been cloned and mapped to Xq-26.
Signs and Symptoms. Neutropenia is commonly associated
with this disease, and nearly half of these patients have
hepatosplenomegaly. Chronic liver disease and lymphomas
are the long-term associated consequences of this disorder.
Laboratory
Findings. These patients have normal or
increased concentrations of serum IgM and, in some cases,
IgD but decreased or absent IgG, IgA, and IgE. T-cell
numbers and function, other than the absence of the CD40
ligand, appear to be normal. The interaction of CD40 with
its ligand, however, may also be involved in early thymic Tcell maturation. This may explain an increased susceptibility
to opportunistic infections such as Pneumocystis
carinii
pneumonia seen in some patients.
Diagnosis
Prenatal diagnosis can be performed by DNA analysis and from
cytometry for the CD40 ligand on T cells.
Treatment
Bone marrow transplantation has recently been tried in the
treatment of hyper-IgM syndrome. Stem cell transplantation has
also been attempted. Replacement therapy with a recombinant,
soluble form of the CD40 ligand or gene therapy may be
developed for these patients in the future.
P.363
SELECTIVE
IgA
DEFICIENCY
Clinical
Findings
variable immunodeficiency,
disorders. The cause of
a terminal block in B-cell
of secreting the IgA
Diagnosis
Selective IgA deficiency has been defined as a serum IgA
concentration of < 5 mg/dL in severe deficiency and less than
two standard deviations below the mean of age-matched control
in partial deficiency. In some IgA deficient patients, secretory
IgA is low but present; the serum concentration of IgA may
return to normal within 4 years of diagnosis. These patients
have normal T-cell immunity.
Treatment
Therapy with IgA is not possible in patients with selective IgA
deficiency because (1) the half-life of IgA is short (~7 days),
(2) administered IgA is not transported to the mucosal surfaces,
and (3) the presence of anti-IgA autoantibodies in IgA-deficient
patients may cause anaphylactic reactions when blood
components containing IgA are transfused. In ~20% of the IgAdeficient patients who have frequent infections, there is an
associated
IgG-2
subclass
deficiency.
COMMON
VARIABLE
IMMUNODEFICIENCY
Clinical
Findings
are
additional
features
Laboratory
Findings. Common variable immunodeficiency
is characterized by markedly decreased serum
immunoglobulin levels, normal or nearly normal numbers of
circulating immunoglobulin-bearing mature B cells, impaired
antibody responses, and recurrent bacterial sinopulmonary
infections associated with chronic progressive
bronchiectasis.
Diagnosis
Assessing a male patient with recurrent infections and
significant hypogammaglobulinemia, the absence of mature
immunoglobulin B cells in the peripheral blood or X chromosome
inactivation analysis of the patient's mother can be helpful in
distinguishing sporadic cases of X-linked agammaglobulinemia
from cases of CVID.
Treatment
Management of CVID includes immunoglobulin replacement
therapy, antimicrobial therapy and pulmonary drainage, and
immunomodulatory therapies including recombinant human
conjugated with polyethylene glycol and cimetidine.
IL-2
of
Diagnosis
cellulitis,
and
P.364
and
Granulomatous
General
lymphadenitis.
lesion.
Considerations
LEUKOCYTE
Clinical
ADHESION
DEFICIENCY
Findings
that
facilitates
neutrophil
polarization,
Diagnosis
The diagnosis can be made by assessing the expression of
CD11b or CD18 on the patient's neutrophils by flow cytometry.
Further confirmation can be made by assessing expression of
these glycoproteins after exposure to a degranulating stimuli.
The expression of these glycoproteins is increased 5- to 20-fold
after stimulation with degranulating agents. This method is also
helpful for identification of symptom-free heterozygotes where
the expression of these glycoproteins is about half that seen in
normal carriers and for prenatal diagnosis.
Treatment
Therapy consists mainly of early, aggressive antibiotic therapy
to reduce bacterial infections (see Box 26-2). During severe
infections, granulocyte transfusions in addition to antibiotic
therapy have had therapeutic benefit. Bone marrow
transplantation has been successfully used to treat some
patients. Gene therapy, replacing the defective CD18 gene in
the patient's myeloid precursor cells, may become available in
the future. In vitro correction of CD18-deficient lymphocytes by
retrovirus-mediated gene transfer has been accomplished. A
transfection efficiency of 510% may be sufficient to change
the disease course from severe to moderate.
P.365
JOB'S
SYNDROME
Clinical
Findings
Diagnosis
Differentiation of patients with the Job syndrome from those
with atopic dermatitis is sometimes difficult and is dependent on
the presence of recurrent deep abscesses along with the classic
facial features.
Treatment
Management consists of controlling the pruritic eczematoid
dermatitis with emollient creams, topical steroids, and
antihistamines. Prophylactic oral dicloxacillin or trimethoprimsulfamethoxazole
for S aureus infections or oral fluconazole for
preventing C albicans infections usually benefit patients.
Intravenous immunoglobulin therapy should be reserved for
patients with confirmed IgG subclass deficiency, a finding rarely
observed in our experience. Plasmapheresis has been attempted
for a few patients who do not respond to more conservative
therapies. Reported experimental immunomodulatory therapies
include the use of levamisole, ascorbic acid, cimetidine, and
transfer factor. -Interferon therapy has been shown to
increase these patient's neutrophil chemotactic response in vitro
and decrease eczema and respiratory secretions in vivo.
CHRONIC
Clinical
GRANULOMATOUS
DISEASE
Findings
Diagnosis
The diagnosis of CGD is demonstrated by an absent or greatly
diminished respiratory burst by stimulated phagocytes.
Available assays include nitroblue tetrazolium dye reduction,
chemiluminescence, measurement of oxygen consumption, and
the products of oxidative metabolism, superoxide anion, and
hydrogen peroxide. A documented inability of blood
granulocytes to kill ingested catalase-positive bacteria confirms
CGD. Symptom-free carriers of the X-linked form of CGD can be
identified by determining the respiratory burst activity of their
neutrophils, which is approximately half of normal, and by
genetic analysis.
Prenatal diagnosis can be made during the second trimester by
sampling of fetal blood and nitroblue tetrazolium testing, which
serves as a screen for superoxide
P.366
production. Molecular reagents prepared from cloned DNA may
also prove to be clinically useful for prenatal diagnosis in the
future.
Figure
Treatment
Prophylaxis with trimethoprim-sulfamethoxazole may prolong
infection-free intervals by preventing infections, especially with
staphylococci. Therapy also includes treatment with interferon, which has decreased infections by as much as 70%,
and bone marrow transplantation, which to date has shown only
limited success and should be reserved for those patients who
cannot be optimally treated in other ways. Patients with CGD
are excellent candidates for future gene therapy because the
genetic lesions have been identified and the genes cloned.
CHEDIAK-HIGASHI
SYNDROME
Clinical
Findings
Diagnosis
The diagnosis is made by identification of the characteristic
giant cytoplasmic granules in the patient's leukocytes or
microscopic examination of hair shafts for abnormal giant
melanosomes. Prenatal diagnosis is possible by measuring the
large acid phosphatase-positive lysosomes in cultured amniotic
fluid cells, chorionic villus cells, or fetal blood leukocytes.
Treatment
In addition to prophylaxis with antibiotics and the prompt
treatment of acute infection with antimicrobial agents, high
doses of ascorbate may be beneficial. Bone marrow
transplantation may be curative.
P.367
Splenectomy has been used in the treatment of patients
unresponsive to other forms of therapy and has resulted in
clinical,
hematologic,
and
immunologic
improvement.
of
Diagnosis
Recurrent
infections
Recurrent
sepsis
with
encapsulated
bacteria.
General
Considerations
DEFICIENCY
OF
C2
DEFICIENCY
OF
C3
DEFICIENCY
OF
C5-C9
PROPERDIN
DEFICIENCY
REFERENCES
Ammann AJ et al: Antibody (B-cell) Immunodeficiency
Disorders in Medical Immunology, 9th ed. Appleton & Lange,
1997.
Arrufo A et al: The CD-40 ligand, gp 39, is defective in
activated T cells from patients with X-linked hyper IgM
syndrome. Cell 1993;72:291.
Bordignon C et al: Gene therapy in peripheral blood
lymphocytes and bone marrow for ADA immunodeficient
patients. Science 1995;270:470.
Castigli E et al: Severe combined immunodeficiency with
selective T-cell cytokine genes. Pediatr Res 1993;33:52.
P.369
Christenson JC et al: Infections complicating congenital
manifestations
1997;278:1835.
and
in
Sullivan KE et al: A multi institutional survey of the WiskottAldrich syndrome. J Pediatr 1994;125:876.
Taylor AMR et al: Fifth international workshop on ataxiatelangiectasia.
Cancer
Res
1993;53:138.
Clinical
2001
McGraw-Hill
27
Enteroviruses
W. Lawrence Drew MD, PhD
Essentials
of
Diagnosis
General
Considerations
a single strand of
It encodes a
to produce the
virus. In addition to
P.372
CLINICAL
SYNDROMES
POLIOVIRUS
INFECTION
occur.
Clinical
Findings
infections
are
asymptomatic.
Pediatric
Adult
More
Common
Febrile rash
Meningitis
Meningitis
Less
Common
Hand-footmouth
Pleurodynia
Myopericarditis
Herpangina
syndrome
Neonatal
sepsis
COXSACKIEVIRUS
INFECTIONS
&
ECHOVIRUS
1.
HERPANGINA
Clinical
Findings
2.
PLEURODYNIA
Clinical
(BORNHOLM
DISEASE)
Findings
3.
MENINGITIS
Clinical
Findings
4.
ENTEROVIRAL
Clinical
EXANTHEMS
Findings
5.
HAND-FOOT-AND-MOUTH
Clinical
DISEASE
Findings
6.
ACUTE
Clinical
BENIGN
PERICARDITIS
Findings
7.
MYOCARDITIS
Clinical
Findings
Findings.
Electrocardiographic
changes
are
8.
OTHER
SYNDROMES
Diagnosis
Poliovirus. Poliovirus grows well in monkey kidney tissue
culture, and the virus may be isolated from the pharynx during
the first few days of illness and from the feces for 30
days. The CSF is rarely positive for the virus, although a
pleocytosis of 25300 leukocytes usually occurs. Neutrophils
may predominate early, especially in aseptic meningitis. Protein
and glucose levels in CSF are usually normal or only slightly
Treatment
No specific antiviral therapy is approved for enterovirus
infections, but pleconaril, a drug active against picornaviruses
in vitro, is being evaluated for the treatment of enteroviral
meningitis and viremia. Immune globulin has been used in
immunocompromised patients with chronic enteroviral infection
of the central nervous system (Box 27-2) and can diminish viral
titers in body fluids.
Prevention
&
Control
First
Choice
Pediatric
Considerations
See above
Prophylactic
Measures
Isolation
Careful
handwashing
Precautions
contact
Stool precautions
after
patient
REFERENCES
Expanded Program on Immunization, Pan American Health
Organization: Certification of poliomyelitis eradication in the
Americas. Morbid Mortal Weekly Rep 1994; 43:720.
2001
McGraw-Hill
28
Rhinoviruses
W. Lawrence Drew MD, PhD
Essentials
of
Diagnosis
General
Considerations
infections.
RHINOVIRUS
Clinical
INFECTION
Findings
Children
More
Common
Less
Upper respiratory
infection
Adults
Upper respiratory
infection
Common
First
Choice
Second
Choice
Pediatric
Considerations
Treatment
No specific antiviral Rx
Prognosis
Because rhinovirus illnesses are usually uncomplicated, the
prognosis for recovery is excellent, but as mentioned above in
the complications section, exacerbations of chronic lung disease
may occur, and fatal illnesses in immunocompromised patients
have been reported.
Prevention
&
Control
Prophylactic
Measures
Isolation
Precautions
P.379
The multiple serotypes and apparent antigenic drift in rhinovirus
antigens suggest that successful vaccines are unlikely.
Formalin-inactivated, parenterally administered vaccines induce
antibody in serum but not in nasal secretions and are not as
useful as those given intranasally.
Prophylactic topical interferon is effective but associated with
unacceptable side effects. Since transmission is person to
person, infection may be reduced by minimizing finger to nose
and hand to hand spread as well as by covering coughs and
sneezes.
REFERENCES
Colonno RJ: Virus receptors: The Achilles' heel of human
rhinovirus. Adv Exp Med Biol 1992;312:61.
Gwaltney JM Jr: Combined antiviral and antimediator
treatment of rhinovirus colds. J Infect Dis 1992;166:776.
Smith TJ et al: Structure of human rhinovirus complexed
with Fab fragments from a neutralizing antibody. J Virol
1993;67:1148.
2001
McGraw-Hill
29
Influenza
Lisa Danzig MD
Keiji Fukuda MD, MPH
Essentials
of
Diagnosis
General
Considerations
below).
INFLUENZA
Clinical
INFECTION
Findings
Laboratory
Findings. Results of routine laboratory tests
are not specific for influenza. Leukocyte counts are variable.
Severe leukopenia has been described in overwhelming
illness. Leukocytosis of > 15,000 cells/mL should raise the
suspicion of a secondary bacterial process. Specific
laboratory tests to confirm influenza include viral culture,
rapid antigen detection, and serology.
Virus can be isolated from nasal washing and
nasopharyngeal swab specimens obtained within 34 days
of illness. Virus is grown either in embryonated hens' eggs
or in primary tissue culture systems, such as Madin-Darby
canine kidney cells. Viral culture offers specific information
and the ability to further characterize the isolate, but the
sensitivity of this technique is highly dependent on the
timing of when the specimen is obtained. Results usually are
not available for at least 3 days.
Rapid diagnostic techniques to identify viral antigens in
clinical specimens include immunofluorescence, enzyme
immunoassay, and time-resolved fluoroimmunoassay.
Several rapid test kits are now commercially available that
either can 1) detect influenza A but not influenza B virus; 2)
detect influenza A or B virus but not distinguish between
them; or 3) detect influenza A or B virus and distinguish
between them. In general, these tests are more specific
than sensitive but head-to-head comparison data are not
available. These tests can yield results within 30 min.
Reverse transcriptase polymerase chain reaction assays
have also been used to detect influenza virus RNA in clinical
specimens.
Serologic techniques for measuring antibody against
influenza include hemagglutination inhibition, neutralization,
enzyme immunoassay, and complement fixation. In general,
serology is a sensitive technique for establishing influenza
infections. However, serologic tests usually require acute
and convalescent serum samples to demonstrate a
significant increase in antibody level. The measurement of
More
Frequent
Frequent
Gastrointestinal
Persistent fatigue
a
Adultsa
BOX 29-1
Influenza
Differential
Other
respiratory
Diagnosis
viruses,
including
respiratory
syncytial
virus,
Complications
The most common serious complications of influenza include
exacerbation of underlying chronic pulmonary and
cardiopulmonary diseases, such as worsening of chronic
obstructive pulmonary disease, asthma, and congestive heart
failure, as well the development of pneumonia. Secondary
bacterial pneumonias occur much more frequently than primary
viral pneumonia and usually are associated with Streptococcus
pneumoniae, Staphylococcus aureus , and Haemophilus
influenzae. With complicating bacterial pneumonia, the patient
typically reports a period of improvement followed by the
appearance of signs and symptoms suggestive of pneumonia,
such as pleuritic chest pain, productive cough, and fever. On
chest radiography, lobar consolidation can be seen and sputum
smears show polymorphonuclear leukocytes with bacteria.
Primary viral pneumonia is an infrequent but often fatal
complication in which influenza progresses within the first
2448 h of illness and leads to increasing dyspnea,
tachypnea, and cyanosis. On presentation, fever and cough are
usually present and the patient appears uncomfortable and
dyspneic. On chest auscultation, diffuse fine rales with wheezes
or coarse breath sounds may be evident. Sputum may be scanty
but can be blood streaked. Chest roentgenograms usually show
unclear.
Treatment
Uncomplicated cases of influenza are usually treated
symptomatically. Salicylates should be avoided in children < 18
years of age because of the risk of Reye's syndrome. There are
two classes of licensed antiviral agents, the adamantines and
the neuraminadase inhibitors, with specific activity against
influenza viruses. The adamantines, amantadine hydrochloride
and rimantadine hydrochloride, have specific activity against
influenza A virus but not B virus. The neuraminadase inhibitor
drugs, zanamivir and oseltamivir, have activity against both
influenza A and B viruses. Amantadine is licensed for use in
children and adults, whereas rimantadine is licensed for use in
adults. Both drugs can be given for treatment of or prophylaxis
against influenza A virus but are ineffective against influenza B
virus. These chemically related drugs are equally effective and
appear to inhibit viral replication by blocking the ion channel
function of the viral M2 protein. Viral resistance to both
compounds is associated with changes in the M2 protein.
Although the rapid emergence of resistant viruses has been
demonstrated both in vitro and in vivo, the risk of transmission
of these resistant viruses remains unclear. Resistant viruses
have been most often isolated from individuals receiving
treatment and less often from contacts.
When administered prophylactically, both agents are
~7090% effective in preventing illness caused by influenza A
viruses. Subclinical infections still can occur while taking these
drugs. Although chemoprophylaxis can be used alone in persons
for whom vaccination is contraindicated, it is preferable to
administer these agents as an adjunct to vaccination in highrisk groups. Since these drugs do not interfere with antibody
response to vaccination, they can be used to provide
excreted).
dysfunction
(for
rimantadine).
Prognosis
In most cases, illness from influenza resolves within a week, but
cough and malaise may persist for several days to a few weeks
longer. In a minority of patients, fatigue may persist for
months.
Prevention
&
Control
viruses
exhibit
ongoing
antigenic
P.385
NA=Not applicable.
*Adapted from CDC. Prevention and control of influenza:
recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Morbid Mortal Weekly Rep 2001 (In
press).
Age
Antiviral
Agent
16
years
79
years
(years)
1012
years
1364
years
65
years
hospitalization,
pneumonia,
and
death.
B.
infants. Breastfeeding does not adversely affect
immune response and is not a contraindication for
vaccination.
C . Persons traveling to foreign countries: Exposure risk
varies by season and destination. In the tropics,
influenza can occur throughout the year; in the
Southern Hemisphere, most activity occurs from
April through September. Because of the short
incubation period for influenza, exposure to the
virus during travel can result in clinical illness that
begins while traveling, which can be a potential
danger, in particular for persons at increased risk
for complications.
Persons preparing to travel to the tropics at any
time of year, or to the Southern Hemisphere from
April through September should review their
influenza vaccination histories and, if not vaccinated
the previous fall or winter, should consider influenza
vaccination before travel. Persons in high-risk
groups should be especially encouraged to receive
the most current vaccine. Persons at high risk who
received the previous season's vaccine before travel
should be revaccinated in the fall or winter with the
current vaccine.
D . Among the general population:
Anyone who wishes to avoid influenza.
Persons who provide essential community
services (to minimize disruption of essential
activities during influenza outbreaks).
Students or other persons in institutional
settings (eg, those who reside in dormitories), in
order to minimize the disruption of routine
activities during epidemics.
IV. Persons who should NOT be vaccinated:
Persons with known anaphylactic hypersensitivity to
eggs or to other components of the influenza vaccine
(use of antiviral agent is optional at preventing
REFERENCES
Arruda E, Hayden FG: Update on therapy of influenza and
rhinovirus infections. In Mill J et al: Antiviral
Chemotherapy ,
Elsevier,
1996;1/75.
Betts RF: Influenza Virus. In Mandell: Principles
Practices of Infectious Diseases , 1995;1546.
and
1996;275:295.
2001
McGraw-Hill
Virus
30
Parainfluenza
Virus
Gregory Sonnen MD
Nancy Henry MD, PhD
Essentials
Ubiquitous
of
viral
Diagnosis
agent.
laryngotracheobronchitis
General
Considerations
solvents.
CLINICAL
SYNDROMES
ACUTE
LARYNGOTRACHEOBRONCHITIS
(CROUP)
Clinical
Findings
Common
Acute
laryngotracheobronchitis
(croup)
Common
Bronchiolitis
Pneumonia
Pneumonia
(primarily
Children
Adults
BOX
30-1
the
Parainfluenza
elderly)
Syndromes
Diagnosis
Croup is usually diagnosed based on history and physical
examination alone. Radiography can help confirm the diagnosis
but is often not needed.
Treatment
Treatment is aimed at reducing upper airway edema and
inflammation to optimize the upper airway (Box 30-2 ). In the
vast majority of cases, cool, humidified air is optimal. Home use
of a humidifier in the child's room is an optimal home therapy.
If the child is in distress or fails to respond to humidified air,
nebulized racemic epinephrine is indicated. If racemic
epinephrine is used, the patient should be closely observed for
an appropriate amount of time (usually 4 h). Some patients will
experience a rebound swelling of the laryngeal mucosa
after epinephrine administration. Dexamethasone, administered
either orally or intramuscularly, will help reduce inflammation
and prevent recurrence of symptoms. Dexamethasone is
preferred for its long half-life. An inhaled helium-oxygen
mixture can be helpful in refractory cases. Nebulized
budesonide is very efficacious, but is not yet FDA approved for
use in the United States. Intubation is indicated for severe
laryngotracheobronchitis
(croup)
Syndrome
Table
30-1.
Age
Clinical
Findings
Parainfluenzaclinical
findings.
BRONCHIOLITIS
Clinical
Findings
Croup
care
Diagnosis
Bronchiolitis is usually diagnosed based on history and physical
examination alone (see Table 30-1 ). Air trapping will result in
hyperexpansion as revealed by chest radiography. Hypoxia and
Treatment
Therapy is aimed at maintaining oxygenation and adequate air
exchange. Supportive care is effective in the vast majority of
cases. Tachypneic infants will have increased insensible fluid
losses. Intravenous fluids may be needed if dehydration is
present. Nasal suctioning to maintain clear nasal passages is
warranted in all infants. Oxygen should be provided immediately
if hypoxia is present. Bronchodilators may provide some benefit.
Mechanical ventilation is indicated if signs of respiratory failure
are present. Corticosteroids will be of benefit if the patient has
asthma.
PNEUMONIA
Clinical
Findings
Diagnosis
Diagnosis is based on physical and radiographic evidence (see
Table 30-1 ). The etiology of pneumonia may be difficult to
differentiate, especially in children. A sputum sample is often
difficult to obtain from infants and toddlers. If a bacterial source
cannot be ruled out, antibiotics are warranted.
P.391
Treatment
Antibiotics should be used to cover all appropriate community
acquired pneumonias unless a specific etiology can be isolated.
Oxygen should be used for hypoxia. Mechanical ventilation
should be utilized for respiratory failure.
Prevention
&
Control
Measures
Handwashing
No vaccine currently available
Isolation
Precautions
REFERENCES
American Academy of Pediatrics, Committee on Infectious
immunocompromised
2001
McGraw-Hill
Syncytial
Virus
31
Respiratory
Syncytial
Virus
Gregory Sonnen MD
Nancy Henry MD, PhD
Essentials
of
Diagnosis
reinfection
occurs
throughout
life.
General
Considerations
CLINICAL
SYNDROMES
BROANCHIOLITIS
Clinical
Findings
infiltrates
Differential
Diagnosis. The differential diagnosis of
bronchiolitis includes pneumonia, asthma exacerbation,
foreign-body aspiration, and noxious-chemical inhalation.
Complications. In healthy infants, the disease lasts 37
days. Children with an underlying pulmonary or cardiac
disease can have prolonged courses lasting weeks.
Recurrent episodes of wheezing
P.393
of
pulmonary
hyperinflation
Pneumonia
Infants, toddlers, & the elderly
Respiratory
distress
Diffuse, fine rales
Radiographic evidence
Fever
Syndrome
Age Group
of
diffuse
Clinical
interstitial
Findings
infiltrates
Table
PNEUMONIA
Signs and Symptoms. Pneumonia from RSV typically
occurs in infants and the elderly. Typical presenting
symptoms may include fever, dyspnea, tachypnea, and
hypoxemia. Diffuse, fine rales may be auscultated.
Laboratory
bronchiolitis
may be difficult.
Complications. Patients with underlying pulmonary,
immunologic, and cardiac disease are at risk for serious
morbidity.
More
Common
Common
Otitis
media
Tracheobronchitis
Pneumonia (primarily
the
elderly)
Diagnosis
Diagnosis of most RSV infections is based on physical and
radiographic findings (see Table 31-1 ). Rapid antigen detection
is often helpful, especially in compromised infants. Evidence of
hypoxemia at presentation warrants aggressive therapy.
Treatment
Therapy is aimed at maintaining oxygenation and adequate air
exchange. Supportive care is effective in the vast majority of
cases. Tachypneic infants will have increased insensible fluid
losses. Intravenous fluids may be needed if dehydration is
present. Nasal suctioning to maintain clear nasal passages is
warranted in all infants. Oxygen should be provided immediately
P.394
P.395
if hypoxia is present. Bronchodilators may provide some benefit
in bronchiolitis. Mechanical ventilation is indicated if signs of
respiratory failure are present. Corticosteroids will benefit if the
patient has asthma.
Supportive
Care
Ventilation
Respiratory
failure
Intramuscular
Indications
Dosage
Prevention
&
Control
Thorough hand washing will limit the spread of RSV (Box 31-3 ).
Measures
Precautions
REFERENCES
American Academy of Pediatrics, Committee on Infectious
Diseases: Prevention of RSV: Indications for the use of
Palivizumab and update on the use of RSV-IGIV. Pediatrics
1998;102:1211.
American Academy of Pediatrics, Committee on Infectious
Diseases: Reassessment of indications for ribavirin therapy.
Pediatrics 1996;97:137.
1992.
2001
McGraw-Hill
32
Adenoviruses
Lawrence W. Drew MD, PhD
Essentials
Respiratory
Disseminated
Intranuclear
of
Diagnosis
symptoms
infection
inclusions
(plus
in
in
conjunctivitis).
immunocompromised
infected
epithelial
patients.
cells;
General
Considerations
P.397
viral DNA and protein. In addition to inclusions, adenovirus
infections are characterized by mononuclear cell infiltrates
and epithelial cell necrosis. Type-specific neutralizing
antibody is associated with protection from reinfection.
CLINICAL
SYNDROMES
ACUTE
RESPIRATORY
DISEASE
Children
More
common
Upper
respiratory
infection
Adults
Acute respiratory
disease
Conjunctivitis
Pharyngitis
Conjunctivitis
Less
common
Hemorrhagic
cystitis
Systemic infection in
immunocompromised
Pneumonia
Diarrhea
Pertussislike
illness
patients
Pneumonia
CONJUNCTIVITIS
Signs and Symptoms. Adenoviruses cause a follicular
conjunctivitis in which the mucosa of the palpebral
conjunctiva becomes pebbled or nodular, while both
conjunctivae (palpebral and bulbar) become inflamed.
Conjunctivitis may occur sporadically or in outbreaks that can
be traced to a common source, eg, swimming pools. Corneal
involvement may occur with mechanical irritation of the eye
and is most striking when it spreads in epidemic form, eg,
shipyard conjunctivitis, also described as epidemic
keratoconjunctivitis.
Differential
Diagnosis. Adenovirus conjunctivitis is
frequently bilateral and has a granular or follicular
appearance. C trachomatis conjunctivitis is similar but is
more severe in the bulbar conjunctiva than is adenovirus.
Coexisting acute respiratory disease suggests adenovirus, as
does preauricular adenopathy.
Complications
Keratitis may develop as the conjunctivitis subsides and may
persist for months.
ACUTE
GASTROENTERITIS
are
Complications
Although mesenteric adenitis and intussusception may be
complications of adenovirus infections, these associations
remain unproven.
Table
Clinical
Acute
Syndrome
febrile
Patient
Group
1, 2, 3, 4,
5, 7a
Young
children
5a
Older
children
2, 3, 4, 5,
7, 8, 11,
14, 21
Military
recruits
Conjunctivitis
3, 7, 8, 9,
19
Children
and
adults
Acute
40, 41
Infants
11, 21
Young
children
1, 2, 4, 5,
6, 7, 7a,
11, 31, 32,
34, 35
Children
and
adults
Pharyngo
fever
pharyngitis
Virus
Serotypes
conjuntival
Acute
gastroenteritis
hemorrhagic
cystitis
Systemic infection in
immunocompromised
patients
1 Highlighted
disease
P.398
ACUTE
HEMORRHAGIC
CYSTITIS
days.
Laboratory
Findings. Gross and, subsequently, microscopic
hematuria is present for several days.
Imaging
No renal or bladder abnormalities are present in x-rays.
Differential
SYSTEMIC INFECTION IN
IMMUNOCOMPROMISED
PATIENTS
Immunocompromised patients (especially transplant recipients)
are at risk of serious adenovirus infections, although not as often
as from infections caused by the herpes viruses. Diseases include
pneumonia and hepatitis as well as disseminated disease. These
illnesses are severe and may be fatal. Infection appears to be
from exogenous or endogenous (reactivation) sources. In AIDS
patients, adenoviruses appear to be responsible for
gastrointestinal disease, as revealed by biopsy. Adenoviruses are
also recovered from urine or semen of AIDS patients, but their
significance is unknown. There is no known effective treatment
for adenovirus infections in patients.
Diagnosis
of
Adenovirus
Infection
pyogenes.
Prophylactic
Isolation
measures
precautions
Vaccine
(military
Respiratory,
recruits)
enteric
P.399
Prevention
&
Control
REFERENCES
Fox JP, Hall CE, Cooney M: The Seattle Virus Watch. VII.
Observations of adenovirus infections. Am J Epidemiol
1977;105:362. (The definitive study of adenovirus respiratory
infection in civilians.).
Hierholzer JC: Adenoviruses in the immunocompromised host.
Clin Microbiol Rev 1992;5:262.
2001
McGraw-Hill
33
Herpesviruses
Lawrence W. Drew MD, PhD
The herpesvirus group of the family Herpesviridae comprises large,
enveloped, double-stranded DNA viruses found in both animals and
humans. They are ubiquitous and produce infections ranging from
painful skin ulcers to chickenpox to encephalitis. The major
members of the group to infect humans are the two herpes simplex
viruses (HSV-1 and -2), cytomegalovirus (CMV), varicella-zoster
virus (VZV), Epstein-Barr virus (EBV), herpesvirus 6, and the
recently discovered human herpesvirus types 7 and 8.
Occasionally, the simian herpesvirus, herpes B virus, has caused
human disease.
All herpesviruses are morphologically similar with an overall
diameter of 180200 nm. The nucleic acid core is ~ 3045 nm
in diameter, surrounded by an icosahedral capsid. The capsid is
covered by a tegument and a lipoprotein envelope derived from the
nuclear membrane of the infected host cell. The envelope contains
at least nine glycoproteins that protrude beyond it as spikelike
structures, while the tegument is a protein-filled area between the
capsid and the envelope. Despite the morphologic similarity
between these agents, substantial differences in the molecular
composition of their genomes are reflected in their structural
HERPES
SIMPLEX
Essentials
of
VIRUS
Diagnosis
General
Considerations
Epidemiology
The term herpes (from the Greek herpein, to creep) and the
clinical description of cold sores date back to Hippocrates. Two
distinct epidemiologic and antigenic types of HSVs exist (HSV-1
and HSV-2). HSVs have worldwide
known animal vectors, and humans
natural reservoir (Box 33-1 shows
HSV). Direct contact with infected
mode of spread. Seroepidemiologic
Immunity
Host factors have a major effect on
HSV infection. Many episodes of HSV
asymptomatic or mildly symptomatic.
of the disease are symptomatic, they
recurrent episodes, probably because
clinical manifestations of
infection are either
If initial clinical episodes
are more severe than
of the presence of anti-
Children
More
Common
Less
Common
Adults
Mucocutaneous
lesions, oral or
genital
HSV
stomatitis
HSV
encephalitis
HSV meningitis,
encephalitis
HSV
disseminated
CLINICAL
SYNDROMES
P.403
3.
NEONATAL
HERPES
Diagnosis
Herpes simplex virus is easily isolated from lesions or tissue by
using fibroblasts or a variety of other tissue culture cells. The
cytopathic effects of HSV can usually be demonstrated 2448 h
after inoculation. Isolates of HSV-1 and HSV-2 (see below) can be
differentiated by staining virus-infected cells with type-specific
monoclonal antibodies to the two types or by analyzing restriction
enzyme digests of purified viral DNA. Restriction endonuclease
digests can also be used to define epidemiologic relationships, that
is, identify strains acquired between sexual partners or through
mother-infant transmission. A direct smear prepared from the base
Children
First
Choice
Second
Choice
Acyclovir
Adults
Acyclovir
Valacyclovir
Famciclovir
Treatment
Several antiviral drugs have been developed that inhibit HSV (Box
33-2). The most commonly used is the nucleoside analog acyclovir,
which is converted by a viral enzyme (thymidine kinase) to a
monophosphate and then by cellular enzymes to the triphosphate
Prognosis
At least 80% of patients with clinically evident primary HSV
infection develop recurrent episodes of herpes within 12 months.
In patients whose lesions recur, the median number of recurrences
is four or five per year. They are not evenly spaced, and some
patients experience a succession of monthly attacks followed by a
period of quiescence. Most recurrences result from reactivation of
virus from dorsal root ganglia. Rarely, recurrent diseases may be
caused by reinfection with a different strain of HSV. Ultimately
recurrences of herpes diminish in frequency, especially with genital
HSV-2 infection. Genital HSV-1 infection recurs to recur less
frequently.
If untreated, HSV-1 encephalitis has a mortality of 70%, but
intravenous acyclovir reduces mortality especially if given before
coma occurs.
Because a normal immune response is absent in the neonate,
neonatal HSV infection is an extremely severe disease with an
overall mortality of ~ 60%, and neurologic sequelae are high in
those who survive.
Prevention
&
Control
Prophylactic
Measures
VARICELLA-ZOSTER
Essentials
of
VIRUS
Diagnosis
or
shingles)
General
Considerations
Epidemiology
VZV infection, the cause of both varicella (chickenpox) and
herpes zoster, is ubiquitous (Box 33-4). Nearly all persons
contract chickenpox before adulthood, and 90% of cases occur
before the age of 10. The virus is highly contagious, with
attack rates among susceptible contacts of 75%. Varicella
occurs most frequently during the winter and spring months.
The incubation period is 1121 days. The major mode of
transmission is respiratory, although direct contact with
vesicular or pustular lesions may result in transmission.
Infectivity is greatest 2448 h before the onset of rash and
lasts 34 days into the rash. Virus is rarely isolated from
crusted lesions.
Microbiology
VZV has the same general structure as HSV but has its own
DNA sequence and envelope glycoproteins. Cellular features of
infected cells, such as multinucleated giant cells and
intranuclear eosinophilic inclusion bodies, are similar to those
of HSV-infected cells. VZV is more difficult to isolate in cell
culture than HSV and grows best but slowly in human diploid
fibroblast cells.
Pathogenesis
The viruses isolated from lesions of chickenpox and zoster (or
shingles) are identical. Latency of VZV occurs in sensory
ganglia, as shown by in situ hybridization detection of viral
DNA in dorsal root ganglia of adults many years after varicella
infection.
Immunity
Both humoral immunity and cell-mediated immunity are
important factors in determining the frequency of reactivation
and severity of varicella-zoster. Circulating antibody prevents
reinfection, and cell-mediated immunity appears to control
reactivation. In patients with depressed cell-mediated immune
responses, especially those who have received bone marrow
transplants or have Hodgkin's disease, AIDS, or
lymphoproliferative disorders, reactivation can occur, and be
severe.
Children
Adults
More
Common
Varicella
Zoster
(shingles)
Less
Common
Zoster (shin
gles)
VZ encephalitis
Varicella
VZ encephalitis
Clinical
Findings
pneumonia.
Complications
The complications of VZV infection are varied and depend on age
and host immune factors. Post-herpetic neuralgia is a common
complication of herpes zoster in elderly adults. It involves
persistence of severe pain in the dermatome after resolution of the
skin lesions and appears to result from damage to the involved
nerve root. Immunosuppressed patients may develop disseminated
lesions with visceral infection, which resembles progressive
Diagnosis
Varicella or herpes zoster lesions can usually be diagnosed
clinically. Scrapings or swabs from the base of lesions may reveal
characteristic cells with intranuclear inclusions or multinucleated
giant cells identical to those produced by HSV. VZ virus can be
isolated from aspirated vesicular fluid inoculated onto human
diploid fibroblasts; however, the virus is difficult to grow from
zoster (shingles) lesions older than 5 days, and cytopathic effects
are usually not seen for 59 days. For rapid viral diagnosis,
varicella zoster antigen may be demonstrated in cells from lesions
by immunofluorescent antibody staining. PCR analysis of CSF may
be useful to diagnose VZV encephalitis; cultures are rarely positive.
Treatment
Acyclovir has been shown to reduce fever and skin lesions in
patients with varicella (Box 33-5), and its use is recommended in
healthy patients over 18 years of age if treatment is begun within
2448 h of onset of rash. There is insufficient data to justify
universal treatment of all healthy children and teenagers with
antiviral agents. In immunosuppressed patients, controlled trials of
acyclovir have shown efficacy in reducing dissemination, and its
use is definitely indicated. In addition, controlled trials of acyclovir
have demonstrated effectiveness in the treatment of herpes zoster
in immunocompromised patients. Acyclovir may be used to treat
herpes zoster in immunocompetent adults, but it appears to have
little or no impact on the development of post-herpetic neuralgia,
the most important complication of zoster. Treatment should be
started within 3 days of the onset of zoster. VZ virus is less
susceptible than HSV to acyclovir, so the dosage for treatment is
substantially higher. Famciclovir or valacyclovir are more
convenient and may be more effective in preventing post-herpetic
Children
First
Choice
Adults
Acyclovir for
children > 12
years who
have varicella
Varicella:
acyclovir,
800 mg 5
times/day
but no definite
consensus
Zoster:
acyclovir,
800 mg 5
times/ day;
famciclovir,
500 mg/8 h;
or
valacyclovir,
1.0 g 3
times/day
Pediatric
Considerations
Prevention
&
An antiviral
agent is not
recommended
for children
<12 years
Control
Prophylactic
Measures
Isolation
Precautions
CYTOMEGALOVIRUS
Essentials
of
Diagnosis
General
Considerations
Epidemiology
CMV is ubiquitous, and in developed countries ~50% of adults
have developed antibody (Box 33-7). Age-specific prevalence
rates show that ~ 1015% of children are infected by CMV
during the first 5 years of life, after which the rate of new
infections levels off. The rate subsequently increases during
young adulthood, probably through close personal contact or
sexual transmission of the virus. CMV has been isolated from
saliva, cervical secretions, semen, urine, and white blood cells.
Excretion of virus is prolonged after congenital and perinatal
infections, probably because of immunologic tolerance, and
high titers of virus may be shed for more than 5 years after
birth. Transmission of infection in daycare centers has been
shown to occur from asymptomatic excretors to other children
and
immunopathogenic
mechanisms
Children
More
Perinatal
Common
infection,
Daycare
infection
Less
Common
Congenital
infection
Adults
Clinical
Findings
organs.
Diagnosis
Laboratory diagnosis of CMV infection depends on (1) detecting
CMV cytopathology, antigen, or DNA in infected tissues or bodily
fluids, (2) isolating the virus from tissue or bodily fluids, or (3)
demonstrating seroconversion. CMV can be grown in serially
propagated diploid fibroblast cell lines but generally requires
314 days, depending on the concentration of virus in the
specimen. The time for detection can be shortened by
centrifugation and immune staining, but culture of blood is less
sensitive than antigenemia or DNA-based assays.
Because of the high prevalence of asymptomatic carriers and the
known tendency of CMV to persist weeks or months in infected
individuals, it may be difficult to attribute a specific disease to CMV
by isolation of the virus from a peripheral site. Thus, the isolation
of CMV from urine of immunosuppressed patients with interstitial
pneumonia does not constitute evidence for CMV as the etiology of
that illness. CMV pneumonia or gastrointestinal disease is best
diagnosed by demonstrating CMV inclusions in biopsy tissue.
Treatment
Ganciclovir, a nucleoside analog of acyclovir, inhibits CMV
replication and reduces the severity of CMV syndromes, such as
retinitis and gastrointestinal disease (Box 33-8). When given with
hyper immune globulin, ganciclovir is thought to reduce the
mortality of CMV pneumonia in transplant recipients.
Foscarnet is an approved drug for therapy of CMV retinitis. Its toxic
effects are primarily renal with electrolyte disturbances, whereas
ganciclovir is most apt to inhibit bone marrow function. Ganciclovir
inhibits CMV DNA polymerase as does foscarnet, but they act on
different sites and cross-resistance is rare. Cidofovir is a third
approved anti-CMV drug and is the first nucleotide analog to be
used in clinical practice. It has a long half-life, which allows it to be
Prevention
&
Control
Children
First
Choice
Second
Ganciclovir
Choice
Pediatric
Considerations
Adults
Ganciclovir, 5
mg/kg/d IV or
valgauciclovir
9001800 mg orally
No experience
with treat
ments other
than ganciclovir
Prophylactic
Measures
EPSTEIN-BARR
Essentials
of
VIRUS
Diagnosis
General
Considerations
Children
Adults
More
Common
Infectious
Less
Common
EBV
lymphoproliferaliferative
EBV
lymphoproliferative
disease
disease
Clinical
mononucleosis
Findings
Diagnosis
Laboratory confirmation of EBV infectious mononucleosis is usually
Treatment
Treatment of infectious mononucleosis is largely supportive. More
than 95% of patients recover uneventfully. In a small percentage
of patients, splenic rupture may occur; thus, restriction of contact
sports or heavy lifting during the acute illness is recommended.
The DNA polymerase enzyme of EBV has been shown to be
sensitive to acyclovir, and acyclovir can decrease the amount of
replication of EBV in tissue culture and in vivo (Box 33-11) .
Despite this antiviral activity, systemic acyclovir makes little
impact on the clinical illness. Corticosteroids appear to be
beneficial in reducing laryngeal edema and severe toxicity. They
may also be indicated for CNS complications. Treatment of EBV
lymphoproliferative disease includes diminution of
immunosuppression as much as possible; acyclovir is also used.
First
Choice
None
Second
Choice
Prevention
&
transplant
Control
HUMAN
conditions.
HERPESVIRUS
Essentials
of
TYPE
Diagnosis
defervescence
General
Considerations
More
Common
Exanthem
subitum
Less
Meningitis,
encephalitis
Common
recipients
fever
in
transplant
Clinical
Findings
Diagnosis
Virus infection is best documented by seroconversion. Active virus
infection can be documented by culture, antigenemia, or DNAemia,
but since reactivation or is common, it is very difficult to use these
tools to diagnose HHV-6 as the cause of disease. Also, culture
takes 1030 days.
Treatment
HHV-6 appears to be susceptible in vitro to ganciclovir and
foscarnet and less susceptible to acyclovir, but no clinical data are
available.
Prevention
&
Control
OTHER
HERPESVIRUSES
1. HERPESVIRUS TYPE 7
Isolation of human herpesvirus type 7 (HHV-7) was first reported
in 1990. The virus was isolated from activated CD4+ T lymphocytes
of a healthy individual. HHV-7 is distinct from all other known
human herpesviruses but is most closely related to HHV-6.
Seroepidemiologic studies indicate that this virus usually does not
infect children until after infancy, and ~ 50% of infants are
antibody positive by 24 years of age. As with HHV-6 this virus is
frequently isolated from saliva, and close personal contact is the
probable means of transmission. Also like HHV-6 this virus appears
to be a cause of exanthem subitum. The diagnosis of acute
REFERENCES
Benedetti J et al: Recurrence rates in genital herpes after
symptomatic first episode infection. Ann Intern Med
1994;121:847. (Acyclovir treatment of first episodes does not
decrease recurrence rates; higher recurrence rates are reported
in men, which partly explains higher transmission rates from
men to women.).
Caserta MT, Hall CB, Schnabel K et al: Neuroinvasion and
persistence of human herpesvirus 6 in children. J Infect Dis
1994;170:1586.
Cone RW, Hackman RC, Huang MW et al: Human herpesvirus 6
in lung tissue form patients with pneumonitis after bone marrow
transplantation. N Engl J Med 1993;329:156.
DeRodriguez W, Fuhrer J: Cytomegalovirus colitis in patients
1991;77:1104.
P.412
2001
McGraw-Hill
34
Measles
Gregory Sonnen MD
Nancy Henry MD, PhD
Essentials
of
Diagnosis
General
Considerations
CLINICAL
TYPICAL
Clinical
SYNDROMES
MEASLES
Findings
measles
infection
Rare
Incomplete live-virus vaccination series followed by
natural
measles
infection
Rare
Inactivated measles vaccination,
to natural measles virus
followed
by
exposure
Incubation
812 d
Similar to typical measles
12
Prodromal
weeks
phase
Exanthem
phase
confluence
Modified
Measles
Atypical
Measles
Laboratory
Findings. The virus can be isolated from a
nasopharyngeal swab, conjunctival swab, blood, and urine
during the febrile course of the illness. Isolation of the virus
can be technically difficult. A variety of tissue cultures can
be used to grow the virus. Human and monkey kidney cell
lines are typically used with clinical specimens. Acute and
convalescent serologies can be helpful. Serologies should be
drawn 24 weeks apart to monitor progression.
Immunoglobulin M (IgM) is detectable from 3 to 30 days
More
Common
Meningoencephalitis
Pneumonia
Otitis media
Laryngotracheitis
Less
Common
Supportive
Care
Globulin
confirmed
immunity
Vaccine
Dosage
MODIFIED
MEASLES
Vaccine
Contraindications
Pregnancy
Febrile illness
Planned pregnancy within 3 months
Severe immunocompromised state
Blood product or immune globulin within 3 to 6 months
(dose dependent)
Anaphylaxis to neomycin
Precautions
ATYPICAL
MEASLES
Diagnosis
Diagnosis of measles is usually based on physical findings.
Finding Koplik's spots and monitoring the usual progression of
the exanthem are helpful clues. An attempt should be made to
culture the virus during the febrile course of the illness. Culture
can often be technically difficult. Serology should be obtained as
well. Confirmation of a diagnosis should be promptly reported to
a local government health agency for epidemiologic tracking.
Treatment
Treatment of measles is often supportive. Hospitalization is not
warranted unless the patient is dehydrated, in respiratory
distress, encephalopathic, or otherwise compromised. Young
patients requiring hospitalization (Box 34-2 ) should receive
vitamin A. Recent clinical studies have shown a decrease in
morbidity and mortality in patients receiving vitamin A
supplementation. Patients of any age may benefit from vitamin
A supplementation if their cases are clinically severe. All
patients in areas of known vitamin A deficiency (ie, Third World
countries) should receive supplementation if measles is endemic
to the area.
Immune globulin may be used to protect susceptible contacts of
confirmed measles cases. Immune globulin must be used within
6 days of exposure for maximum efficacy. Contacts who
received at least one dose of measles vaccine at age 12
months do not need immune globulin if they are
immunocompetent. Candidates for immune globulin would
include nonimmunized pregnant women, the
immunocompromised, and infants < 1 year of age. Infants < 5
months of age do have passive maternal antibodies if
P.417
their mother can be confirmed to be measles immune. If
maternal immunity is confirmed, these infants do not need
immune globulin. If children receive immune globulin, they
should not receive measles vaccine for 5 months (if receiving
0.25 cc/kg immune globulin) or 6 months (if receiving 0.5 cc/kg
immune globulin).
The live virus vaccine can modify the infection in a
nonimmunized person, if given within 72 h of exposure. Clinical
response varies. Usual vaccine contraindications apply to the
Prevention
&
Control
REFERENCES
American
Diseases:
Report of
American
2001
McGraw-Hill
35
Mumps
Gregory Sonnen MD
Nancy Henry MD, PhD
Essentials
of
Diagnosis
General
Considerations
Epidemiology
Mumps, historically known as epidemic parotitis, was one of
the most common early childhood infections before the
routine use of mumps vaccination starting in 1968. Reported
cases of mumps have dropped 98% when compared with the
More
Common
Less
Common
Meningoencephalitis
Deafness
Arthritis
Pancreatitis
Thyroiditis
Mastitis
Oophoritis
Clinical
Findings
pancreatitis,
thyroiditis,
mastitis,
and
oophoritis.
Maintain hydration
Analgesics
Opioids often needed for severe orchitis
Lumbar puncture can be therapeutic for severe
headache
Mumps immune globulin is of little value, and no
longer available in the United States
Vaccine
If no preschool dose is
given, the second dose
should be administered
before age 12
MMR Vaccine
Contraindications
Pregnancy
Febrile illness
Planned pregnancy within 3
months
Severe
immunocompromised
state
Blood product or immune
globulin within 3 to 6
months (dose dependent)
Anaphylaxis to neomycin
MMR Vaccine
Should Be Used
Seizure disorder
Thrombocytopenia
with Caution in
These Situations
Egg allergy
Isolation
Precautions
Respiratory
isolation
should be maintained for 9
days after onset of
parotitis
Infected children should be
excluded from school and
daycare during this period
Diagnosis
Diagnosis is based on physical findings and culture or serology.
History of a mumps contact can be difficult to find owing to the
significant number of subclinical cases. Cerebrospinal fluid will
demonstrate a lymphocytic pleocytosis if meningitis is present.
Treatment
Therapy is aimed primarily at analgesia (Box 35-2). Opioids are
often needed for the pain of orchitis, which can be quite severe.
Local application of cool compresses may also help relieve some
of the orchitis pain. Intravenous hydration may be needed for
some patients. Lumbar puncture may be therapeutic for patients
with severe headache. Mumps immune globulin has little clinical
value. It is no longer available in the United States.
Prevention
&
Control
REFERENCES
American
Diseases:
Report of
American
2001
McGraw-Hill
36
Rubella
Gregory Sonnen MD
Nancy Henry MD, PhD
General
Considerations
gestation.
Microbiology. Rubella is a 70-nm single-stranded RNA virus
of the Togaviridae family. It is the only virus in the genus
Rubivirus. It has three polypeptide constituents (E1, E2, and
C). E1 and E2 are glycosylated membrane peptides. The
nucleocapsid is composed of polypeptide C and genomic
RNA. The viral envelope is a lipoprotein complex. The virus
is sensitive to heat, light, and pH extremes.
Pathogenesis. Humans are the only natural reservoir of the
virus. Spread is chiefly via respiratory secretions and direct
contact. The virus is communicable for 35 days before
the rash and 7 days after the rash has appeared. The virus
has a latent phase of 23 weeks before clinical disease
appears.
POSTNATALLY
ACQUIRED
Essentials
Diagnosis
of
Exanthematous
viral
RUBELLA
illness.
Clinical
Findings
single
Diagnosis
Postnatally acquired rubella is diagnosed based on history and
physical findings (see Box 36-1 ). All suspected cases that are
Symptoms
and
diarrhea
Phase
Signs
Lymphadenopathy
and suboccipital
is
common,
typically
posterior
auricular
Mild,
transient
leukopenia
Complications
Encephalitis
Thrombocytopenia
Myocarditis
Erythema
multiforme
Congenital rubella syndrome
Children
Adults
Treatment
Postnatally acquired rubella requires no specific treatment.
Therapy should be symptomatic (Box 36-2 ). Use of
immunoglobulin as postexposure prophylaxis in nonimmune
patients is controversial. Routine administration of
immunoglobulin for postexposure prophylaxis of rubella is not
recommended. Symptoms in the mother may be reduced, but
fetopathy may still occur. Immunoglobulin may be considered in
cases where pregnancy termination was indicated but not
possible.
CONGENITAL
Essentials
Polysystemic
of
RUBELLA
SYNDROME
Diagnosis
fetopathy.
fetus.
Common defects include cataracts, deafness,
heart defects, hepatosplenomegaly.
microcephaly,
Clinical
Findings
Supportive care
Manage fever with acetaminophen (1015 mg/kg every 4
h orally or rectally) or ibuprofen (6 to 8 mg/kg every 6 to 8
h orally)
Supportive care
Analgesia with NSAIDs
Antihistamines
for
pruritus
Children
(Postnatal
Neonates
Infection)
Adults
Nonimmune
Pregnant
Women
the
Blueberry
abnormalities
Complications
Mental retardation
Developmental
delay
Behavioral
disorders
Endocrinopathies
BOX 36-3 Congenital Rubella Syndrome
Diagnosis
CRS is diagnosed based on history and physical findings (see
Box 36-3 ). Some neonates, especially those affected later in
pregnancy, may appear normal
birth. Suspected CRS neonates
IgM drawn. Cultures should be
blood, urine, and cerebrospinal
Treatment
No medical therapy is available for CRS (but see Box 36-2 ).
Cardiac defects warrant early intervention by a pediatric
cardiologist. Early audiologic evaluation should be performed. A
physician experienced with patients who have developmental
disabilities should be involved. Early intervention for
developmental delays and mental retardation is important. The
primary care provider should be aware of potential
Vaccine
Contraindications
Pregnancy
Febrile illness
Planned pregnancy within 3 months
Severe immunocompromised state
Blood product or immune globulin within 3 to 6 months
(dose dependent)
Anaphylaxis to neomycin
MMR Vaccine Should Be Used with Caution in These
Situations
Seizure disorder
Thrombocytopenia
Egg allergy
Isolation
Precautions
REFERENCES
American
Diseases:
Report of
American
2001
McGraw-Hill
37
Rotavirus
Gregory M. Sonnen MD
Nancy Henry MD, PhD
Essentials
of
Diagnosis
General
Considerations
Clinical
More
Common
Less
Common
Hyper- or hyponatremic
dehydration
Transient lactose intolerance
Rhinitis
Wheezing
Cervical
lymphadenopathy
Serous otitis media
Primary
Treatment
Pediatric
Considerations
Diagnosis
Diagnosis of rotavirus is based on history and physical findings.
Since this virus produces a self-limiting disease in healthy
individuals, identification of the virus is not needed in most
cases. In immunocompromised patients, identification of an
etiology is a higher priority, and stool should be sent promptly
for analysis. Serum electrolytes and glucose should be
evaluated in patients with moderate to severe dehydration.
Treatment
The primary therapy for rotavirus gastroenteritis is hydration
(Box 37-2). If appropriate oral hydration can maintain fluid
balance, no other intervention is needed. Small children and
infants are prone to dehydration. Assessing the level of
dehydration is key to deciding on therapy. Oral rehydration is
appropriate for most children with mild to moderate
dehydration. Parenteral rehydration is often needed if oral
rehydration fails. Patients with severe dehydration warrant
Prophylactic
Measures
Hand washing
Disinfection or disposal of all
potential fomites
Breast feeding decreases the
severity of illness in young
children
An oral, live-attentuated
tetravalent vaccine will be
commercially licensed in the very
near future for use in infants and
young
Isolation
Precautions
Prevention
children.
&
Control
REFERENCES
American Academy of Pediatrics, Committee on Infectious
Diseases: Rotavirus Infections. In Peter G (editor): 1997 Red
Book: Report of the Committee on Infectious Diseases, 24th
ed. American Academy of Pediatrics, 1997.
American Academy of Pediatrics, Provisional Committee on
Quality Improvement, Subcommittee on Acute
Gastroenteritis: Practice parameter: The management of
acute gastroenteritis in young children. Pediatrics
1996;97:424.
Kapikian AZ, Wyatt RG: Viral gastrointestinal infections. In
Feigin RD, Cherry JD (editors): Textbook of Pediatric
Infectious
Diseases, 3rd ed. Saunders, 1992.
Midthun K, Kapikian AZ: Rotavirus vaccines: An overview.
Clin Microbiol Rev 1996;9:423.
2001
McGraw-Hill
Gastrointestinal
Viruses
38
Other
Gastrointestinal
Viruses
HUMAN
ENTERIC
CALICIVIRUSES:
NORWALK & RELATED VIRUSES
Essentials
of
Diagnosis
General
Considerations
Clinical
Findings
Children
Adults
More
Common
Less
Astrovirus
Norwalk
Common
Adenovirus
virus
Children
First
Choice
Symptomatic
Adults
Symptomatic
Diagnosis
Culture. None of the Norwalk or human enteric caliciviruses
can be grown in tissue culture, although the development of
a sensitive culture assay is a high priority.
Direct Detection. Standard EM of feces is usually negative
for the Norwalk agent because they are present in low titer.
Other caliciviruses may be present in sufficient
Treatment (Box
38-2)
Prophylactic
Isolation
Measures
Precautions
Prognosis
Good
personal
hygiene
Prevention
&
Control (Box
38-3)
ASTROVIRUSES
General
Considerations
ADENOVIRUS
Adenoviruses, particularly the high numbered serotypes (38
and, especially, 40 and 41) are associated with gastroenteritis.
(See Chapter 32 for an extensive consideration of
adenoviruses.) The enteric adenoviruses are very difficult to
grow in tissue culture but are detected by EM or EIA. They
cause 515% of viral gastroenteritis in young children. The
average incubation period is 10 days, much longer than the
average of 12 days for the other viral causes of
gastroenteritis. Most disease is in infants and young children
and occurs sporadically rather than in outbreaks. The method of
spread is fecal-oral.
REFERENCES
the
2001
McGraw-Hill
39
Hepatitis
P.431
Lawrence W. Drew MD, PhD
The causes of hepatitis are varied and include viruses, bacteria, and protozo
as drugs and toxins (eg, isoniazid, carbon tetrachloride, and ethanol). The c
symptoms and course of acute
and determination of a specific
(Box 39-1 ). Hepatitis may be
characteristics are summarized
HEPATITIS
Essentials
A
of
Diagnosis
areas,
and
institutionalized
individuals.
Malaise, anorexia, fever, dark urine, pale stools, jaundice, right upper q
pain, and tender hepatomegaly.
General
Considerations
(picorna)virus with cubic symmetry and a diameter of 27 nm (Figure 39not inactivated by ether and is stable at -20C and low pH. These prop
similar to those of enteroviruses (see Chapter 27 ), but hepatitis A virus
and now classified in a separate genus, Hepatovirus. The virus has been
successfully cultivated in cell cultures but grows poorly.
P.432
in feces by electron microscopy for 1014 days before onset of disease
patients with symptoms of the disease, complete virus is no longer found
Kupffer cells. The extent of necrosis often coincides with the severity of
variable degree of biliary stasis may be present. Detectable levels of IgG
to hepatitis A virus persist indefinitely in serum, and patients with anti-h
virus antibodies are immune to reinfection.
More
Common
Common
Hepatitis C, G
Hepatitis D, E, G
Children
Adults
Clinical
Findings
days, jaundice. The patient may notice dark urine and clay-colored stool
days before the onset of clinical jaundice. The liver is enlarged and tend
persons who have serologic evidence of acute hepatitis A infection are
asymptomatic or only mildly ill, without jaundice (anicteric hepatitis A).
infection-to-disease ratio is dependent on age; it may be as high as 20:1
hepatic inflammation and damage. The serum bilirubin levels and prothr
are also elevated, the latter being a sensitive marker of hepatocyte dam
total leukocyte count is low because of neutropenia. Alkaline phosphatas
elevated especially in patients with a cholestatic picture, but it tends to
subsequently decrease even when the bilirubin is still rising.
A
47%
B
33%
C
15%
D
2%
Other
3%
Type
Table
A
0
0
B
1 106
5,000
C
1 105
810,000
D
7 104
1,000
E
0
0
Type
Cases/Year
Table
Differential
Diagnosis. All of the causes of acute hepatitis mentioned i
introduction to this chapter must be considered, but epidemiologic, age,
factors may help to predict a probable cause. See also Table 39-3 .
Figure
Incubation period
26 weeks (average 4 weeks)
623 weeks (average 10 weeks)
612 weeks
48 weeks
Virus
27-nm RNA virus
42-nm DNA virus
RNA, flavivirus
Incomplete RNA virus
RNA similar to Calicivirus
RNA similar to Hepatitis C virus
Onset
Abrupt (variable)
Insidious
(variable)
Insidious
(variable)
Abrupt (variable)
Acute
?
Transmission
Fecal-oral
IDU, sexual
IDU, sexual (?)/ household
IDU, sexual
Fecal-oral
Severity of acute infection
Self-limiting
Occasionally severe (up to 25% icteric)
Usually subclinical
Coinfection occasionally severe; superinfection
Self limiting, fulminant in pregnancy
?
often
severe
Fulminant Hepatitis
Very rare (~0.1%)
Rare (<1% of icteric patients)
Very rare, if ever
Yes
0.32%
Yes Very rare
?
Yes
12%
Chronicity
0%
510%
Up to 75%; cirrhosis (2533%); hepatoma
Up to 30% of those with chronic hepatitis B
No
Transmission by blood
Very rare
Rare with screening
transfusion
w/
cirrhosis
Yes, 20%
Yes, 40%
No
Rare
Associated
No
Yes
w/
hepatoCellular
cancer
Yes
?
No
?
Treatment of chronic disease
None
Interferon alpha; ? 3TC
Interferon alpha & ribavirin
Interferon alpha
?
None
indicated
Feature
Table
Hepatitis
Hepatitis
Hepatitis
Hepatitis
Hepatitis
P.433
Diagnosis
The best method for documentation of acute hepatitis A virus infection is the
demonstration of high titers of virus-specific IgM antibody in serum drawn d
acute phase of illness. Because IgG antibody persists indefinitely, its demon
a single serum sample is not indicative of recent infection; a rise in titer be
acute and convalescent sera must be documented. Immune electron microsc
identification of the viral antigen in fecal specimens and isolation of the virus
cultures remain research tools. Past infection is best demonstrated by anti-H
but absent IgM.
Treatment
Choice
Choice
Allergic
Children
Adults
Prognosis
The prognosis is excellent for > 99% of patients with hepatitis A infection. O
of patients develop fatal acute hepatic necrosis.
Prevention
&
Control
Passive
Immunization. Passive (ie, antibody) prophylaxis for hepatitis
been available for many years. Immune serum globulin (ISG), manufactu
pools of plasma from large segments of the general population, is 80
protective if given before or during the incubation period of the disease.
cases, infection occurs, but disease is ameliorated; that is, the patient d
anicteric,
usually
asymptomatic,
hepatitis
A.
Active
Immunization. For hepatitis A, live attenuated vaccines have be
evaluated but have demonstrated poor immunogenicity and have not be
HEPATITIS
Essentials
B
of
Diagnosis
Malaise, anorexia, fever, dark urine, pale stools, jaundice, right upper q
pain, and tender hepatomegaly.
General
Considerations
In the United States, it is estimated that 1.5 million people are infected
hepatitis B, and it is estimated that 300,000 new cases occur annually.
Approximately 300 of these individuals die with acute fulminant hepatitis
North and South America and Europe. The estimated risk of developing t
malignancy for persons with chronic hepatitis B is increased between 10fold in different populations. The mechanism of the association is unclea
The envelope of the virus contains HBsAg, which is composed of one maj
other proteins. Antigenically there exist a group-specific determinant, te
and a number of subtypes that are important in epidemiologic typing, but
immunity, because there is antigenic cross-reactivity and cross-protectio
subtypes. Aggregates of HBsAg are often found in great abundance in se
P.436
portions of the nucleocapsid. Hepatitis B DNA can also be detected in ser
an indication that infectious virions are present there. In infected liver t
evidence of HBcAg, HBeAg, and hepatitis B DNA is found in the nuclei of
hepatocytes, whereas HBsAg is found in cytoplasm.
results in the variable-length short positive DNA strands found in the vir
together with complementary negative long strands. Release is by a sec
mechanism (reverse
endocytosis) and does not cause cell lysis.
carcinomas. The virus has not been shown to possess a transforming gen
well activate a cellular oncogene. It is also possible that the virus does n
such a direct molecular role in oncogenicity, because the natural history
hepatitis B infection involves cycles of damage or death of liver cells in
Clinical
Findings
appetite, nausea and pain, and fullness in the right upper abdominal qu
Early in the course of disease, pain and swelling of the joints and occas
frank arthritis may occur. Some patients develop a rash. With increasing
In general, the symptoms associated with acute hepatitis B are more sev
more prolonged than those of hepatitis A; however, anicteric disease an
asymptomatic infection regularly occur. The infection-to-disease ratio, w
according to age and method of acquisition, has been estimated to be
approximately 6:1 or 7:1.
Laboratory
Findings. In acute illness, the laboratory findings are as w
hepatitis A; persistence of blood abnormalities beyond 6 months may ind
development of chronic hepatitis B disease.
Imaging. As with hepatitis A
Differential
with ongoing replication of virus in the liver and usually with the presenc
HBsAg in serum. Chronic hepatitis may lead to cirrhosis, liver failure,
hepatocellular carcinoma, or some combination of these. It is estimated
of all chronic liver disease in the United States and Canada is caused by
B. Fulminant hepatitis, leading to extensive liver necrosis and death, dev
~0.1% of cases.
Diagnosis
virions and high levels of DNA polymerase and HBeAg. Although HBcAg is al
antibody against it invariably occurs and prevents its detection. With resolut
acute hepatitis B, HBsAg and HBeAg disappear from serum with the developm
antibodies (anti-HBs and anti-HBe) against them. The
associated with elimination of infection and protection
detected early in the course of disease and persists in
excellent epidemiologic marker of infection but is not
development of anti-H
against reinfection. A
serum for years. It is
protective.
antibod
with h
Chroni
> 6
Treatment
viral-DNA levels are the most likely to respond to treatment. Lamivudine (3T
potent inhibitor of human immunodeficiency virus (HIV), is also active again
B virus, both in vitro and in initial clinical trials, but the virus can become re
this agent.
Prognosis
Ninety percent of acute hepatitis B cases resolve within 6 months; 0.1% are
to acute hepatic
P.438
necrosis; and ~10% progress to chronic hepatitis. Of these, 10% will
cirrhosis, hepatocellular carcinoma, or both.
Prevention
&
Control
Inactivated hepatitis B vaccines have been available for several years. The f
developed by purification and inactivation of HbsAg from the blood of chron
but this vaccine is no longer in use. The current vaccine is a recombinant pr
derived from HBAg grown in yeast. Excellent protection has been shown in s
homosexual men and medical personnel. These groups and others, such as
workers and injection drug users, who come into contact with blood or other
potentially infected materials, should receive hepatitis B vaccine as the pref
HEPATITIS
Essentials
of
(DELTA
HEPATITIS)
Diagnosis
General
Considerations
Clinical
Findings
Signs and Symptoms. Two major types of delta infection have been no
Differential
Diagnosis. Simultaneous infection with both delta and
results in clinical hepatitis that is indistinguishable from acute hepatit
however, fulminant hepatitis is much more common than with hepati
alone.
Figure 39-4. Schematic of delta hepatitis virus. Note outer layer derived fro
hepatitis B surface antigen. (Reprinted from Ryan KJ et al: Sherris Medical
Microbiology , 3rd ed. McGraw-Hill, 1994.)
Diagnosis
Treatment
Prognosis
Prevention
&
Control
HEPATITIS
Essentials
C
of
Diagnosis
asymptomatic
patient.
General
Considerations
Most NANB hepatitis is caused by an RNA virus termed hepatitis C virus. Its
and role in the etiology of hepatitis was identified by preparing numerous
complementary DNA clones from the presumed RNA virus in infectious serum
encoded by these clones were then tested for reaction with sera from cases
hepatitis, and one was found to be highly specific.
Clinical
Findings
P.440
Laboratory
Findings. Hepatitis C may be associated with elevated or n
values in serum.
Diagnosis
can be helpful in chronic hepatitis, especially when multiple antigens are sou
first test developed to assist the diagnosis of hepatitis C measured antibody
100 antigen of the virus. It is now acknowledged that this antibody is an in
marker for the disease, and current second-generation tests measure antibo
multiple hepatitis C antigens by either enzyme immunoassay or immunoblot
Even with these newer assays, IgG antibody to hepatitis C may not develop f
months, making the serodiagnosis of acute hepatitis C difficult. Assays of he
virus RNA by PCR or other methods may be used for diagnosis, estimating p
predicting interferon responsiveness, and monitoring therapy.
Treatment
Interferon alpha is approved for the treatment of chronic hepatitis C, but it
provides only a transient benefit (see Box 39-2 ). The commonly used dose
U 3 times weekly for 6 months. Amino transferase levels decrease in o
4070% of patients, but sustained improvement occurs in only 1015%
patients. Responses are better in patients with genotypes other than 1 and
Prognosis
Hepatitis C has a worse prognosis than, for example, hepatitis B, since such
proportion of cases develop cirrhosis 33% of infected patients.
Prevention
&
Control
HEPATITIS
General
E
Considerations
Hepatitis E is the cause of another form of hepatitis, but this virus is spread
fecal-oral route and therefore resembles hepatitis A. Hepatitis E virus is an
that appears similar to caliciviruses. The viral particles in stool are spherica
Measures
Preexposure:
Vaccination with killed vaccine
Immune serum globulin
Postexposure:
Immune
serum
globulin
Hepatitis B
Preexposure:
Vaccination with recombinant hepatitis B vaccine
Postexposure:
Hepatitis B immune globulin followed by vaccine
Hepatitis D
Vaccination with recombinant hepatitis B vaccine
Isolation
Precautions
Hepatitis A, E: enteric precautions
Hepatitis B, C, D: needle, blood precautions
BOX 39-3 Control of Hepatitis Infection
P.441
Diagnosis
IgM
antibody.
Treatment
No treatment is available for hepatitis E infection (see Box 39-2 ).
Prognosis
Prevention
&
Control
HEPATITIS
General
G
Considerations
Diagnosis
So far, it has not been possible to develop an antibody assay so that seropr
Treatment
REFERENCES
2001
McGraw-Hill
40
HIV & Other Retroviruses
Lawrence W. Drew MD, PhD
Essentials
of
Diagnosis
General
Considerations
Epidemiology
Two major groups of retroviruses are considered in this
chapter: the oncoviruses (onco-, related to a tumor)
and the lentiviruses (lenti-, slow). Oncoviruses have
Pathogenesis
Like most enveloped viruses, all retroviruses are highly
susceptible to inactivation and are thus not transmissible
through air, dust, or fomites under normal conditions; that
is, they require intimate, direct contact with tissue or bodily
fluids from the infecting source. Oncoviruses do not kill the
cell they infect but instead usually continue to produce new
virus indefinitely. This property, combined with the fact that
oncoviruses can transduce growth-promoting genes called
oncogenes into the recipient cell, accounts in part for the
ability of oncoviruses to cause malignancies.
With lentivirus infections, the cell-virus relationship is quite
different. Some lentiviruses can persist for years in a latent
state without causing much cell killing, only to become highly
cytolytic when the infected cells are subjected to certain
stimuli. The prototype lentivirus is the visna virus, which
causes a slowly degenerative neurologic disease in sheep.
Other lentiviruses, for example, HIV-1, can persistently
replicate at high levels resulting in cell death. Although HIV-1
can infect a variety of human cell types, its most drastic
effects appear to result from destruction of the CD4+
subclass of T lymphocytes, which play a central role in the
capacity of the host to mount effective immunologic
responses to a wide range of infections.
VIROLOGY
OF
THE
RETROVIRUSES
P.443
A comparison of the genetic makeup of HIV-1 with that of other
retroviruses reveals a larger number of genes and a much more
complex organization. HIV-1 contains, in addition to the usual
Viral
Entry
P.444
HIV-1 can also infect cells such as fibroblasts and certain brain
cells that lack the CD4 surface molecule, apparently because the
fusion-inducing activity of the transmembrane protein is
sufficient in these cases to promote entry. An additional aspect
of fusion activity is that infected cells expressing viral
glycoproteins in their membranes readily fuse with uninfected
CD4+ T lymphocytes to form large syncytia. This process appears
to provide a means for cell-to-cell transmission of the virus that
bypasses the usual extracellular phase and also damages the
membrane of uninfected cells and affects their viability.
Viral
RNA
Replication
Unique
Feature
of
the
Lentiviruses
Figure 40-3. HIV life cycle and its inhibition. The nucleoside
analogs exert their effect on HIV replication at the reverse
transcription stagethat is, after the virus has entered the host
cell genome. The affinity of HIV-reverse transcriptase for
nucleoside analogs is greater than that for the endogenous
substrates; the triphosphate form of the analogs preferentially
attaches to a nucleotide-binding site of the enzyme,
competitively inhibiting binding of the endogenous 5triphosphate molecule. The protease inhibitors block cleavage of
Two of the regulatory proteins, TAT and REV, play a positive role
in promoting viral gene expression. The TAT protein increases
the rate of viral mRNA synthesis, and REV promotes the
transport of full-length mRNA
spliced. The combined action
to promote the production of
promotes virus production at
HIV
Latency
REV
Increases transport of unspliced mRNAs.
HTLV rex
REX
Same as for REV.
HIV nef
NEF
Negative regulator of transcription.
HIV vif
VIF
Facilitates virus maturation during budding.
Gene
Protein
Function
More
Common
T-cell
leukemia
Common
Tropical
spastic
Children
paraparesis
Adults
Transformation
by
Retroviruses
Choice
Chemotherapy
Second
for
malignancy
Choice
Antiretroviral
agents
(investigational
only)
Adults
BOX 40-2 Treatment of Oncovirus (HTLV) Infection
The second mechanism is called insertional mutagenesis.
Integration of a retrovirus near particular cellular genes can
cause inappropriate expression of the gene, resulting in
uncontrolled cell growth. These cellular genes are called
proto-oncogenes, and insertional activation by the virus
is apparently caused by the close proximity of the integrated
viral promoter or enhancer to the gene. Cancers that are caused
by this mechanism have very long latent periods because
integration is random and only rarely occurs near a cellular
proto-oncogene. No human cancers are known to be caused by
this mechanism.
The causative agent of adult T-cell leukemia, HTLV-1, exemplifies
the third mechanism. In this case, the integrated provirus in the
leukemic cells from any one patient is found at a unique location
on a particular chromosome. Thus the tumors are probably
monoclonal. However, the cancer is not the result of insertional
Measures
Precautions
ONCOVIRUSES
Clinical
(HTLV-1)
Findings
irritation
also
develop.
Treatment
&
Control
comments.
REFERENCES
Levy JA: Pathogenesis of human immunodeficiency virus
infection. Microbiol Rev 1993;57:183. (Detailed review of the
mechanisms involved in the initiation and all stages of HIV
infection.).
Rosenblatt JD: Human T-lymphotropic virus types I and II.
West J Med 1993;158:379. (Molecular analogies to HIV
explained.)
2001
McGraw-Hill
41
Poxviruses
Lawrence W. Drew MD, PhD
Essentials
of
Diagnosis
inclusions
in
General
Considerations
Epidemiology
Molluscum contagiosum infection is spread through direct
person-to-person contact or through sharing of common
towels etc. The agents of the zoonotic poxvirus diseases
spread by direct contact.
Microbiology
Poxviruses are the largest of all viruses, measuring 230 by
300 nm, and are ovoid to brick shaped. They have a capsid
that is referred to as complex because it has neither helical
nor icosahedral symmetry. An outer membrane and
envelope enclose the core and core membrane. The viral
genome is a single strand of large, linear, double-stranded
DNA (molecular weight approximately 100 106 100
2006 ).
Replication of poxviruses is unique among DNA-containing
viruses, because the entire multiplication cycle takes place
within the host cell cytoplasm. Viral penetration occurs
within phagocytic vacuoles. Uncoating of the outer
membrane occurs in the vacuole. Early gene transcription
occurs within the viral core. Among the early proteins
produced is an uncoating protein that removes the core
membrane, liberating viral DNA into the cell cytoplasm.
Replication of viral DNA follows in electron-dense
cytoplasmic inclusions, referred to as factories. Late viral
mRNA is translated into structural proteins, which are
glycosylated, phosphorylated, and cleaved before assembly.
Unlike other viruses, poxvirus membranes form de novo in
the cytoplasm, rather than as part of a host cell membrane
that is picked up during a budding process. About 10,000
viral particles are produced per infected cell.
Pathogenesis
The pathologic hallmark of poxviruses is cell proliferation,
manifested by the skin lesions that give this family of
viruses its name. Most of the viruses of current human
CLINICAL
SYNDROMES
MOLLUSCUM
Clinical
CONTAGIOSUM
Findings
Smallpox
Humans
Extinct
(now
extinct)
Vaccinia
Vaccination
complications
Vaccine
Research
laboratories
Molluscum
contagiosum
Many skin lesions
Humans
Worldwide
Orf
Localized lesion
Zoonosis: sheep,
Worldwide
Cowpox
goats
Localized lesion
Zoonosis: cows
Europe
Pseudocowpox
Milker's nodule
Zoonosis: dairy cows
Worldwide
Monkeypox
Generalized
disease
Zoonosis: monkeys, squirrels
Africa
Virus
Disease
Source
Location
Table
P.449
ZOONOTIC
POXVIRUSES
Clinical
Findings
no
complications.
2. PSEUDOCOWPOX
NODULES
Clinical
OR
MILKER'S
Findings
More Common
Lesions on exposed epithelial surfaces
Genital lesions, may be generalized in AIDS patients
Less Common
Children
Adults
3.
MONKEYPOX
for
transmission.
Treatment
Molluscum
Contagiosum. Treatment of molluscum
contagiosum, if lesions are extensive or cosmetically disfiguring,
is curettage, forceps removal of central core, or application of
liquid nitrogen or iodine solutions (Box 41-2 ).
First Choice
No systemic treatment
No systemic treatment
Second Choice
Pediatric
Considerations
Rx rarely necessary
Children
Adults
Prevention
&
Control
Molluscum
Contagiosum. Prevention of molluscum
contagiosum consists of avoiding direct or indirect contact with
individuals exhibiting characteristic skin lesions (Box 41-3 ).
Zoonotic
Poxviruses. The zoonotic poxviruses can be avoided
by avoiding contact with animals exhibiting skin lesions,
especially when the human has potentially infected cuts or
abrasions.
Prophylactic
Measures
In adults, may be sexually transmitted and safe sex
may decrease spread. Direct contact with lesions should be
avoided.
Isolation
Precautions
None required
BOX 41-3 Control of Molluscum Contagiosum Infection
REFERENCES
Baxby D, Bennett M, Getty B: Human cowpox 196993: a
review based on 54 cases. Br J Dermatol 1994;131:598.
2001
McGraw-Hill
42
Parvoviruses
Lawrence W. Drew MD, PhD
Essentials
of
Diagnosis
General
Considerations
ERYTHEMA
Clinical
INFECTIOSUM
Findings
including
P.452
those with human immunodeficiency viral infection who
cannot control viral replication.
Children
Adults
More
Common
Erythema
infectiosum
Febrile
arthritis
Less
Common
Fetal infection
Stillbirth
Aplastic
APLASTIC
Clinical
crisis
CRISIS
Findings
Other
Complications
Diagnosis
B19 virus is not recovered in tissue culture but can be directly
detected in serum or throat washes during the prodromal period
or aplastic crisis by enzyme and radioimmunoassay, nucleic acid
hybridization, and immune electron microscopy. PCR is a very
sensitive method for detecting B19 but may remain positive for
months after B19 infection. The presence of characteristic
giant pronormoblasts in bone marrow may provide a
clue to parvovirus as the cause of an aplastic crisis.
More readily available and applicable to patients with erythema
infectiosum and aplastic crisis is the virus-specific IgM test,
which indicates current or recent infection. This test is not
useful in AIDS patients because they do not mount an IgM
antibody response.
Prophylactic
Measures
Isolation
Precautions
Respiratory
Treatment
No specific antiviral treatment is known, but chronic B19induced anemia may be treatable with immune globulin.
Prognosis
B19 infection can be chronic in immunocompromised patients,
with intermittent worsening of anemia for months to years.
Prevention
&
Control
REFERENCES
Cassinotti P et al: Association between human parvovirus
B19 infection and arthritis. Ann Rheumat Dis 1995;54: 498.
Frickhofen N, Abkowitz
parvovirus infection in
immunodeficiency virus
anemia in AIDS. Ann
2001
McGraw-Hill
43
Viral Infection of the Central
Nervous System
Lawrence W. Drew MD, PhD
Many viruses causing infection of the central nervous system
(CNS) are covered in chapters devoted to each type of virus.
For example, enteroviruses, the agents most frequently causing
meningitis and occasionally encephalitis, are covered in Chapter
2 7 . The herpes viruses that cause meningitis, encephalitis, or
both, especially herpes simplex virus (HSV), varicella-zoster
virus (VZV), and Epstein-Barr virus (EBV), are discussed in
Chapter 33 . This chapter considers viruses that cause CNS
diseases (Box 43-1 ) as their primary manifestations.
ARTHROPOD-BORNE
ENCEPHALITIS
Essentials
of
VIRAL
Diagnosis
rash
suggests
enterovirus
disease.
General
Considerations
macrophages,
and
monocytes.
TOGAVIRUSES
Vector
Hosts
Distribution
Disease
More Frequent
WEE, EEE, CE
SLE
Less Frequent
SLE
WEE, EEE, VEE, West Nile Virus
Rare
Progressive multifocal leukoencephalopathy,
rabies
Progressive
multifocal
disease, rabies
Children
leukoencephalopathy
Creutzfeldt-Jakob
Adults
Clinical
Findings
Differential
Diagnosis
years.
Complications
In infants < 1 year old with encephalitis, death may occur in up
to 20% and neurologic sequelae in > 50% of survivors. The
rates of these complications are less in older children and
adults.
Treatment
No treatments exist for arbovirus diseases other than supportive
care.
Prognosis
Attack rates for encephalitis are approximately 1 per 1000
infections. In older children and adults,
P.456
95% recover from encephalitis, and sequelae are
uncommon, but in infants there is high mortality and frequent
residua in survivors.
Prevention
&
Control
LYMPHOCYTIC
(LCM)
CHORIOMENINGITIS
Epidemiology
LCM virus infects hamsters and mice; chronic infection is
common in these animals and leads to chronic viremia and virus
shedding in saliva, urine, and feces. Infection of humans may
occur by way of aerosols, contamination of food, or fomites.
Bites are not a usual mechanism of spread. Persistently infected
rodents do not usually exhibit illness. The incubation period for
LCM infections averages 1014 days.
Microbiology
Arenaviruses are pleomorphic and enveloped with lipid; the
virion has a mean diameter of 120 nm. They contain twostranded RNA in a linear or circular configuration. The total
molecular weight of this RNA is 3.2 106 daltons4.8
1 06 daltons.
Pathogenesis
Arenaviruses are able to infect macrophages and possibly cause
the release of mediators of cell and vascular damage. In certain
Measures
Precautions
None
BOX 43-2 Control of Arthropodborne Viral
Encephalitis
Clinical
Syndrome
Laboratory
Diagnosis
Treatment
&
Prevention
RABIES
Essentials
of
Diagnosis
and
General
Considerations
Rabies is an acute fatal viral illness of the CNS. It can affect all
mammals and is transmitted between them by infected
secretions, most often by bite. It was first recognized more than
3000 years ago and has been among the most feared of
infectious diseases. It is said that Aristotle recognized that
rabies could be spread by a rabid dog.
Epidemiology
Rabies exists in two epizooic forms: the urban form is
associated with unimmunized
P.457
Clinical
Findings
swallowing
the mouth.
contractions
pharyngeal,
bodies;
P.458
Differential
Diagnosis
Complications
Pneumonia and other infectious complications of intensive care
are almost invariable. Respiratory paralysis results from
infection of the respiratory center.
Treatment
In the late 1800s Pasteur, noting the long incubation period of
rabies, suggested that a vaccine to induce an immune response
before the development of disease might be useful in
prevention. He apparently successfully vaccinated Joseph
Meister, a boy severely bitten and exposed to rabies, with
multiple injections of a crude vaccine made from dried spinal
cords of rabies-infected rabbits. This treatment emerged as one
of the most noteworthy accomplishments in the annals of
medicine (Box 43-3 and Prevention & Control section below for
more information).
Prognosis
Of patients with rabies, > 90% die owing to complications of the
illness or progressive
respiratory
paralysis.
Prevention
&
neurologic
dysfunction,
especially
Control
and
postexposure
prophylaxis.
First Choice
Treatment consists of immune enhancement: immune globulin
and vaccine (see Box 43-5 for dosages)
Treatment consists of immune enhancement: immune globulin
and vaccine (see Box 43-5 for dosages)
Children
Adults
Preexposure
prophylaxis. This type of prophylaxis is
recommended for individuals at high risk of contact with
rabies virus, such as veterinarians, spelunkers, laboratory
workers, and animal handlers. The vaccine currently used in
the United States for preexposure prophylaxis uses an
attenuated rabies virus grown in human diploid cell culture
and inactivated with beta-propriolactone. Preexposure
prophylaxis consists of two subcutaneous injections of
vaccine given 1 month apart, followed by a booster dose
several months later.
Postexposure
prophylaxis. This type of prophylaxis
requires careful evaluation and judgment. Every year more
prophylaxis
consists
of
immediate,
thorough
NIPAH
VIRUS
related
P.459
Measures
Precautions
PROGRESSIVE
MULTIFOCAL
LEUKOENCEPHALOPATHY
Essentials
of
Diagnosis
General
Considerations
Epidemiology
Progressive multifocal leukoencephalopathy (PML) is a rare
syndrome that occurs in immunocompromised patients,
including those with AIDS, and is caused by a papovavirus
known as JC virus (JCV). The virus was first recovered by
coculturing of brain tissue from a patient with progressive
multifocal leukoencephalopathy and Hodgkin's disease.
Polyomavirus infections are ubiquitous, and most humans
are infected with JCV by the age of 15 years.
Microbiology
The polyomaviruses are small (44 nm in diameter),
icosahedral, and lack an envelope. The double-stranded DNA
is a circular, supercoiled molecule.
Pathogenesis
Respiratory transmission is the probable mode of spread.
Immune suppression after organ transplantation or during
pregnancy is capable of reactivating latent infections.
Clinical
Findings
Differential
Diagnosis
Complications
There is progressive worsening of cerebral and neurologic
function with death usually occurring 36 months from onset.
Treatment
No specific treatment is available, but some stabilization or
improvement may occur if the immunosuppression can be
reduced, eg, control of HIV infection.
Prognosis
Rarely there may be regression of symptoms especially if
immunosuppression can be reduced. Otherwise the disease is
fatal and may be especially rapid in AIDS patients.
Prevention
&
Control
DISEASES CAUSED
UNCONVENTIONAL
BY
AGENTS
CREUTZFELDT-JAKOB
Essentials
of
Diagnosis
DISEASE
General
Considerations
Clinical
Findings
brain
Differential
atrophy.
Diagnosis
Treatment
There is no effective therapy of Creutzfeldt-Jakob disease, and
all cases have been fatal.
Prevention
The small risk of nosocomial infection is related only to direct
KURU
Kuru was a subacute, progressive neurologic disease of the Fore
people of the Eastern Highlands of New Guinea. In the local
Fore dialect, kuru means to tremble with fear or to be afraid.
The disease was brought to the attention of the western world
by Gadjusek and Zigas in the mid-1950s. Although the illness
was localized and decreasing in incidence, its study has thrown
light on the infectious nature of similar transmissible
encephalopathies. Epidemiologic studies indicated that kuru
usually afflicted adult women or children of either sex. The
disease was rarely observed outside of the Fore region, and
outsiders in the region did not contract the disease. The
symptoms and signs were ataxia, hyperreflexia, and spasticity,
which led to progressive starvation and death. Mental alertness
was unaffected until the late stages of illness.
Pathologic examination revealed changes only in the CNS, with
diffuse neuronal degeneration and spongiform changes of the
cerebral cortex and basal ganglia. No inflammatory response
was noted. Inoculation of infectious brain tissue into primates
produced a disease that caused similar neurologic symptoms
and pathologic manifestations after an incubation period of
approximately 40 months.
REFERENCES
Adams DH. Does the infective agent of scrapie replicate
without nucleic acid? An assessment. Med Hypoth
1991;35:253. (A review of the biology of prions, especially
the scrapie agent.)
Calisher CH: Medically important arboviruses of the United
States and Canada. Clin Microbiol Rev 1994;7:89.
Cantor SB et al: A decision-analytic approach to post
exposure rabies prophylaxis. Am J Publ Health 1994;84:
1144.
Centers for Disease Control and Prevention: Inactivated
Japanese encephalitis virus vaccine: recommendations of the
Advisory Committee on Immunization Practices (ACIP).
Morbid Mortal Weekly Rep 1993;42:1.
Centers for Disease Control and Prevention: Human rabies:
Alabama, Tennessee, and Texas, 1994. Morbid Mortal Weekly
Rep 1995;44:269.
Centers for Disease Control and Prevention: Compendium of
animal rabies control, 1995. Morbid Mortal Weekly Rep
1995;44:1.
Fishbein DB, Robinson LE: Rabies. N Engl J Med
1993;329:1632. (Epidemiology of rabies.)
P.462
Jahrling PB, Peters CJ: Lymphocytic choriomeningitis virus: a
neglected pathogen of man. Arch Pathol Lab Med
1992;116:486.
(Editorial
review.)
Krebs JW, Strine TW, Smith JS, Rupprecht CE, Childs JE:
Rabies surveillance in the United States during 1993. J Am
Vet Med Assoc 1994;205:1695.
Lantos PL: From slow virus to prion: a review of
transmissible
spongiform
encephalopathies. Histopathology
1992; 20:1. (A review of spongiform encephalopathies, three
of which occur in humans [Creutzfeldt-Jakob disease,
Gerstmann-Straussler-Scheinker disease, and kuru].)
Major EO, Amemiya K, Tornatore CS, Houff SA, Berger JR:
Pathogenesis and molecular biology of progressive multifocal
leukoencephalopathy, the JC virus-induced demyelinating
disease of the human brain. Clin Microbiol Rev 1992;5:49.
Prusiner SB. Transgenetic investigations of prion diseases of
humans and animals. Bio Sci 1993;339(1288):239. (A review
of the biology of prion disease.)
Rupprecht CE, Smith JS: Raccoon rabies: the re-emergence
of an epizootic in a densely populated area. Semin Virol
1994;5:155.
Weber T, Turner RW, Frye S, et al: Progressive multifocal
leukoencephalopathy diagnosed by amplification of JC virus-
2001
McGraw-Hill
Systemic
Viral
Syndromes
44
Miscellaneous
Systemic
Viral
Syndrom
This chapter includes a variety of viral infections that produce severe system
(Table 44-1 ). In some cases, these infections are transmitted by arthropod
they are acquired by direct contact with the reservoir animal or its excreta.
be hemorrhagic fever (eg, dengue, Marburg, Ebola, or Lassa fevers), genera
fever or Colorado tick fever), or pneumonia (caused by hantavirus infection).
these are endemic in the United States, hantavirus infection and Colorado tic
these viruses are RNA viruses, and vaccine has been developed for one (yel
Considerations
Dengue and yellow fever are both caused by flaviviruses, and each is spread
vector. The etiologic agents of dengue are the dengue virus types 14, wh
is caused by the yellow fever virus. Flaviviruses produce a wide range of di
hemorrhagic fevers, arthritis, encephalitis, and hepatitis. Hepatitis C is cause
and is discussed in Chapter 40 . Until recently the flaviviruses were included
family, but differences in size, morphology, gene sequence, and replication
made it necessary to classify them as an independent virus family.
Epidemiology
animals. These viruses have a very broad host range, including vertebra
birds, amphibians, and reptiles) and invertebrates (eg, mosquitoes and
Africa. Dengue is the most prevalent flavivirus and causes 100 mil
infections/year. In the past, dengue occurred in outbreaks within the Un
the presence of A aegypti and A albopictus , another potential vector, in
southern United States means that future outbreaks could occur.
Microbiology
The flaviviruses are spherical (4060 nm) enveloped, positive, singleribonucleic acid (RNA) viruses. They attach to specific receptors expresse
different cell types from many different species. Flaviviruses can also atta
receptors on macrophages, monocytes, and other cells when they are co
antibody. The antibody actually enhances the infectivity of these viruses
receptors for the virus and by promoting its uptake into these target cel
aegypti (V)
Rift Valley
Cattle, sheep (R) Aedes , others (V)
Rift Valley fever
South Africasheep Egypt-Aswan Dam Mauritania-Senegal R. Dam
Mosquito bite
1
Hantaviruses:
Sin Nombre
Deer mouse (R)
Hantavirus pulmonary syndrome
Southwestern United States
Inhalation of dried rodent excreta
1050
Nairoviruses:
Congo
Hares, hedgehogs, ticks (V)
Congo-Crimean hemorrhagic fever
Western Russia, Balkans, East Africa
Tick bites plus person-to-person (blood)
2050
Filoviridae
Marburg
Unknown
Marburg virus disease
Germany, Yugoslavialab workers:
Person-to-person (body fluids)
2025
Ebola
Unknown
Ebola hemorrhagic
fever
South
Africa;
Kenya
Sudan Zaire
Person-to-person
7090
(body
fluids)
Reoviridae
Coltvirus
Mammals (squirrels, chipmunks, rabbits, deer); tick (D andersoni )
Colorado tick fever
Western United States and Canada
Tick bite
<1
Family
Table
Agent
Reservoir/Vector
Disease
Outbreak
Locations
Route
Transmi
Pathogenesis
The flavivirus can cause lytic or persistent infections of both vertebrate
hosts. Infections of invertebrates are usually persistent, with continued
and no damage to the insect.
Female mosquitoes acquire the flaviviruses on taking a blood meal from
vertebrate host.
spreads through
salivary glands.
these cells. The
The initial viremia, after replication of the virus in these tissues, produc
symptoms such as fever, chills, headaches, backaches, and flulike sympt
days of infection. Some of these symptoms can be attributed to the inte
after infection of these target cells. Most yellow fever infections do not
this point, but secondary multiplication of virus occurs in liver, spleen, k
the common antigens expressed on all members of the viral family. One
may be occurring in the Far East, where Japanese encephalitis but not y
endemic despite the presence of the A aegypti mosquito vector for yellow
Clinical
Findings
fever. After 12 days of fever and rash, the patient's high temper
normal, only to recur 34 days later. The recurrence of fever is followe
rash that involves face, trunk and limbs but not palms or soles. The feve
second rash develops.
Between the two febrile periods the patient remains symptomatic with g
yellow fever virus are subclinical or anicteric. Icteric yellow fever infectio
characterized by severe systemic disease, with failure of the liver, kidney
hemorrhage of blood vessels. Liver involvement leads to the jaundice fro
disease obtains
P.466
its name, but massive gastrointestinal hemorrhages (so-called black
also occur.
Diagnosis
chain reaction [PCR] assay) in blood or tissue can also prove the diagnosis.
Laboratory
Findings
Flaviviruses can be grown in both vertebrate and mosquito cell lines but are
Treatment
No treatment exists for flavivirus diseases other than supportive care.
Prognosis
The fatality rate from DHF is up to 15% as a result of multiple organ failure
rate from yellow fever is approximately 10% and also results from multiple
(liver, kidney, and heart).
Prevention
&
Control
The yellow fever vaccine is attenuated from the 17D strain isolated from a p
passaged extensively in monkeys, mosquitoes, embryonic tissue culture, an
eggs. The vaccine elicits lifelong immunity to yellow fever and possibly othe
flaviviruses. Vaccines against dengue virus are also being developed.
Considerations
Two unique RNA viruses, the Marburg and Ebola viruses, are members of a n
as filoviruses. These agents can cause severe or fatal hemorrhagic fevers an
Africa. Laboratory workers have been exposed to the Marburg agent while w
cultures from African green monkeys. Travelers in or residents of central Afr
the Sudan) may be infected by the Ebola virus.
Epidemiology
Marburg virus infection was first detected among laboratory workers in
who had been exposed to tissues from apparently healthy African green
However, it is not clear that these monkeys were, or are, the reservoir f
because inoculation of Marburg virus into these monkeys produces death
carrier state. Rare cases of Marburg virus infection have been reported i
Kenya.
Ebola virus has caused disease only in Zaire and the Sudan. In rural are
Africa, 18% of the population have antibody to this virus, suggest
infections do occur. The source of the virus and means of transmission a
Clinical
Findings
Signs and Symptoms. Illness usually begins with flulike symptoms such
myalgia. Within a few days, nausea, vomiting, and diarrhea occur; a rash
develop. Subsequently, there is hemorrhage from multiple sites and dea
Laboratory
thrombocytopenia.
Diagnosis
Direct
Examination. Direct fluorescent-antibody (FA) assay can detect
tissues; virions can be seen by electron microscopy in serum or liver tis
Culture
P.467
virus may grow rapidly in tissue cultures (Vero cells), although Ebola vir
require animal (eg, guinea pig) inoculation. All specimens for filovirus di
handled with extreme care to prevent accidental infection.
Serology
Treatment
No treatment is known.
Prognosis
The mortality rate in patients with symptomatic Marburg or Ebola virus infec
Prevention
&
Control
HANTAVIRUSES
Essentials
of
Diagnosis
by
serology.
General
Considerations
Hantaviruses are members of the bunyavirus group, which is the largest fam
Clinical
Findings
Laboratory
Findings. There are no specific laboratory abnormalities, b
hemoconcentration (due to vascular leak) leukocytosis, possibly with left
increased lymphocytes, thrombocytopenia, or prolonged PTT are seen in
cases. In addition, there is evidence of progressively worsening lung fun
Imaging
Differential
Diagnosis. Acute, severe pneumonia of multiple causes mu
distinguished from HPS. In particular, pneumonia caused by influenza A
spp., Chlamydia
pneumoniae , or Pneumocystis
carinii may be similar, bu
epidemiology, age of the patient, and other factors provide clues to the
Complications
Diagnosis
Culture
Virus may be recovered by inoculation of animals or by cell culture.
IgM-specific assays are the main method to rapidly document acute infe
Seroconversion or a fourfold increase in IgG antibody is useful to docum
infection, but cross-reactions within viral genera are common.
Treatment
Ribavirin has been used to treat hantavirus pulmonary syndrome, but its effi
established. Supportive therapy of ARDS is critical to survival.
Prognosis
HPS is fatal in approximately 50% of those who develop clinical illness.
Prevention
&
Control
COLORADO
TICK
FEVER
saliva when they feed on a new host. Many ticks have been shown to be
D andersoni is the predominant vector and the only proven source of hu
Natural hosts can be one of many mammals, including squirrels, chipmu
deer. Exposure to ticks is the major risk factor. Human disease is report
spring, summer, and fall months. Colorado tick fever is not contagious b
transmitted by blood transfusion.
Microbiology
The viral life cycle includes vertebrates, secondary hosts, and invertebra
Replication occurs in the cytoplasm of various cells of insect and mamm
Colorado tick fever virus infects hematopoietic cells without severely da
Viremia therefore can persist for weeks or months even after symptoma
Clinical
Findings
Laboratory
Findings. A leukopenia involving both neutrophils and lymp
important hallmark of the disease. Leukocyte counts are generally less t
with a relative lymphocytosis. Despite these findings, disease in children
relatively mild, and uncomplicated recovery can be expected.
Imaging
None
reported.
Differential
Diagnosis. Colorado tick fever must be differentiated from
spotted fever, a tick-borne bacterial infection characterized by extensive
systemic illness.
Complications
There are no serious complications.
Diagnosis
P.469
very recent infection. A sharp decline in IgM antibody occurs ~45 days a
illness.
Treatment
Prognosis
Recovery occurs in > 99% of cases.
Prevention
&
Control
Lassa fever, with its focus of endemicity in West Africa, is the best known o
hemorrhagic fevers. Other agents, such as Junin and Machupo, cause similar
different geographic areas (Argentina and Bolivia, respectively). Lymphocyt
virus (LCM) is an arenavirus that causes viral meningitis (see Chapter 43 ).
Epidemiology
Each arenavirus infects specific rodents; for example, the natural host of
is a small Nigerian rodent. Chronic infection is common in these animals
chronic viremia and virus shedding in saliva, urine, and feces. Infection o
primarily from droppings and may occur by way of aerosols, contaminatio
fomites. Bites are not a usual mechanism of spread. Persistently infected
usually exhibit illness. Human-to-human infection occurs with Lassa feve
contact with infected secretions or body fluids, but this mode of spread r
Arenaviruses are able to infect macrophages and possibly cause the rele
of cell and vascular damage. In certain laboratory animals the clinical se
arenavirus disease appears to be directly related to the host's immunolo
greater the immune (especially T lymphocyte) response, the worse the
these mechanisms are operative in human infection is not clear. In patie
hemorrhagic fever, petechiae and visceral hemorrhage occur, as do liver
necrosis, but not vasculitis.
Clinical
Findings
Diagnosis
present for laboratory workers handling body fluids. Therefore, if the diagno
laboratory personnel should be warned and specimens processed only in fa
for the isolation of contagious pathogens.
Treatment
Prevention
&
Control
REFERENCES
Ramirez-Ronda CH: Dengue in the Western Hemisphere. Infect Dis Clin Nor
1994;8:107. (Describes disease and epidemiology.)
2001
McGraw-Hill
45
Papovaviruses
Lawrence W. Drew MD, PhD
PAPILLOMAVIRUSES
Essentials
of
Diagnosis
General
Considerations
Epidemiology
Papillomaviruses (HPVs) cause skin warts, most commonly
CLINICAL
SKIN
SYNDROMES
WARTS
There are two main types of skin warts: flat, or superficial, and
plantar, or deep growths. Most persons are infected with the
common HPV types (1 through 4), which infect keratinized
surfaces, usually on the hands and feet, and occur frequently in
childhood or early adolescence. They regress spontaneously if
given time.
ANOGENITAL
WARTS
CERVICAL
DYSPLASIA
&
NEOPLASIA
BOX
45-1
Papillomavirus
Children
More
Skin warts
Common
Infection
Adults
Anogenital
warts
(condyloma
accuminata)
Cervical infection,
dysplasia
Less
Laryngeal
Cervical
Common
papillomas
Laryngeal
carcinoma
papillomas
Diagnosis
A wart can be confirmed microscopically by its characteristic
histologic appearance, consisting of hyperplasia of prickle cells
and the production of excess keratin (hyperkeratosis). HPV
infection is suggested by the presence of koilocytotic
(vacuolated) squamous epithelial cells that are rounded and
occur in clumps. HPV virions can be seen by electron microscopy
in lesions as can HPV antigens by immunofluorescent and
immunoperoxidase techniques. Use of molecular probes to
detect HPV DNA is the method of choice for establishing the
presence of HPV genomes in cervical swabs and in tissue. HPVs
do not grow in cell cultures, and tests for HPV antibodies are
rarely used except in epidemiologic surveys.
Treatment
Spontaneous disappearance of warts is the rule, but because
this may take many months to years, intervention is sometimes
Children
First
Choice
Second
Choice
Pediatric
Adults
Spontaneous
regression
Spontaneous
regression
Electrocautery,
cryotherapy, or
chemical means
Same
Podophylline
Considerations
Prevention
&
Control
POLYOMAVIRUSES
Essentials
of
Diagnosis
General
Considerations
Epidemiology
There are two important human
P.473
papovaviruses: BK and JC viruses. SV40 is a simian
polyomavirus that may be present in monkey kidney
cultures and did contaminate certain lots of oral poliovirus
vaccine (see below). The most important disease caused by
a papovavirus is progressive
(PML) (see Chapter 43) .
multifocal
leukoencephalopathy
Prophylactic
Measures
Isolation
Vaccines
being
evaluated
Precautions
CLINICAL
SYNDROMES
Children
More
Common
Asymptomatic
infection
Less
Common
Cystitis
Adults
Asymptomatic
infection
Diagnosis
Cytologic examination of urine is the simplest method for
documenting active polyomavirus infection. Virus may be
demonstrated in tissue or cells by immunofluorescent,
immunoperoxidase, or DNA hybridization techniques, and biopsy
of brain has been the definitive method for diagnosing PML.
Polymerase chain reaction analysis of cerebrospinal fluid is
replacing biopsy as a noninvasive procedure for diagnosing JCV
infection of the CNS. Culturing of polyomaviruses can be
performed but requires specialized cells and may take weeks to
months. Serology is not useful to diagnose PML because serum
antibody is common in the general population.
Treatment
No treatment is established for BKV or JCV infection. PML has
been treated with numerous different antiviral agents, and there
have been conflicting results, especially with cytosine
arabinoside. Spontaneous remission may occur, and diminishing
immunosuppression may be beneficial.
Prevention
&
Control
REFERENCES
Bauer HM et al: Genital human papillomavirus infection in
female university students as determined by a PCR-based
method. JAMA 1991;265:472.
Holman RC et al: Epidemiology of progressive multifocal
leukoencephalopathy in the United States: Analysis of
national mortality and AIDS surveillance data. Neurology
1991;41:1733.
Koutsky LA et al: A cohort study of the risk of cervical
intraepithelial neoplasia grade 2 or 3 in relation to
papillomavirus infection. N Engl J Med 1992;327:1272.
Markowitz RB et al: Incidence of BK virus and JC virus
viruria in human immunodeficiency virus-infected and
uninfected subjects. J Infect Dis 1993;167:13.
2001
McGraw-Hill
46
Staphylococci
Karen Bloch MD, MPH
STAPHYLOCOCCUS
Essentials
of
AUREUS
Diagnosis
in
grapelike
bunches
Biochemically differentiated
of the enzyme catalase.
microscopically.
from
streptococci
by
presence
staphylococci
by
General
Considerations
Epidemiology. Staphylococcus
aureus colonizes the human
skin, vagina, nasopharynx, and gastrointestinal tract.
Colonization occurs shortly after birth and may be either
transient or persistent. Published studies differ widely in
estimates of the prevalence of S aureus carriage. Between
10% and 35% of healthy adults have transient or persistent
nasopharyngeal colonization. This percentage is increased
among health care workers and individuals with repetitive
needle exposure such as diabetics, patients on hemodialysis,
and injection drug users. Vaginal carriage in premenopausal
women approaches 10%, with the highest prevalence rates
found at the start of the menstrual cycle.
Phage typing and molecular techniques have demonstrated
that invasive disease is usually caused by the colonizing
strain; therefore it is not surprising that groups with the
highest prevalence of colonization are at the highest risk for
S aureus infection. Fortunately, progression to infection is
relatively unusual, occurring in only 2.5% of colonized
nursing home patients and 37% of postoperative patients
(compared with 11% of noncolonized postsurgical patients).
Acute infections in noncolonized patients are usually
attributed to physical contact with a colonized individual.
Studies have proven that health care workers can serve as
vectors for transmission of staphylococci. The importance of
person-to-person transmission underscores the need for
strict hand washing in hospital settings. Other, less
common, methods of acquisition include airborne
transmission and spread from clothing and bed linens.
Microbiology. Staphylococci are aerobic, nonmotile, grampositive cocci frequently cultured from environmental and
clinical specimens. Although these organisms are generally
considered commensal (ie, nonpathogenic normal flora)
when cultured from the skin, nasopharynx, intestinal tract,
and vagina, they may at times cause life-threatening
Capsule
Impairs
opsonization
and
phagocytosis
+++++
+
Catalase
Degrades H2 O2 to H2 O + O2
Prevents PMN3 respiratory burst
++++
++++
Coagulase
Catalyzes conversion of fibrinogen to fibrin
Fibrin matrix inhibits phagocyte migration
Promotes abscess formation
++++
0
Inducible
Beta-Lactamase
Intrinsic
Beta-Lactam
Resistance
Toxins
Exfoliation
+
0
TSST-1
Toxic shock syndrome
+
0
Enterotoxins
Nausea/vomiting
+
0
Biofilm
Production
Mucoid strains
3 PMN: Polymorphonuclear cell
Factor
Table
Action or Associated
Syndrome
S aureus
(%) 1
CoNS
(%) 1
needle
exposure
Insulindependent
diabetics
Injection drug users
Hemodialysis
patients
Increased
colonization
Breaks in skin integrity
Qualitative
PMN1 impairment
Decreased
Quantitative
phagocytosis
PMN
impairment
Post-chemotherapy
neutropenia
Congenital
neutropenia
Decreased
Impaired
phagocytosis
PMN
Job's
chemotaxis
syndrome
skin
Thermal
condition
burns
body
Prosthetic joints
Vascular access devices
Ventriculoperitoneal
shunts
Break in skin integrity (at time of insertion)
Local alteration in immunity
1
Example
Impairment
CLINICAL
SYNDROMES
PYOGENIC
Clinical
CUTANEOUS
INFECTIONS
Findings
patients
with
carbuncles.
Differential
Diagnosis. The differential diagnosis of
folliculitis includes pseudofolliculitis barbae, insect bites,
acne vulgaris, foreign body reactions, and milia. Alternative
diagnoses for furunculosis include pilonidal cysts, cystic
acne, and hidradenitis suppurativa. A carbuncle may be
confused with a furuncle, a deep-seated skin infection such
as necrotizing fasciitis, or a kerion.
Complications. These infections are generally self-limited
and do not disseminate beyond the skin. Local complications
include cellulitis and osteomyelitis of adjacent bone. There
have been anecdotal reports of facial lesions ascending
intracranially to cause septic cavernous vein thrombosis.
Bacteremia, a relatively common complication of
carbunculosis, may result in secondary infections including
endocarditis,
More
hematogenous
osteomyelitis,
Common
Folliculitis
Papules
Pustules
Furuncles
Abscesses
Scarlatiniform
eruption
Blisters eroding to honeycolored crust
Local tenderness
Regional
lymphadenopathy
Bullous impetigo
Local
erythroderma
Flaccid bullae rupturing to brown crust
Involvement of face, trunk, perineum
Less
Common
Carbuncles
and
pneumonia.
Coalescent
Fever
Systemically
abscesses
with
draining
fistulae
ill
SSS
Diffuse dermal
Nikolsky's sign
Fever
Leukocytosis
Bacteremia
1
desquamatino
Impetigo
SSSS1
Diagnosis
Pyogenic skin infections are diagnosed by clinical exam, with
culture of purulent material obtained by incision and drainage to
confirm staphylococcal infection and determine antibiotic
susceptibility patterns. Blood cultures may also guide antibiotic
therapy in patients with signs of systemic illness.
Treatment
Treatment for folliculitis and furunculosis is primarily supportive
(Box 46-2 ). Stringent attention to hygiene is key; the affected
areas should be washed at least twice daily with a mild
antibacterial soap, and overlying clothing should be loose
fitting. Furuncles either spontaneously drain or require incision
and drainage once they have matured (come to a head).
Antibiotic therapy is rarely necessary for these conditions.
Choice
hydration
Choice
Adult:
Cephalexin, 500 mg orally every 6 h for 7 days
Pediatric:
Cefazolin, 20 mg/kg/d IV every 8 h for 1014 days
Adult:
Cefazolin, 12 g IV every 8 h for 1014 days
Penicillin
Allergic
Impetigo
SSSS1
NONPYOGENIC
Clinical
SKIN
INFECTIONS
Findings
Figure
46-3.
Diffuse
epidermal
desquamation
characteristic
P.480
Diagnosis
Impetigo is diagnosed by the presence of the classic golden
crusts on physical examination; a microbiologic diagnosis is
rarely necessary. SSSS can be diagnosed by rupturing an intact
bulla and culturing the extravasated fluid for S aureus. Latex
agglutination or ELISA confirms the presence of the
staphylococcal exfoliative toxin.
Treatment
Mild cases of (nonbullous) impetigo may be treated with topical
mupiricin; however, more serious infections need oral
antibiotics (Box 46-2 ). Bullous impetigo requires treatment
with an oral antistaphylococcal agent. The high rates of
morbidity and mortality in generalized SSSS mandate
hospitalization for aggressive hydration and parenteral
antibiotics. Extensive desquamation predisposes patients to
secondary infections, and they should receive aggressive topical
care such as that given to burn victims.
TOXIC
SHOCK
SYNDROME
Clinical
Findings
1 . Temperature
>38.9C
Probable
diagnosis:
Desquamation plus 3 other major criteria
All five major criteria in the absence of desquamation
Table
Differential
Diagnosis. Other entities causing rash,
hypotension, or fever that may be confused with
staphylococcal TSS include streptococcal TSS, Rocky
Mountain spotted fever, viral infection with exanthem (such
as measles or EBV), meningococcemia, leptospirosis, the
septic shock syndrome, Kawasaki's disease, and druginduced reactions (such as erythema multiforme or toxic
epidermal necrolysis). A thorough history with particular
attention to tick exposures, ill contacts, travel, pets, and
medication use is essential in excluding the mimicking
conditions.
Complications. Case fatality rates for TSS range from 3%
to 6% and are higher for nonmenstrual disease. Digital
gangrene may occur as a result of sustained hypotension
and impaired extremity perfusion. Neuropsychiatric
symptoms such as emotional lability, impaired memory, and
decreased concentration are common sequelae in survivors.
Diagnosis
Formal criteria for the diagnosis of TSS have been developed to
facilitate surveillance and standardize case definition (Table 463 ). Increased awareness of the association between
menstruation, tampon use, and TSS has led to improved
diagnosis of menstruation-associated disease. Nonmenstrual
disease lacks unifying epidemiologic characteristics, which
makes diagnosis more difficult. Postoperative TSS is particularly
difficult to diagnose, as surgical wound inflammation may be
minimal, and early signs are nonspecific.
The diagnosis of TSS is supported by a culture of TSST-1producing S aureus from an infected focus, although this is not
a criterion for case definition. TSST-1-producing staphylococci
are isolated from the vagina in 85% of menstruation-associated
disease but are isolated from infected foci in only 4060% of
P.481
cases of nonmenstrual disease. S aureus bacteremia rarely
Treatment
Treatment requires identification and removal of foreign bodies
(such as tampons) and irrigation and dbridement of infected
wounds. Aggressive hydration and close hemodynamic
monitoring are essential in the early stages of TSS. All patients
should be treated with parenteral agents active against
staphylococci (Box 46-3 ). In vitro, clindamycin inhibits TSST-1
protein synthesis, providing at least a theoretical basis for
combination therapy with this agent and a penicillinase-resistant
penicillin.
PRIMARY BACTEREMIA
ENDOCARDITIS
&
Staphylococci
(both S aureus and CoNS) have emerged as the
two most common organisms cultured from patients with
primary bloodstream infections. The term primary
bacteremia refers to positive blood cultures without an
identifiable anatomic focus of infection. Differentiation of
primary bacteremia from infective endocarditis (IE), in which
infection of the cardiac valves leads to continuous bacterial
seeding of the bloodstream, may challenge even the most
experienced clinician. Primary S aureus bacteremia is associated
with insulin-dependent diabetes, the presence of a vascular
graft, and, most significantly, the presence of an indwelling
intravascular catheter. Risk factors for IE include structurally
abnormal valves, recent injection drug use, and the presence of
a prosthetic cardiac valve.
Supportive
Measures
Choice
Choice
Allergic
PLUS
Clinical
Findings
ranging
P.482
postoperative wound
and cellulitis. In
focus of infection,
bacteremia from
rupture of the
the earliest
systemic
bacteremia are
Common
Fever
Leukocytosis
Heart murmur (~50%)
Pleuritic chest pain
Cough
Hemoptysis
Dyspnea
Fever
Leukocytosis
Heart murmur (~85%)
Systemic emboli
Hemodynamic
compromise
Congestive
heart
failure
Uncommon
Hemodynamic
compromise
Congestive heart failure
Systemic
emboli
Osler's nodes
Janeway lesions
Splinter
hemorrhages
Roth spots
Right-sided
Left-sided
Treatment
Optimal empiric treatment for primary bloodstream infection is
based on the likelihood that an organism is resistant to
methicillin (defined as an MIC 8 g/ml). Penicillinaseresistant semisynthetic penicillins (PRSP) such as oxacillin or
nafcillin are the recommended agents for community-acquired
infections, or nosocomial infections in institutions with
documented low prevalence rates for MRSA. In facilities with
significant isolation rates for MRSA, empiric treatment with
vancomycin is indicated. A PRSP should be substituted as soon
as the bacteria is proven susceptible, as vancomycin is less
active against S aureus , and patients treated with this agent
have longer duration of fever and bacteremia. Regardless of
Native
Valve
Endocarditis
Native
Valve
Endocarditis 2
Allergy
Valve
(PVE)
(Prosthetic
Valve)
or
pulmonary emboli
3 Cephalosporins contraindicated if penicillin allergy is
immediate hyper sensitivity reaction
Scenario
Agent/Dose/Route/Duration1
Endocarditis
OSTEOMYELITIS
Clinical
Findings
Diagnosis
Because of the need for prolonged antibiotic therapy with
osteomyelitis, a concerted effort to obtain a microbiologic
diagnosis before initiating therapy should be made. Culture of
cutaneous sinus tracts has an unacceptably low sensitivity and
specificity and is not recommended for diagnostic purposes. All
patients should have a surgical bone biopsy, as this is the only
reliable way of obtaining adequate culture results to guide
therapy.
General
Care
Dbridement
Methicillin
of
devitalized
bone
Sensitive
BY
Allergic
Penicillinaseresistant,
oxacillin
semisynthetic
penicillinnafcillin
or
Adults
Treatment
The treatment of osteomyelitis presents a particular challenge
as antibiotics penetrate bone poorly; antibiotic concentrations in
bone are only 5% that of serum. All successful treatment
regimens require high dosing for prolonged durations (Box 46-6
). Standard regimens require intravenous therapy for 46
COAGULASE-NEGATIVE
STAPHYLOCOCCI
Essentials
of
Gram-positive
Diagnosis
cocci.
in
grapelike
bunches
Biochemically differentiated
of the enzyme catalase.
Biochemically differentiated
the enzyme coagulase.
microscopically.
from
streptococci
by
production
General
Considerations
BACTEREMIA
&
ENDOCARDITIS
Clinical
Findings
either
bacteremia
or
endocarditis.
Diagnosis
The diagnosis of CoNS bacteremia or endocarditis is supported
Treatment
The recommended regimens for CoNS bacteremia are given in
Box 46-7 . Although > 70% of CoNS are resistant to PRSPs,
beta-lactam resistance is heterotypically expressed, and
antibiograms may falsely suggest methicillin sensitivity.
General
Care
Regimens
Bacteremia
PV
endocarditis
URINARY
S
TRACT
INFECTIONS
Clinical
Findings
saprophyticus
Diagnosis
Definitive
diagnosis
of S
Treatment
S saprophyticus is sensitive to the antibiotics empirically used
to treat community-acquired, uncomplicated UTIs (see Chapter
1 6 ). Treatment failures of S saprophyticus UTIs have been
reported with single-day therapy (particularly with the
fluoroquinolones), leading to the current recommendation of 3
days of antibiotics, regardless of which agent is used. Of note, S
saprophyticus is variably sensitive to vancomycin, and this
agent should not be used for empiric therapy.
Nasopharyngeal
Colonization
Tract
Colonization
or
or Extensive
Involvement
Skin
Involvement/Lower
Respiratory
Prevention
&
Control
nosocomial
infections.
REFERENCES
Archer GL, Climo MW: Antimicrobial susceptibility of
coagulase-negative staphylococci.
Chemother
1994;38:2231.
Antimicrob
Agents
for
osteomyelitis.
2001
McGraw-Hill
pneumoniae
47
Streptococcus
pneumoniae
Essentials
of
Diagnosis
agglutination of CSF.
General
Considerations
found in
typically
Intermittent
adult
with the
pneumoniae.
pneumoniae are
inflammatory response
The critical factor in
ability to evoke this
More
Common
bacteremia1
Common
Empyema
Septic arthritis
Peritonitis
Endocarditis
Pericarditis
Cellulitis
Endometritis
Osteomyelitis
Brain abscess
1
More
Common
Fever
Chills
Sweats
Cough
Rusty sputum
production
Dyspnea
Fever, tachycardia, tachypnea
Consolidative findings on chest exam
Hypoxemia
Elevated
Less
leukocyte
count
Common2
status
Signs
Laboratory
Tests1
CLINICAL
SYNDROMES
PNEUMONIA
This section focuses on the clinical findings, diagnosis, and
treatment of pneumococcal pneumonia. Please see Chapters 9
and 1 0 for a general discussion of pneumonia and upper
respiratory
infection.
Clinical
Findings
often
in
persons
count
opportunistic
pathogens.
and
meningitis
Diagnosis
The diagnostic approach to pneumococcal pneumonia first
involves correctly diagnosing the syndrome of pneumonia and
second involves defining S pneumoniae as the causative agent.
Whether the setting is community acquired or nosocomial, the
diagnosis of pneumonia is made by chest radiography of patients
with suggestive predisposing factors, symptoms, and physicalexamination findings. This avoids the unnecessary costs and
medication side effects that are associated with prescribing
antibiotics to the large numbers of individuals who have viral
upper-respiratory-tract infections and who do not have
pneumonia. Although chest radiography has been dismissed by
some as being cost ineffective in the outpatient setting, this
ignores the incalculable costs of the subsequent development of
antibiotic resistance that occurs when antibiotics are
inappropriately prescribed. Thus, a chest radiograph is required
for all patients in whom pneumonia is suspected.
No constellation of presenting signs or symptoms has proven to
be adequately predictive of pneumonia caused by S pneumoniae.
Hence, once the diagnosis of pneumonia has been established on
clinical and radiographic grounds, definitive diagnosis of
pneumococcal pneumonia is based on the identification of the
organism in normally sterile fluid (see above and Table 47-1 for
microbiologic identification of S pneumoniae ). With the rare
exception of when transthoracic biopsies are performed,
Treatment
The approach to treatment of any of the syndromes caused by S
pneumoniae must be considered in two partsempiric and
definitive therapy. Empiric therapy is prescribed when a patient
presents with a clinical
P.495
syndrome (eg, pneumonia) and, as is often the case, the
causative agent has not yet been identified. Empiric therapy
must cover all the epidemiologically likely agents. Definitive
treatment is used once S pneumoniae has been identified as the
causative agent.
On presentation with a clinical syndrome compatible with
pneumonia, most patients are treated empirically with broadspectrum antibiotics (see Chapter 23 ). Assuming that a patient
is responsive to an empiric regimen that covers S pneumoniae ,
a switch to definitive therapy depends on the confidence that the
clinician and microbiology laboratory have that S pneumoniae is
the sole causative agent. As noted above, growth of S
pneumoniae in normally sterile body fluids like blood or pleural
fluid is definitive proof of pneumococcal disease. In these
instances, if other copathogens have been adequately excluded,
a switch to definitive therapy is indicated. Growth of S
pneumoniae in a culture of expectorated sputum offers
suggestive but not definitive proof because some persons may
have pneumococcal colonization without pneumococcal disease.
The isolated appearance of gram-positive lancet-shaped
diplococci on sputum Gram stain (without culture growth) is
again suggestive but is also the least definitive. Switching to
definitive therapy in these latter two patient groups is a matter
of clinical judgment and depends on several factors, including
the past
a minimal
recent 30of isolates
is
unlikely.
MENINGITIS
This section focuses on the clinical findings, diagnosis, and
treatment of pneumococcal meningitis. Please also see Chapter
5 2 for a general discussion of meningitis.
Clinical
Findings
First Choice
Penicillin V (7 mg/kg orally every 6 hmaximum 500 mg/dose)
O R Penicillin G (16, 500 U/kg IV every 4 hmaximum 1 million
U/dose)
Penicillin V (500 mg orally four times daily) O R Penicillin G (1
million U IV million every 4 h)
Amoxicillin (13.3 mg/kg orally three times daily maximum
500 mg/dose) O R Penicillin G (33,000 U/kg IV every 4 h
maximum 2 million U/dose)
Amoxicillin (500 mg orally three times daily) O R Penicillin G (2
million U IV every 4 h)
Cefpodoxime2 (5 mg/kg orally every 12 hmaximum 200
mg/dose) O R Ceftriaxone2 (25 mg/kg IV every 12 h
maximum 1 g/dose)
Cefpodoxime2 (200 mg orally twice daily) O R Ceftriaxone2 (1 g
IV every 12 h)
Second Choice
Amoxicillin (13.3 mg/kg orally three times daily maximum
500 mg/dose) O R Cefazolin (20 mg/kg IV every 8 hmaximum
1 g/dose)
Amoxicillin (500 mg orally three times daily) O R Cefazolin (1 g
IV every 8 h)
Cefuroxime axetil (15 mg/kg orally twice daily maximum 500
mg/dose) O R Cefazolin (20 mg/kg IV every 8 hmaximum 1
g/dose)
Cefuroxime axetil (500 mg orally twice daily) O R Cefazolin (1 g
IV every 8 h)
Cefotaxime2 (25 mg/kg IV every 6 hmaximum 1 g/dose)
Cefotaxime2 (1 g IV every 6 h)
Penicillin
Allergic
Erythromycin (7.5 mg/kg orally every 6 h or 5 mg/kg IV every 6
hmaximum 500 mg/dose) O R Clindamycin 4 mg/kg orally four
times daily maximum 300 mg/dose or 8.3 mg/kg IV every 8
hmaximum 300 mg/dose)
Erythromycin (500 mg orally or IV every 6 h) O R Clindamycin
(300 mg orally four times daily or 600 mg IV every 8 h)
Clindamycin (4 mg/kg orally four times daily maximum 300
mg/ dose or 8.3 mg/kg IV every 8 hmaximum 600 mg/dose)
Clindamycin (300 mg orally four times daily or 600 mg IV every
8 h)
Vancomycin (10 mg/kg IV every 6 h)
Vancomycin (1 g IV every 12 h)
1 Choices for oral and parenteral therapy are given. The use of
oral vs parenteral therapy depends on the patient's clinical
course and gastrointestinal function. All dosages assume normal
renal function.
2 Assuming in vitro susceptibility. If not susceptible to
cephalosporins, a suitable fluoroquinolone (such as sparfloxacin
or levofloxacin) or vancomycin must be used.
Susceptible
(MIC <0.1
g/mL)
Children
Adults
Intermediate
Resistance (MIC
0.11.0
g/mL)
Resistant
(MIC
2.0g/mL)
Children
Children
Adults
Highly
Adults
More
Common
Headache
Stiff neck
Fever
Chills
Sweats
Photophobia
Fever, tachycardia
Nuchal rigidity
Kernig's and Brudzinski's signs
Elevated leukocyte count
Increased intracranial pressure (>180 mm H2 O)
CSF pleocytosis (500 to 10,000 cells/mm3 , with
polymorphonuclear cell predominance)
Elevated CSF protein (100500 mg/dL)
Depressed CSF glucose (<40 mg/dL)
Less
Common2
Cough
Earache or facial pressure/ postnasal discharge
Confusion
Hypotension
Papilledema
Focal neurologic deficits
Hyperesthesia
Altered mental status
Consolidative findings on chest exam
Purulent discharge from nose or ear; bulging tympanic
membrane
Hypoxemia
1
Symptoms
Signs
Laboratory
Tests1
First
Choice
Adults
Intermediate or Highly
Resistant
(MIC0.1g/mL)
Children
Adults
Diagnosis
In patients with compatible clinical findings of meningitis, a
lumbar puncture is always indicated except when evidence on
imaging suggests a risk of herniation. Although lumbar puncture
is critical to diagnose meningitis in general and to detect S
pneumoniae specifically, delays in performing it should not delay
empiric administration of antibiotics. Blood cultures should also
be performed, and it is usually possible to collect them before
antibiotic treatment. In such cases in which antibiotics must be
given before lumbar puncture, blood cultures may serve as the
only definitive means of specific pathogen detection.
Treatment
As with pneumonia, patients presenting with acute meningitis
receive broad-spectrum empiric regimens that should include
coverage for S pneumoniae (see Chapter 52 ). Unlike
pneumonia, ascertainment of the causal pathogen is more
common in acute bacterial meningitis, thus giving the clinician
more frequent opportunities to switch to definitive therapy.
Either a characteristic CSF Gram stain or culture for S
pneumoniae is definitive proof of pneumococcal meningitis.
Antimicrobial susceptibility testing of S pneumoniae is the most
important factor in determining definitive therapy (Box 47-5 ).
Unlike the situation in
P.499
OTHER
SYNDROMES
definitive
treatments.).
Prevention
&
Control
Aged 65 y
Aged 264 y with chronic illnesses such as chronic
cardiovascular disease (coronary artery disease, congestive
heart failure, and cardiomyopathies), chronic pulmonary
disease (chronic obstructive pulmonary disease but not
isolated asthma), diabetes mellitus, alcoholism, chronic liver
disease (including cirrhosis), cerebrospinal fluid leaks, and
functional or anatomic asplenia (including sickle cell disease)
Aged 264 y living in special environment or social
settings, such as Alaskan natives and certain American
Indian populations as well as residents of nursing homes and
other long-term-care facilities
Aged 264 y who are immunocompromised, including those
with HIV infection, leukemia, lymphoma, Hodgkin's disease,
multiple myeloma, generalized malignancy, chronic renal
failure, or nephrotic syndrome; those receiving
immunosuppressive
chemotherapy
(including
corticosteroids); and those who have received an organ or
bone marrow transplant
Heptavalent conjugate vaccine is recommended for the
following persons:
Aged <2 y and high-risk children between 2 and 5 years of
age
Daily oral penicillin V is recommended for children with
functional (eg, sickle cell disease) or anatomic asplenia
Isolation
Precautions
None required
1 See text for recommendations for revaccination.
BOX 47-6 Control of Invasive Streptococcus
Infections
pneumoniae
REFERENCES
Advisory Committee on Immunization Practices: Prevention of
pneumococcal disease: recommendations of the Advisory
Committee on Immunization Practices (ACIP). Morbid Mortal
Wkly Rep 1997;46(RR-8):1. (Evidence-based review of the
epidemiology of pneumococcal disease and guidelines for the
use of the polyvalent polysaccharide vaccine.)
Advisory Committee on Immunization Practices: Preventing
pneumococcal disease among infants and young children:
recommendations of the Advisory Committee on
Immunization Practices (ACIP). Morbid Mortal Wkly Rep
2000;49(RR-9). (New recommendations on use of conjugate
vaccine.)
Afessa B, Greaves WL, Frederick WR: Pneumococcal
bacteremia in adults: a 14-year experience in an inner-city
university hospital. Clin Infect Dis 1995;21(2):345. (Review
of 304 cases of pneumococcal bacteremia from an inner-city
hospital in Washington, DC. Case-fatality rates did not
change significantly in the past six decades.)
Bartlett JG et al: Community-acquired pneumonia in adults:
guidelines for management. Clin Infect Dis 1998;26:811.
(Comprehensive guidelines on the diagnosis and management
of community-acquired pneumonia from the Infectious
Diseases Society of America. Much emphasis is provided on
the prominent role of S pneumoniae in this disease.)
Bradley JS, Scheld WM: The challenge of penicillin-resistant
Streptococcus
pneumoniae meningitis: current antibiotic
therapy in the 1990s. Clin Infect Dis 1997;24(Suppl 2):S213.
resistance
and
9.5%
showed
vaccination,
and
more
2001
McGraw-Hill
pyogenes
48
Streptococcus
pyogenes
Essentials
of
Diagnosis
fever:
migratory
arthritis,
carditis,
Syndenham's
pharyngitis.
General
Considerations
Epidemiology. Streptococcus
pyogenes is a human
pathogen without an animal reservoir. Group A streptococci
(GAS) cause most streptococcal disease, but other groups
are important pathogens in some settings (Box 48-1 ).
Group A streptococcal infections have
in children younger than age 10. The
prevalence is also higher (1520%)
with that in adults (<5%). Age is not
toxic
shock
syndrome
(strepTSS).
use
complex
biochemical
and
More
Common
Cellulitis
Erysipelas
Bacteremia
Necrotizing
fasciitis
Streptococcal toxic shock
Pharyngitis
Scarlet fever
Impetigo
Post-streptococcal
Rheumatic fever
syndrome
glomerulonephritis
Bacteremia
Less
(neonates)
Common
Pharyngitis
Scarlet fever
Impetigo (homeless)
Erysipelas
Streptococccal toxic
Necrotizing fasciitis,
Adults
BOX
48-1
shock syndrome
except after chickenpox
Children
Streptococcal
Bacterial Cell
Extracellular
Infections
Structure
Products
&
contact
cytotoxicity.
streptococcal
superantigen,
P.504
CLINICAL
SYNDROMES
PHARYNGITIS
CARRIER
Clinical
&
THE
ASYMPTOMATIC
Findings
Adults
Diagnosis
Definitive diagnosis is difficult when based only on clinical
parameters, especially in infants, among which rhinorrhea may
be the dominant manifestation. Even in older children with all of
the above physical findings, the correct clinical diagnosis is
made in only 75% of patients. Absence of any one of the classic
signs greatly reduces the specificity. Rapid antigen detection
tests in the office setting have a sensitivity and specificity of
4090%. A popular approach in clinical practice is to obtain
two throat swab samples from the posterior pharynx or tonsillar
Choice
<60 lbs:
>60 lbs:
Second
Ampicillin
require IV treatment)
Ampicillin plus clavulinic acid, 2040 mg/kg/ day, PO (may
require IV treatment)
Options for Penicillin-Allergic Patients
Clindamycin, 10 mg/kg/day, PO
Clindamycin, 10 mg/kg/day, PO
Children
Adults
SCARLET
FEVER
STREPTOCOCCAL
PYODERMA
(Impetigo
contagiosa)
Impetigo is most common in patients with poor hygiene or
malnutrition. Colonization of the unbroken skin occurs first,
then intradermal inoculation is initiated by minor abrasions,
insect bites, etc. Single or multiple thick-crusted, golden-yellow
lesions develop within 1014 days. Penicillin orally or
parenterally, or bacitracin or mupiricin topically, are effective
treatments for impetigo and also reduce transmission of
streptococci to susceptible individuals (see Box 48-2 ). None of
these treatments, including penicillin, prevents poststreptococcal
glomerulonephritis.
ERYSIPELAS
Erysipelas is caused exclusively by S pyogenes and is
characterized by an abrupt onset of fiery red swelling of the
face or extremities. Distinctive features are well-defined
margins, particularly along the nasolabial fold, scarlet or salmon
red rash, rapid progression, and intense pain. Flaccid bullae
Findings
Red rash
Pharyngitis
Red rash
Pharyngitis
Local invasion of vital structures of the neck
Red rash
Pharyngitis
Profound fever
(>108F)
Dehydration
Convulsions
Outcome
Slow, lingering death due to bleeding, suffocation
High mortality rate; rapid death due to status epilepticus,
dehydration, etc.
Benign
Table
Septic
Toxic
CELLULITIS
Group A streptococci are the most common cause of cellulitis;
however, alternative diagnoses may be obvious when associated
with a primary focus, such as an abscess or boil
(Staphylococcus
aureus ), dog bite (Capnocytophagia ), cat bite
(Pasteurella
multocida ), freshwater injury (Aeromonas
hydrophila ), seawater injury (Vibrio vulnifica ), animal
carcasses, Erysipelothrix
rhusiopathia , and so on. Clinical clues
to the etiologic diagnosis are important because aspiration of
the leading edge and punch biopsy yield a causative organism in
only 15% and 40% of cases, respectively. Patients with
lymphedema of any cause, such as lymphoma, filariasis, or
postsurgical regional lymph node dissection (eg, mastectomy,
carcinoma of the prostate), are predisposed to developing
streptococcal cellulitis, as are patients with chronic venous
stasis. Recently, recurrent saphenous vein donor site cellulitis
has been attributed to Group A, C, or G streptococci.
Group A streptococci may invade the epidermis and
subcutaneous tissues, resulting in local swelling, erythema, and
pain. The skin becomes indurated and, unlike the brilliant
redness of erysipelas, is a pinkish color. If fever, pain, or
swelling increase, if bluish or violet bullae or discoloration
appear, or if signs of systemic toxicity develop, a deeper
infection, such as necrotizing fasciitis or myositis, should be
considered (see below). An elevated serum creatinine
phosphokinase suggests deeper infection, and prompt surgical
inspection and dbridement should be performed (see Box 484 ).
First Choice
<60 lbs:
Penicillin G or V, 200,000 U (125 mg) QID 10 days
>60 lbs:
Penicillin G or V, 400,000 U (250 mg) QID 10 days
Second Choice
<60 lbs:
Dicloxacillin, 125 mg QID 10 days
>60 lbs:
Dicloxacillin, 250500 mg QID 10 days
Options for Penicillin-Allergic Patients
Erythromycin ethylsuccinate, 4050 mg/kg QID 10 days
P O1
Erythromycin ethylsuccinate, 4050 mg/kg QID 10 days
P O1
1
Adults
LYMPHANGITIS
Cutaneous infection with bright red streaks ascending
proximally is invariably caused by Group A streptococcus.
Prompt parenteral antibiotic treatment is mandatory since
bacteremia and systemic toxicity develop rapidly once
streptococci reach the bloodstream via the thoracic duct.
NECROTIZING
FASCIITIS
MYOSITIS
Historically, streptococcal myositis has been an extremely
uncommon infection, only 21 cases being documented from
1900 to 1985. Recently, the prevalence of streptococcal
myositis has increased in the United States, Norway, and
Sweden. Translocation of streptococci from the pharynx to the
deep site of trauma (muscle) likely occurs hematogenously.
Symptomatic pharyngitis or penetrating trauma is uncommon.
Severe pain may be the only presenting symptom; swelling and
erythema may be the only signs of infection. In most cases, a
single muscle group is involved; however, because patients are
frequently bacteremic, multiple sites of myositis or abscess can
occur.
Distinguishing streptococcal myositis from spontaneous gas
gangrene caused by C perfringens or C septicum may be
difficult, although the presence of crepitus or gas in the tissue
would favor clostridial infection. Myositis is easily distinguished
from necrotizing fasciitis anatomically by surgical exploration
P.507
or incisional biopsy, although clinical features of both conditions
overlap and both necrotizing fasciitis and myonecrosis may
occur together.
First
Choice
Adults
PNEUMONIA
Pneumonia caused by Group A streptococcus is most common in
women in the second and third decades of life and causes large
pleural effusions and empyema. Several liters of pleural fluid
may accumulate within hours. Chest tube drainage is
mandatory, although management is complicated by multiple
loculations and fibrinous effusions, resulting in restrictive lung
disease.
STREPTOCOCCAL
SYNDROME
TOXIC
SHOCK
Clinical
Findings
shown in
aggressive
mechanical
fasciotomy,
Nonsuppurative
The
nonsuppurative
Complications
complications
failure.
First Choice
<60 lbs:
Benzathine penicillin, 600,000 units IM, once per month
>60 lbs:
Benzathine penicillin, 1.2 million units IM, once per month
Second Choice
Phenoxomethyl penicillin, 250 mg q day, PO
Phenoxomethyl penicillin, 250 mg q day, PO
Options for Penicillin-Allergic Patients
Erythromycin 250 mg/day, PO1 O R <60 lbs: sulfadizine orally,
0.5 gm/day
Erythromycin 250 mg/day QID 10 days PO1 O R >60 lbs:
sulfadizine, 1 gm/day
1 Oral cephalosporins, such as cefalexin, cephradine, cefadroxil,
cefaclor, cefixime, cefuroxime, cefpodoxime, and cefdinir, given
orally for 10 days, are good alternatives to erythromycin in
penicillin-allergic
patients.
Children
Adults
Treatment
of
Group
Infections
During epidemics, particularly when rheumatic fever or a poststreptococcal glomerulonephritis are prevalent, treatment of
asymptomatic carriers may be necessary. Studies by the U.S.
military have shown that monthly injections of benzathine
penicillin greatly reduce the incidence of streptococcal
pharyngitis and rheumatic fever in young soldiers living in
crowded
conditions.
Erythromycin resistance of S pyogenes is currently 4% in
Western countries; however, in Japan in 1974, the rate reached
72%. Sulfonamide resistance currently is reported in <1% of
GAS isolates.
Resistance to penicillin has not been described, yet in some
settings there is a lack of in vivo efficacy despite in vitro
susceptibility to penicillin. Three mechanisms may explain this
lack of efficacy.
Penicillin failure in pharyngitis, tonsillitis, or mixed infections
may be caused by inactivation of penicillin in situ by beta
lactamases produced by cocolonizing organisms such as
Bacteroides fragilis, Haemophilus influenzae , or S aureus. For
example, the failure rate of penicillin treatment of GAS
pharyngitis may approach 25%, and, if such patients are treated
with a second course of penicillin, the failure rate may approach
80%, perhaps owing to selection of beta-lactamaseproducing
bacteria. In contrast, cures of 90% have been achieved when
REFERENCES
Bisno AL: Group A streptococcal infections and acute
rheumatic fever. N Engl J Med 1991;325:783. (An excellent
review article about Group A streptococcus. The emphasis of
this chapter is on rheumatic fever but there are excellent
sections on virulence factors, epidemiology, and
streptococcal infections in general.)
Cone LA, Woodard DR, Schlievert PM, et al: Clinical and
bacteriologic observations of a toxic-shock like syndrome
due to Streptococcus pyogenes. N Engl J Med 1987;317:146.
(Case report of an early case of streptococcal toxic shock
syndrome.)
Martin PR, Hoiby EA: Streptococcal serogroup A epidemic in
Norway 19871988. Scand J Infect Dis 1990;22:421. (An
excellent population-based study demonstrating a
remarkable recent increase in Group A streptococcal
bacteremia in age groups from 18 to 50 years of age.)
Schwartz B, Facklam RR, Breiman RF: Changing
epidemiology of Group A streptococcal infection in the USA.
Lancet 1990;336:1167. (A survey of Group A streptococcal
isolates sent to the CDC over the last decade. A clear
indication that invasive infections are currently associated
with M types 1 and 3.)
2001
McGraw-Hill
49
Enterococci
Robin Patel MD
Essentials
of
Diagnosis
General
Considerations
nosocomial
enterococcal
infection.
CLINICAL
URINARY
Urinary tract
pyelonephritis,
most common
(Box 49-1 ).
SYNDROMES
TRACT
INFECTION
BACTEREMIA
Nosocomial
&
enterococcal
ENDOCARDITIS
bacteremias
are
commonly
of the mitral than the aortic valve. The typical clinical course of
enterococcal endocarditis is that of subacute bacterial
endocarditis. There is a suggestion that the relapse rate is
higher in patients who have had symptoms of endocarditis for
3 months before treatment, which has implications for
length of therapy (see below).
More
Common
Urinary tract
Bacteremia
infection
Endocarditis
Wound and soft tissue infection
Intra-abdominal and pelvic infection
Less
Common
Meningitis
Neonatal
BOX
49-1
sepsis
Enterococcal
Infections
INTRA-ABDOMINAL
INFECTION
&
PELVIC
MENINGITIS
Enterococci rarely cause meningitis. Most cases occur in
patients who have anatomic defects of the central nervous
system or who have had previous neurosurgery or head trauma.
Rarely, however, meningitis may be a complication of highgrade bacteremia such as that seen in patients with
enterococcal endocarditis. Meningitis may also be seen in
association with enterococcal bacteremia in patients with human
immunodeficiency virus infection and acute leukemia and in
neonates
and
transplant
NEONATAL
recipients.
SEPSIS
Diagnosis
The diagnosis of enterococcal infection is made by isolating
enterococci from typically sterile sites (eg, urine, blood, intra-
Treatment
Penicillin or ampicillin remains the antibiotic of choice for
treating enterococcal infections such as urinary tract infections,
peritonitis, and wound infections (ie, infections that do not
require bactericidal treatment) (Box 49-2 ). Vancomycin is the
alternative agent for patients allergic to penicillin or for
organisms with high-level penicillin resistance that are lactamase negative and vancomycin susceptible.
Combination therapy with a cell wall-active agent such as
penicillin, ampicillin, or vancomycin, along with an
aminoglycoside, is essential for the treatment of enterococcal
endocarditis and probably for enterococcal meningitis as well.
The situation is not as clear-cut for enterococcal bacteremia
alone; there is no consensus as to whether combination therapy
is required in this setting.
Prevention
Prophylaxis
for
&
Control
Infective
Endocarditis.
Antimicrobial
prophylaxis
in Chapter 11 .
Choice
Second
Choice
Considerations
Penicillin
Resistance,
OR
Levofloxacin, 250 mg orally every d
OR
Norfloxacin, 400 mg orally every 12 h
OR
Enoxacin, 200400 mg orally every 12 h
OR
Gatifloxacin, 200400 mg orally every d
Vancomycin, 30 mg/kg/24 h IV in 2 doses, not to exceed 2
g/24 h unless serum levels are monitored with or without
gentamicin2 (1 mg/kg IV/IM every 8 h)
Vancomycin
and
Penicillin
Resistance
Uncomplicated
Urinary Tract
Infection
Bacteremia, Intraabdominal or
Pelvic Infection, Wound or Soft
Tissue Infection, and Neonatal
Sepsis
Discouraged
a wound
leaving the
hands should
antiseptic
agent.
Dedicated noncritical items such as stethoscopes,
sphygmomanometers, and rectal thermometers should be
assigned to a single patient or cohort of patients infected or
colonized with VRE.
If such devices are to be used on other patients, they
should be adequately cleaned and disinfected first.
BOX 49-3 Prevention of VRE Transmission
In addition, education programs concerning the epidemiology of
VRE and the potential impact of this pathogen on the cost and
outcome of patient care were recommended for hospital staff
including attending and consulting physicians; medical residents
and students; pharmacy, nursing, and laboratory personnel; and
other direct patient care providers. Specific recommendations
were also issued for the microbiology laboratory regarding the
detection, reporting, and control of VRE. In addition,
recommendations were given regarding how to proceed when
VRE are isolated from a clinical specimen, how to screen for
detection of VRE, and how to prevent transmission of VRE once
identified (Box 49-3 ). Recommendations for screening for
roommates found to be infected or colonized with VRE were also
issued.
REFERENCES
Centers for Disease Control and Infection: Nosocomial
enterococci resistant to vancomycinUnited States,
19891993. Morbid Mortal Weekly Rep 1993; 42:
59799.
Hospital Infection Control Practices Committee. 1995
Recommendations for preventing the spread of vancomycin
resistance. J Infect Control Hosp Epidemiol 1995;6:
10513.
2001
McGraw-Hill
Gram-Positive
Cocci
50
Other
Gram-Positive
Cocci
Robin Patel MD
VIRIDANS
GROUP
STREPTOCOCCI,
INCLUDING ABIOTROPHIA
DEFECTIVA
& ABIOTROPHIA
ADJACENS
Essentials
of
Diagnosis
cocci,
catalase
General
Considerations
significantly,
are
group of
constellatus,
CLINICAL
1.
SYNDROMES
ENDOCARDITIS
2.
BACTEREMIA
Organisms
Viridans
group
Syndromes
Endocarditis
streptococci
(including
Abiotropha spp.)
Bacteremia, especially in
febrile neutropenic patients
Meningitis
Other infections
Group B
Streptococcus
(Streptococcus
agalactiae)
Neonatal infection:
bacteremia,
pneumonia,
meningitis, bone and joint
infection
Postpartum
infection:
bacteremia,
endometritis,
endoperimetritis
Group B streptococcal infection
in adults: pneumonia,
endocarditis,
arthritis,
osteomyelitis, skin and soft
tissue infections
S dysqalactiae
subspp.
equisimilis and
S zooepidemicus
Pharyngitis
Post-streptococcal
glomerulonephritis
Cutaneous and subcutaneous
infections
Arthritis/osteomyelitis
Endocarditis
S bovis
Bacteremia
Endocarditis
Urinary tract infection
Meningitis
Neonatal sepsis
bacteremia.
3.
MENINGITIS
4. OTHER VIRIDANS
INFECTIONS
STREPTOCOCCI
mediastinitis,
cellulitis.
brain
abscesses,
Diagnosis
The diagnosis of viridans streptococcal infection is made by
isolating viridans streptococci from typically sterile sites. As
mentioned above, communityacquired viridans streptococcal
bacteremias are strongly associated with bacterial endocarditis.
This diagnosis may be further confirmed by the presence of
clinical findings consistent with endocarditis as well as by the
use of echocardiography. A defectiva and A adjacens require
pyridoxal or thiol group supplementation for growth. There is
sufficient pyridoxal in human blood to support the growth of A
defectiva and A adjacens in most blood culture media (with the
notable exception of unsupplemented tryptic soy broth). For
subculture, however, solid media must be supplemented with
0.001% pyridoxal or 0.01% L-cysteine to sustain growth. As an
alternative, the culture plate may be cross-streaked with
Staphylococcus
aureus to provide these factors and permit the
growth of the streptococci as satellite colonies. In addition, as
noted above, members of the S milleri group are associated
with deep-seated abscesses in visceral organs. Therefore
infections caused by these organisms should alert the clinician
to initiate an appropriate investigation for the detection of a
possible subclinical focus of infection.
Treatment
Viridans streptococci with a minimum inhibitory concentration
(MIC) of 0.12 g/mL to penicillin are defined as penicillin
susceptible. Those with a penicillin MIC of 0.25 to 2.0 g/mL
are intermediately susceptible to penicillin. Those with a
penicillin MIC of > 2 g/mL are resistant to penicillin. A high
frequency of penicillin-resistant viridans streptococcal infections
Prevention
&
Control
GROUP B STREPTOCOCCUS (S
AGALACTIAE)
Essentials
of
Diagnosis
Group B streptococcus (S
agalactiae) .
Facultative
diplococci.
gram-positive
General
to
bacitracin
sodium
and
trimethoprim-sulfamethoxazole.
hippurate.
Considerations
delivery.
B streptococci are resistant to bacitracin and trimethoprimsulfamethoxazole, hydrolyze sodium hippurate, and produce
an orange pigment during anaerobic growth on certain
media. Group B streptococci produce CAMP (named for
Christie, Atkins, and Munch-Petersen) factor, which is a
thermostable extracellular protein that results in synergistic
hemolysis on sheep blood agar in conjunction with the
hemolysin
of S aureus.
CLINICAL
SYNDROMES
1. EARLY-ONSET
STREPTOCOCCAL
GROUP B
NEONATAL
INFECTION
grunting
respirations,
pallor,
and
hypotension.
follow.
2. LATE-ONSET GROUP B
STREPTOCOCCAL
NEONATAL
INFECTION
3.
PERIPARTUM
INFECTIONS
4. GROUP B
PNEUMONIA
STREPTOCOCCAL
5. ENDOCARDITIS
ONSET)
(ACUTE
OR
SUBACUTE
6.
ARTHRITIS
8. OTHER GROUP
INFECTIONS
STREPTOCOCCAL
Diagnosis
The diagnosis of group B streptococcal infection is made by the
isolation of the organism from typically sterile sites (eg, blood,
cerebrospinal fluid, abscess material). Antigen detection
methods may be used to permit a presumptive diagnosis,
especially in neonates. Countercurrent immunoelectrophoresis,
latex agglutination, staphylococcal coagglutination, and enzyme
immunoassays may be used to detect group B streptococcal
antigen in various body fluids. A number of selective media
enhance the accurate detection by culture of low numbers of
group B streptococci from sites such as the genital or
gastrointestinal tract of pregnant women. These media usually
contain Todd-Hewitt broth with or without sheep red blood cells
and antimicrobial agents such as nalidixic acid and gentamicin
or colistin. Molecular and antigen detection methods can also be
used to detect group B streptococcal genital or gastrointestinal
tract colonization in pregnant women.
Treatment
Group B streptococci are uniformly susceptible to penicillin,
although less so than S pyogenes. Penicillin G is therefore the
drug of choice; however, because of the increased penicillin MIC
(as compared with S pyogenes), the combination of penicillin
gentamicin.
Prevention
&
Control
STREPTOCOCCUS
DYSGALACTIAE
SUBSPP. EQUISILIMIS &
STREPTOCOCCUS
ZOOEPIDEMICUS
Essentials
Associated
of
with
Diagnosis
domestic
animals.
General
Considerations
Epidemiology. S
bypass
surgery.
Microbiology. S
and S
First
Choice
Second
Choice
monitored
Penicillin
Allergic
Vancomycin 30 mg/kg 24 h IV in 2
divided doses not to exceed 2 g/24
h unless serum levels are
monitored
Pediatric
Considerations
Penicillin G IV/IM,
100,000250,000 U/kg/24 h in
divided doses every 4 h PLUS
gentamicin 1 mg/kg IV/IM every 6
h
Ampicillin 100200 mg/kg/24 h
IV/IM in 46 divided doses
Vancomycin 10 mg/kg 6 h IV not to
exceed 2 g/24 h unless serum
levels are monitored
Ceftriaxone 50100 mg/kg 24 h
IV/IM not to exceed 4 g/24 h
Imipenem 12.5 mg/kg every 6 h
IV/IMnot to exceed 4 g/24 h
Cefazolin 25100 mg/kg 24 h
IV/IM in 34 divided doses
Cefotaxime 50180 mg/kg 24 h
IV/IMin 46 divided doses
1 Doses
2 Oral
CLINICAL
1.
SYNDROMES
PHARYNGITIS
Notably, however, no
response will be detected as these
streptolysin O. S dysgalactiae subspp.
been associated with sterile reactive
wound
infections,
pyoderma,
erysipelas,
impetigo,
and
(see
a portal of
equisimilis
with
3.
infections.
ARTHRITIS
Screening
Approach
Nonscreening
Intrapartum
antimicrobial
agents
Approach
P.525
4.
OTHER
INFECTIONS
Diagnosis
The diagnosis of S dysgalactiae subspp. equisimilis and S
zooepidemicus infection is made by isolating these organisms
from typically sterile sites.
Treatment
The antimicrobial agent of choice for S dysgalactiae subspp.
equisimilis and S zooepidemicus is penicillin G. Other agents
with good in vitro activity include cefazolin, vancomycin, the
semisynthetic penicillins, and cefotaxime (Box 50-2). The
addition of gentamicin to penicillin, cefotaxime, or vancomycin
may result in a better outcome in cases of serious infection such
as bacterial endocarditis caused by S dysgalactiae subspp.
equisimilis and S zooepidemicus.
STREPTOCOCCUS
BOVIS
Essentials
of
Diagnosis
General
arylamidase
reactivity
negative.
Considerations
CLINICAL
SYNDROMES
Diagnosis
Treatment
S bovis is very susceptible to penicillin (MICs range from 0.01
to 0.12 g/mL) (Box 50-2). Other effective agents include
ampicillin, the antipseudomonal penicillins, ceftriaxone,
erythromycin, clindamycin, and vancomycin. Penicillin alone
given for 4 weeks is adequate to treat patients with S bovis
endocarditis. Vancomycin is a reasonable alternative in
penicillin-allergic patients. Bacterial endocarditis prophylaxis
regimens are given in Chapter 11 and are relevant to S bovis
endocarditis.
OTHER
GRAM-POSITIVE
COCCI
STREPTOCOCCUS
INIAE
LEUCONOSTOC
SPECIES
Organisms
Streptococcus
iniae
Syndromes
Cellulitis
Bactermeia
Endocarditis
Meningitis
Septic arthritis
Leuconostoc spp.
Bacteremia
Line sepsis
Meningitis
Dental abscess
Pediococcus spp.
Bacteremia
Stomatococcus
mucilaginosus
Endocarditis
Bacteremia in febrile
neutropenic
patients
Line sepsis
Meningitis
Peritonitis
Aerococcus spp.
Endocarditis
Bacteremia
Urinary tract
Gemella spp.
Endocarditis
Meningitis
Arthritis
Bacteremia
infection
Urinary
Wound
Alloiococcus
otitis
Otitis
tract infection
infection
media
(possible
association)
Micrococcus spp.
Endocarditis
Lactococcus spp.
Endocarditis
Globicatella spp.
Bacteremia
Urinary tract
infection
Meningitis
Helcococcus
kunzii
Wound infection
association)
(possible
PEDIOCOCCUS SPECIES
Pediococcus spp. are also vancomycin-resistant gram-positive
cocci. They may be isolated from blood cultures, typically in
immunocompromised
patients.
STOMATOCOCCUS
MUCILAGINOSUS
Stomatococcus
mucilaginosus is a gram-positive coccus that
may cause endocarditis, bacteremia, intravascular catheter
AEROCOCCUS SPECIES
Although aerococci may appear as contaminants in clinical
cultures, occasional reports of a clinically significant role of
these organisms in cases of endocarditis, bacteremia, and
urinary tract infection have been noted. Aerococci are
susceptible to penicillin and vancomycin.
GEMELLA
SPECIES
Gemella
haemolysans has been isolated (as a pathogen) in
cases of endocarditis, meningitis, and prosthetic joint infections.
G morbillorum has been isolated from blood, respiratory,
genitourinary, wound, and abscess cultures and from an
infection of an arterial-venous shunt. Gemella spp. appear to be
susceptible to penicillin and vancomycin.
ALLOIOCOCCUS
OTITIS
MICROCOCCUS SPECIES
LACTOCOCCUS
SPECIES
GLOBICATELLA
SPECIES
Globicatella
sanguis, the sole species in this genus, has been
isolated from patients with bacteremia, urinary tract infection,
and meningitis.
HELCOCOCCUS
KUNZII
REFERENCES
Centers for Disease Control: Decreasing incidence of
perinatal group B streptococcal diseaseUnited States,
19931995.
1997;
46(21):473477.
Centers for Disease Control: Prevention of perinatal group B
streptococcal disease: a public health perspective. Morbid
Mortal Wkly Rep 1996;45(RR-7):124.
2001
McGraw-Hill
Aerobic
Bacilli
51
Gram-Positive
Aerobic
Bacilli
LISTERIA
Essentials
MONOCYTOGENES
of
Diagnosis
General
Considerations
Clinical
Findings (Box
51-1)
More
Common
Common
Granulomatosis
infantisepticam
Amnionitis
Bacteremia and/ or meningitis in patients with decreased
cell-mediated
immunity
Children
Adults
Diagnosis
L monocytogenes can be easily cultivated in the microbiology
laboratory from blood, CSF, meconium, gastric washings,
placenta, amniotic fluid, and other specimens. A CSF Gram stain
with gram-positive or-variable rods should suggest Listeria
infection, but this organism may be mistaken as a diphtheroid.
Treatment
There are no clinical trials comparing different antibiotic
regimens for the treatment of listeriosis. Ampicillin or penicillin
is generally recommended as the treatment of choice (Box 51-2
for
agent is
intracellular
species.
levels
Choice
Choice
sulfamethoxazole,
as
per
100
children
Allergic
sulfamethoxazole,
as
per
100
children
Adults
Prognosis
Listeria infection of the CNS is associated with a high mortality
outcome.
Prevention
Patients at risk for listeriosis should be advised on how to
minimize their exposure to this organism (Box 51-3 ). This
advice should include cooking well all food from animal sources,
washing raw vegetables thoroughly, and keeping uncooked meat
separated from vegetables and cooked foods. Patients should
also avoid consumption of unpasteurized milk, soft cheeses, or
foods made with raw milk, and they should wash hands, knives,
and cutting boards after handling uncooked food. An additional
recommendation for high-risk persons is to heat all leftovers or
ready-to-eat foods until these foods are steaming hot.
Prophylactic
Measures
Precautions
ANTHRAX
Essentials
of
Diagnosis
exposure.
General
Considerations
Clinical
Findings
More
Common
Common
Spectrum of disease
and meningeal
includes
inhalational,
gastrointestinal,
Diagnosis
An appropriate epidemiologic history involving animal exposure
is the cornerstone of the diagnosis of cutaneous anthrax. Other
diagnostic features include edema out of proportion to the size
of the skin lesion, the lack of pain during the initial phases of
the infection, and the rarity of polymorphonuclear leukocytes on
Gram stain. The organism can be readily cultivated and forms
nonhemolytic gray-white colonies. A critical diagnostic feature
of inhalational anthrax is a widened mediastinum on chest
radiography. Patients with this disease usually die before
organism growth in blood cultures is detected; however,
organisms can sometimes be detected in blood with the Gram
stain, owing to the high burden of bacteria in the endovascular
compartment.
Treatment (Box
51-5)
Choice
Choice
Considerations
disease
is
life-threatening
Allergic
Adults
Prevention
Doxycycline or ciprofloxacin (Box 51-6 ) may prevent
development of inhalational disease if given to exposed
OTHER B A C I L L U S SPECIES
General
Considerations
Clinical
Findings
Measures
Precautions
Standard
precautions
Contaminated dressings or bedclothes should be burned or
Treatment
B cereus is resistant to penicillin and other beta-lactam drugs,
including cephalosporins. Active antimicrobial agents include
vancomycin, clindamycin, aminoglycosides, carbapenems, and
ciprofloxacin.
Non-B cereus spp. are susceptible to penicillin and
cephalosporins. Appropriate empiric therapy for suspected
Bacillus spp. infections (other than anthrax) is vancomycin or
clindamycin, with or without an aminoglycoside. Intraocular
infections require aggressive therapy with systemic antibiotics
plus intravitreous clindamycin or an aminoglycoside.
Intravitreous dexamethasone and early vitrectomy are also
recommended for sight-threatening B cereus ocular infection.
DIPHTHERIA
Essentials
of
Diagnosis
and
paralysis.
stridor.
General
Considerations
Clinical
Findings (Box
51-7)
Respiratory
Diphtheria. The incubation period for
respiratory diphtheria is generally 24 days, but it can
last < 7 days. Initial symptoms include a low-grade fever.
Sore throat and malaise are the most common
manifestations of pharyngeal diphtheria. Unvaccinated
patients tend to have more severe disease. The
development of cell necrosis, secondary to the exotoxin, is
commensurate with the presence of the characteristic
membrane (Figure 51-2A ). Initially the membrane is white
and smooth, but later it becomes gray with patches of green
and black necrosis. As the membrane spreads, it can
interfere with airflow. Involvement of the posterior pharynx
is often accompanied by cervical adenopathy and swelling,
giving rise to a bull neck appearance (Figure 51-2B
). With extensive disease there is increased release of
exotoxin, resulting in myocardial and neurologic
complications, thereby increasing the mortality associated
with this disease.
Cutaneous
Diphtheria. Cutaneous diphtheria usually
begins with pustules that progress to ulcer formation with a
gray-brown membrane at the base. Commonly, C
diphtheriae will superinfect existing skin lesions such as
insect bites, ecthyma, and impetigo. Cutaneous infections
induce high levels of antitoxin antibody that prevent
progression to systemic disease; therefore, the infections
tend to be indolent and are not usually associated with signs
of intoxication. Cutaneous infection poses a greater risk of
environmental contamination and transmission to others
than does pharyngeal infection.
Cardiac Disease. Myocarditis with clinically-significant
cardiac dysfunction is observed in 1020% of patients
with pharyngeal disease. The likelihood and severity of
myocarditis are correlated with the extent and severity of
respiratory tract compromise. ST segment and T-wave
changes and first-degree block are found by
electrocardiography in less severe disease, whereas left
bundle branch block and atrioventricular block are
associated with high mortality. In severe cases, patients
usually sustain permanent injury to the myocardium.
Neurologic
Disease. Neurologic complications occur in ~
10% of respiratory cases and are predicted by the severity
of respiratory tract involvement. Symptoms and signs
develop 1028 days after the respiratory complaints and
reflect both cranial nerve involvement and a peripheral
neuropathy that can lead to complete paralysis. These
complications are usually reversible.
More
Common
Membranous
nasopharyngitis
Obstructive
laryngotracheitis
Abrupt onset low-grade fever, malaise
Less
Common
Cutanous
Vaginal
Conjunctival
Otic
Complications
including
cardiac
and
neurologic
toxicity
Diagnosis
Prompt recognition and treatment of respiratory diphtheria are
critical for preventing complications and mortality. A dark
pharyngeal membrane that cannot be removed without bleeding,
systemic toxicity, neurologic abnormalities such as 9th and 10th
cranial nerve deficits, and/or electrocardiograph changes should
alert the clinician to the possibility of diphtheria. The
microbiology laboratory should be notified about the possibility
of diphtheria, because special media, such as Loeffler's or
tellurite selective media, must be used to prevent overgrowth of
normal flora.
Treatment
All patients should be hospitalized and isolated. Rapid institution
of antitoxin is critical because it is most effective if given within
4 days of the onset of illness (Box 51-8 ). Hyperimmune
antiserum produced
P.535
in horses has been used for > 100 years. The dose of antitoxin
is adjusted to the severity of disease. Sensitivity of the patient
to horse protein must be assessed (see recommendations in Box
51-8 ). An initial scratch test may be performed on the volar
forearm with a 1:100 dilution. If negative, this should be
followed by an intracutaneous injection of 0.02 mL of a 1:1000
dilution of antitoxin in saline. No additional benefit is provided
by repeated doses. Antibiotics should be initiated as soon as
possible to kill organisms, stop toxin production, and eliminate
First
Choice
Choice
U/kg/d
Allergic
Erythromycin
Erythromycin
Children
Adults
Prophylactic
Measures
2 g/d
U for
4- to 83rd dose)
Children >7 y and adults, dT (2 IM injections at 4- to 8wk intervals, then a 3rd IM dose 612 mo after 2nd dose)
Booster
Children receiving primary series <4 wk, DTaP at school
entry, then every 10 y
Children/adults, dT every 10 y
Isolation
Precautions
Prevention
Children 6 weeks to 7 years of age should be immunized with
three injections of vaccine containing formalin-inactivated
diphtheria toxin (Box 51-9 ). Susceptibility to diphtheria
correlates inversely with serum levels of anti-toxin antibody.
Because these levels wane, adults should receive booster
vaccinations every 10 years.
CORYNEBACTERIUM
JEIKEIUM
OTHER CORYNEBACTERIUM
SPECIES
ERYSIPELOTHRIX
General
RHUSIOPATHIAE
Considerations
Erysipelothrix
rhusiopathiae is a gram-positive bacillus that
causes occupationally related skin infections and, rarely,
septicemia in humans.
P.537
Epidemiology. E rhusiopathiae is ubiquitous in nature and
is an uncommon cause of human disease. It can infect
mammals, birds, fish, shellfish, and insects, and it may
reside in swine, which serve as a reservoir. Disease in
humans is most commonly seen in persons with an
appropriate exposure, usually including butchers,
slaughterhouse workers, and especially fish handlers. Most
cases of skin infection (erysipeloid) occur in the
Clinical
Findings
Diagnosis
The diagnosis requires an appropriate epidemiologic history. The
skin lesion may resemble erysipelas caused by Streptococcus
pyogenes , but the rate of progression is slower, and there is a
lack of lymphangitis, lymphadenopathy, and systemic
symptoms. Full-thickness skin biopsy with appropriate culture
will yield the organism in the majority of cases. Blood cultures
should also be obtained.
Treatment
Treatment of choice for E
REFERENCES
Bisgard KM, et al: Respiratory diphtheria in the United
States, 1980 through 1995. Am J Publ Health 1998;88: 787.
Cossart P, Lecuit M: Interactions of Listeria
monocytogenes
2001
McGraw-Hill
Gonorrhoeae
&
Neisseria
Meningitidis
52
Neisseria
Neisseria
Gonorrhoeae &
Meningitidis
D. Scott Smith MD
David A. Relman MD
Neisseria
gonorrhoeae was first described by Albert Neisser in
1879, in the ocular discharge and exudate from newborn infants
with conjunctivitis. Descriptions of a condition resembling the
disease gonorrhea can be found in the written record as early as
130 AD, when Galen created a descriptor for the malady by
using the Greek words gonos (seed) and rhoea (flow) to
characterize what was believed to be the morbid loss of semen.
Neisseria
meningitidis is thought to be responsible for epidemics
in the Napoleonic and Persian armies in the early 1800s. The
pathogen was first described in 1886 by Weichselbaum, who
observed gram-negative diplococci in the cerebrospinal fluid
(CSF) of a young patient who died with purulent meningitis.
Within the family Neisseriaceae , there are five
generaNeisseria, Branhamella, Moraxella, Kingella , and
Acinetobacter. N meningitidis and N gonorrhoeae are the
organisms that are pathogenic for humans in the Neisseria
genus (Table 52-1 ). Approximately 10 other Neisseria species
have been isolated from humans, but these usually establish a
NEISSERIA
GONORRHOEAE
Essentials
Transmission
of
Diagnosis
associated
with
unprotected
sex.
dysuria,
Dermatitis-arthritis
syndrome
intermenstrual
with
bleeding
disseminated
in
infection.
General
and
specificity.
Considerations
Gram-stain of cervical or urethral swab shows gramnegative diplococci in association with PMNs.
Culture of the affected site demonstrates the organism.
Gram stain: gram-negative intracellular diplococci.
CSF: cloudy, purulent, high levkocyte count with PMN
predominance, increased protein, decreased glucose.
Culture of CSF, blood, or aspirated petecchial lesion
demonstrates
organism.
Latex agglutination of CSF or urine may be indicated in
treated patients but is similar to Gram stain of CSF for
sensitivity.
Epidemiology
Sexual
transmission.
Crowded or closed population settings (eg, boarding schools
and military camps).
Most cases in children and young adults.
Neisseria
Table
gonorrhoeae
Neisseria
meningitidis
Clinical
Genital
Findings
infection
with N
adhesions
between
Diagnosis
The cornerstone of diagnosis is the Gram stain or culture. One
is looking for gram-negative diplococci associated with
neutrophils. Gram stain of urethral exudate from men has a
sensitivity of 90% and specificity of 98% when compared with
culture. Staining of endocervical exudates is 50% sensitive and
95% specific in the hands of an experienced microscopist.
Treatment
Many antibiotics are safe and
gonorrhoeae (Box 52-1 ). In
must be given to the site of
infections, and the possibility
pallidum. .
Prevention
&
Control
NEISSERIA
Essentials
MENINGITIDIS
of
Diagnosis
on
stained
widely
General
available.
Considerations
development.
gonorrhoeae section.
First
choice:
proctitis,
Uncomplicated
prostatitis,
urethritis,
ophthalmia
cervicitis,
neonatorum,
pharyngitis,
conjunctivitis1
infections:
(dermatitis-arthritis
Disseminated
syndrome),
gonococcal
infection
meningitis,4 endocarditis
Children
gonorrhoeae Infection
Prophylactic
measures
Avoid sexual exposure: abstinence, barrier methods (ie,
condoms).
Chemoprophylaxis (ie, post exposure for sexual assault1 )
Ceftriaxone, 125 mg IM single dose
PLUS
Metronidazole, 2 g orally in a single dose
PLUS
Azithromycin, 1 g orally in a single dose
OR
Doxycycline, 100 mg orally twice a day for 7 d
Postexposure hepatitis B vaccination (without HBIG)
Control
Case finding by active surveillance.
Treat contacts of known cases (epidemiologic
treatment) if the risk of unnecessary therapy is less than
the risk of developing complications of the infection or the
probability of transmission to other contacts
Isolation
Precautions
None
1
Clinical
N
Findings
in
some
developing
countries.
Diagnosis
The diagnosis of meningococcal infection is made by isolation of
the organism or detection of its antigen from blood or
cerebrospinal fluid (CSF). If possible, blood, CSF, throat swab,
and petecchial lesions should be cultured prior to antibiotic use.
Collection of these specimens, however, should never delay
treatment. Leukocytosis is often as high as 20,00030,000
cells/mm3 . Blood cultures are positive in 50% of cases of
meningitis before antibiotics
antibiotics are given. Gram
~ 70% of cases. This is a
antibiotics have been given
be obtained.
Differential
Diagnosis
Treatment
Treatment should be initiated as soon as the diagnosis is
considered (Box 52-3 ). Intravenous penicillin G or ceftriaxone
is the standard of therapy. The duration of therapy is dependent
on the clinical response, but 7 d is considered adequate for both
meningitis and chronic meningococcemia.
The clinical importance of isolates found to have altered
penicillin-binding proteins with intermediate resistance to
penicillin (MIC of 0.11.0 g/ml) is unclear, as patients with
these strains respond well to penicillin. For patients who do not
respond adequately to therapy, the bacterial isolate should be
tested for antibiotic resistance, and the therapy changed to
ceftriaxone or cefotaxime if the isolate is resistant to penicillin.
N
Choice
Children
meningitidis Infection
P.546
Prophylactic
Measures
Quadrivalent
vaccine1 (A, C, Y, W135) (Menomune) 0.5
ml SC 1 (may need to be repeated if <4 y old)
Control
with
chemoprophylaxis
Prevention
&
Control
REFERENCES
Neisseria
gonorrhoeae
Neisseria
gonorrhoeae.
meningitidis
Science
2000;287:1816.
2001
McGraw-Hill
> Table of Contents > Section V - Bacterial Infections > 53 Enteritis Caused by Escherichia coli & Shigella & Salmonella
Species
53
Enteritis Caused by Escherichia
coli & Shigella & Salmonella
Species
Gary W. Procop MD
Franklin Cockerill III MD
Essentials
of
Diagnosis
of
enteric
General
Considerations
by Y
ESCHERICHIA
COLI
Essentials
Diagnosis
of
EHEC).
E coli -induced enteritis is also indicated by microbiologic
isolation and identification of enteric pathogens or molecular
evidence of infection in the appropriate clinical setting.
More
Common
Enterocolitis
Enterocolitis
Less
Common
Adults
General
Considerations
identification,
of VT,
Like the
been
CLINICAL
SYNDROMES
1. ETEC
Clinical
Findings
2. EHEC
Clinical
Findings
3. EIEC
Clinical
Findings
4.
ENTEROADHERENT E COLI
Clinical
Findings
Differential
Diagnosis
Complications
All of the diarrheagenic E coli may produce dehydration and
electrolyte abnormalities. The EAggEC may cause chronic
disease and EIEC, like Shigella species, may cause a proteinlosing enteropathy if dysentery is produced. Disease secondary
to these agents is usually most pronounced in children, who
may become dehydrated rapidly.
The most severe complication of EHEC infection is the
development of HUS. This devastating disease most commonly
occurs in children and has a significant mortality rate
(3%10%). Patients develop microangiopathic hemolytic
anemia, thrombocytopenia, and renal failure. Patients that do
not succumb may suffer significant morbidity secondary to renal
and central nervous system dysfunction.
Diagnosis
Enteritis caused by the ETEC, EPEC, EIEC, DAEC, and EAggEC is
usually self-limited and may be associated with travel or a
particular outbreak. In most instances, the presence of one of
these organisms is assumed, and the diagnosis is based on
history, physical examination, and the exclusion of other enteric
pathogens. A definitive diagnosis cannot be made, unless
specific assays are performed. These confirmatory assays are
costly and usually clinically unnecessary. In outbreak situations,
however, complete microbiologic characterization of clinical
isolates, with strain analysis, may be warranted for public
health
purposes.
Treatment
Treatment of fluid and electrolyte loss is usually achieved
through oral rehydration. The use of the World Health
Organization Oral Rehydration Salts (ORS) solution is
recommended. Intravenous rehydration may be necessary for
infants, individuals with excessive vomiting, or those with
severe
dehydration.
Bismuth subsalicylate, 1 oz of liquid or two (262.5-mg) tablets
taken every 30 min for 4 h, may decrease the amount of
diarrhea and the duration of disease. Antimicrobial therapy is
generally not indicated, because of the self-limited nature of
most of these diseases. Some contend that empiric therapy may
decrease symptomatology and shorten the clinical course. It is a
concern, however, that the overuse of antimicrobial agents will
promote resistant strains. If chronic or persistent diarrhea
develops in patients infected by one of the enteroadherent E coli
strains, specific antimicrobial therapy should be used. If
available, the antimicrobial susceptibility profile should be used
to guide therapy. If unavailable, a trial of empiric therapy for E
coli is warranted (Box 53-2 ). Antimicrobial therapy has not
been shown to decrease the morbidity/mortality of patients with
HC/HUS. Antimicrobial therapy may worsen the clinical course,
possibly by decreasing competitive enteric flora. A synthetic
analog of G3b and diatomaceous earth, SYNSORB-Pk (Synsorb
Biotech, Inc.), holds promise as a treatment of HC/HUS. Taken
orally, this agent should absorb the VT and, it is hoped, prevent
HUS.
As previously noted, disease caused by the EIEC is very much
like shigellosis. It is unclear, however, if duration of disease and
shedding of viable organisms by patients infected with EIEC are
diminished by antimicrobial therapy, as occurs in patients with
shigellosis. The diagnosis of EIEC infection requires the isolation
of the organism; therefore, an antimicrobial susceptibility
profile should be available to guide therapy.
First
Choice
Adults
Prevention
&
Control
Measures
Precautions
S H I G E L L A SPECIES
Essentials
of
Diagnosis
flexneri ).
General
Considerations
(serogroup
either
diarrhea that
disease is largely
dysenteriae and S
Clinical
Findings
Diagnosis
Patients with acute diarrhea, which may be watery to
dysenteric; fever; abdominal pain; and systemic
symptomatology/toxemia may have shigellosis. A history of
exposure to individuals with shigellosis, travel to endemic areas,
and exposure to a high-risk population, such as persons in a
custodial-care facility, should raise the index of suspicion. The
presence of leukocytes in the stool, although supportive, is by
no means definitive for shigellosis. Fecal leukocytes may be
present in the stools of patients with other bacterial enteritides,
amoebic dysentery, pseudomembranous colitis, and
noninfectious disease, such as inflammatory-bowel disease. The
definitive diagnosis requires the microbiologic identification of a
Shigella species.
Shigellae are particularly susceptible to some environmental
changes, and they die rapidly in transport. Therefore, it is
imperative to rapidly transport the stool of patients suspected
of having shigellosis to the laboratory. This is especially
important for patients in the latter stages of disease, in whom
the number of shigellae in the stool are relatively few.
First Choice
Trimethoprim-sulfamethoxazole
(TMP/SMX)
Adults
Treatment
Fluid and electrolyte replacements are necessary for patients
with dehydration. In most instances, this is readily
accomplished by oral rehydration. Unlike in many other bacterial
enteritides, antibiotic therapy is important in the treatment of
shigellosis (Box 53-4 ). Antibiotic therapy limits the clinical
course of the disease, may decrease the likelihood of intestinal
complications, and decreases the fecal excretion of viable
pathogenic organisms, which in turn diminishes transmission.
Fluoroquinolones are the treatment of choice for adults.
TMP/SMX is the treatment of choice for children. Alternatives
are ampicillin, chloramphenicol, and nalidixic acid. In areas of
known resistance to TMP/SMX, such as parts of Southeast Asia,
Africa, and South America, quinolones should be used for
adults, and one of the above mentioned alternatives for children
with shigellosis. When available, the antimicrobial-susceptibility
profile should guide therapy.
Prognosis
The prognosis is generally good for patients with endemic or
sporadic shigellosis. Infants and the elderly, especially if
malnourished, suffer the highest mortality. Epidemic shigellosis
caused by S dysenteriae , however, is a severe and often lifethreatening disease with mortality rates from 5% to 20%. This
disease must be treated aggressively with antimicrobial and
rehydration
therapies.
Prevention
&
Control
SALMONELLA
SPECIES
Essentials
Diagnosis
I.
Enteric
of
fever
II. Salmonella
enteritis
General
Considerations
help
differentiate Salmonella species from some of the other
hydrogen sulfide producers and to detect Y enterocolitica.
Isolates with an appropriate biochemical profile in the threetube set are often serotyped and definitively identified by
traditional or automated biochemical testing.
For patients with enteric fever, the percent yield from blood
or bone marrow culture vs stool culture varies during the
course of disease (see Clinical Findings ). Clinicians must be
aware of which sites render the highest yield during each
phase of the disease and submit appropriate specimens for
culture.
Pathogenesis.
Enteric
symptoms,
recovery,
and
possible
carriage.
ENTERIC
Clinical
FEVER
Findings
Diagnosis
In the appropriate clinical setting, the definitive diagnosis of
enteric fever requires isolation and biochemical characterization
of the etiologic agent. Febrile patients who have visited endemic
areas may have enteric fever. Some patients with enteric fever
may have an insidious onset, but eventually become severely ill.
The Widal antigen/antibody agglutination is a presumptive test
that is still used for the diagnosis of typhoid fever. This test,
however, lacks both sensitivity and specificity. Blood and/or
bone marrow culture, followed by empiric therapy, is a more
reliable method of diagnosing enteric fever. Early in the course
of disease, blood and bone marrow cultures yield the highest
recovery of organisms, while later in the course of disease,
stool and sometimes urine cultures are more likely to become
positive. The submission of appropriate specimens for culture is
important, so that rapid isolation of the causative agent and
susceptibility testing can be performed. Antimicrobial
susceptibility testing is necessary to optimally direct therapy,
because of possible antimicrobial resistance.
Treatment
Chloramphenicol, TMP/SMX, ampicillin, third-generation
cephalosporins, and quinolones have been used successfully for
the treatment of enteric fever (Box 53-5 ). Unfortunately,
antimicrobial resistance has emerged to each of these agents.
Some Salmonella isolates are multidrug resistant. For this
reason, whenever possible, antimicrobial therapy should be
based on an individual isolate's susceptibility profile, obtained
by standard methods. Until such data are available, empiric
therapy should be used, based on known antimicrobialresistance
profiles.
Chloramphenicol was the first drug used for the treatment of
typhoid fever. However, increasing resistance, high relapse
rates, bone marrow toxicity, and the promotion of a chronic
cephalosporins.
SALMONELLA
Clinical
ENTERITIS
Findings
frequently
P.563
typhimurium , occurs between 12 and 48 h after the
consumption of contaminated food. Patients experience
fever, abdominal cramping, and diarrhea that may be
accompanied by nausea and vomiting. The diarrhea varies in
consistency from watery to dysenteric.
Laboratory
Findings. Microscopic examination of the stool
usually discloses nonspecific neutrophils.
Differential
Diagnosis. The differential diagnosis of
infectious diarrhea includes parasitic, viral, and bacterial
etiologies. Noninfectious causes of diarrhea, such as
inflammatory-bowel
disease,
lymphocytic/collagenous
colitis, neoplasia, and numerous other disorders, must be
considered. Patients with inflammatory-bowel disease may
also have fecal leukocytes, further limiting the usefulness of
this test. An accurate diagnosis can be achieved with a
thorough history and physical examination, excluding
enteric pathogens by appropriate microbiologic studies, and
obtaining and reviewing gastrointestinal biopsies by using
endoscopy and histopathologic studies.
Complications. In immunocompetent individuals, the
disease usually lasts < 1 week and resolves without specific
antimicrobial therapy. Neonates and young children, the
elderly, and pregnant women are at increased risk for
severe disease. In addition, immunocompromised individuals
and patients with sickle cell disease or other
hemoglobinopathies are at increased risk for bacteremia and
the establishment of metastatic foci of infection. The
complications of Salmonella infections may be separated
into four categories: (i) dehydration and electrolyte
abnormalities, (ii) local inflammatory response, (iii)
bacteremia with the spread of organisms to distant sites,
and (iv) postinfectious arthritis.
Extensive
diarrhea. Regardless of the cause, extensive
diarrhea may lead to fluid and electrolyte abnormalities.
lymphoid
hypertrophy.
Mesenteric
First Choice
Ceftriaxone:
>4 wk: 50100 mg/kg/d IV every 1224 h
14 wk: 5075 mg/kg d IV every 24 h
<1 wk: 50 mg/kg/d IV every 24 h
Ceftriaxone, 12 g IV every 12 h
Second Choice
Ampicillin:
>1 month: 25 mg/kg IV or orally every 6 h
Adults
Diagnosis
Patients with Salmonella enteritis have positive stool cultures
and occasionally positive blood cultures. Apart from the agents
of enteric fever, Salmonella
cholerasuis is more likely to result
in bacteremia than other Salmonella species. After isolation,
Salmonella species are rapidly grouped by using antisera and
are differentiated by various biochemical reactions.
Treatment
Uncomplicated enteritis caused by Salmonella species should
not be treated with antimicrobial agents. Antimicrobial agents
may prolong bacteria shedding and promote antimicrobial
resistance. Fluid and electrolyte replacement should be used to
treat dehydration. In most instances, oral rehydration is
sufficient, but, if severe electrolyte anomalies exist, intravenous
rehydration may be necessary. Antimotility agents should not be
used, because these agents inhibit the clearance of pathogenic
bacteria and their toxins. Patients at risk for or with systemic
disease/complications should be treated. A third-generation
cephalosporin, such as ceftriaxone, may be used for patients
with severe disease, until antimicrobial susceptibility data are
available (see Box 53-5 ). Prophylactic therapy is appropriate
for individuals at increased risk for severe disease (Box 53-6 ).
In the absence of an antimicrobial-susceptibility profile, empiric
therapy should be used.
Systemic infections should be treated with antimicrobial agents
based on the particular isolate's susceptibility profile.
Intravascular infections and osteomyelitis may require longterm antimicrobial therapy, possibly combined with surgery to
effect a cure.
Prevention
&
Control
(TMP/SMX)
Choice
orally
every
Adults
REFERENCES
Dupont HL: Shigella species (bacillary dysentery). In Mandell
GL et al: Principles and Practice of Infectious Diseases , 4th
ed. Churchill Livingstone, 1995.
Ericsson CD: Travelers' diarrhea: epidemiology, prevention,
and self-treatment. Infect Dis Clin North Am 1998; 12:285.
Miller SI, Hohmann EL, Pegues DA: Salmonella (including
Salmonella typhi ). In Mandell GL et al: Principles and
Practice of Infectious Diseases , 4th ed. Churchill
Livingstone, 1995.
Nataro JP, Kaper JB: Diarrheagenic Escherichia
Microbiol
Rev
coli. Clin
1998;11:142.
2001
McGraw-Hill
aeruginosa
54
Pseudomonas
aeruginosa
David Dockrell MD
Walter Wilson MD
Essentials
Nosocomial
of
Diagnosis
acquisition.
General
Considerations
and
staining
properties
microbiological
characteristics
microbiological
tests
aeruginosa
Clinical
Syndromes
PULMONARY
INFECTIONS
Infections
Primary pneumonia
Ventilator-associated
Bacteremic
pneumonia
pneumonia
Bacteremia
Bacteremia in association with neutropenia or AIDS
Nosocomial
Soft-Tissue
bacteremia
Infections
Ecthyma
gangrenosum
Burn wound sepsis
Hot tub folliculitis
Web space infection of the toe
Green nail syndrome
Urinary-Tract
Infection
Catheter-associated
Complicated
Ear
UTI
UTI
Infections
Otitis externa (swimmer's ear)
Malignant otitis externa
Chronic suppurative otitis media
Auricular perichondritis associated with ear piercing
Orthopedic
Infections
osteomyelitis
osteomyelitis
Sternoarticular
osteomyelitis
Symphysis pubis osteomyelitis
Endocarditis
Endocarditis in intravenous drug addicts
Prosthetic
valve
Ophthalmologic
endocarditis
Infection
Keratitis
Endophthalmitis
Central
Nervous
System
Infections
suppurative
focus
Gastrointestinal
Infections
bacteremia,
Meningitis,
osteomyelitis,
Syndrome
BOX 54-1 P
and
sinusitis
malignant
Major Clinical
Syndromes
otitis
externa
Other Clinical
Syndromes
INFECTIONS IN PATIENTS
CYSTIC
FIBROSIS
WITH
BACTEREMIA
P aeruginosa is a common cause of nosocomial bacteremia,
which may be either primary (no identifiable source) or
secondary (recognizable extravascular source). Communityacquired P aeruginosa bacteremia is very rare. Host factors
contributing to nosocomially acquired P aeruginosa bacteremia
include neutropenia caused by hematological malignancy or
host's
underlying
immunosuppression.
bacteremias.
erythema.
are
diagnostic.
Figure
54-3. Pseudomonas
URINARY
TRACT
INFECTION
ORTHOPEDIC
INFECTIONS
corticosteroids.
In addition, P aeruginosa prosthetic joint infections may occur
as a result of repeated surgical manipulation of the joint, joint
revision, or reimplantation of the prosthesis. Polymicrobial
osteomyelitis
with P aeruginosa and other microorganisms is
commonly associated with farm or motor vehicle accidents when
open fractures become contaminated with water, soil, or
vegetative materials. Vertebral osteomyelitis occurs in IV drug
abusers or as a complication of UTI or genitourinary surgery.
The lumbosacral spine is principally involved, although cervical
involvement occurs in IV drug abusers. Sternoarticular
pyarthrosis may occur in IV drug abusers or occasionally as a
complication of infective endocarditis. Infection of the
symphysis pubis may occur after pelvic or genitourinary surgery
and must be differentiated from nonpyogenic osteitis pubis.
Puncture wound infections of the foot occur at all ages and have
a particular association with punctures through rubber-soled
sneakers. These infections occur as a result of the growth of P
aeruginosa in the moist inner sole layer of the shoes, and
puncture wounds through the shoe inoculate P aeruginosa
directly into the bones of the foot and surrounding soft tissue.
Chronic osteomyelitis may occur as a result of contiguous
infection following trauma, surgery, or as a complication of
diabetic foot ulcers due to direct inoculation or local expansion
of the organism. These infections tend to be indolent with pain
and decreased range of movement in the absence of fever or
leukocytosis. An elevated erythrocyte sedimentation rate,
abnormalities on CT scanning or MRI or a positive radionuclide
scan suggest the diagnosis, but confirmation requires
demonstration of the organism on a Gram stain and recovery of
P aeruginosa from cultures. Puncture wounds of the foot may be
more acute in presentation, and typically the initial pain after
the injury resolves and recurs a few days later with pain and
swelling over the site of inoculation. Osteomyelitis of any of the
bones of the foot may result (Figure 54-4 ).
Effective
treatment
requires
antimicrobial
therapy
combined
and
antimicrobial
therapy.
ENDOCARDITIS
P
OPHTHALMOLOGIC
INFECTION
CENTRAL NERVOUS
INFECTION
SYSTEM
GASTROINTESTINAL
INFECTIONS
Diagnosis
The diagnosis of a P aeruginosa infection requires the
identification of the clinical syndrome by history, physical
examination, and laboratory testing. The specific syndrome
influences the duration of antimicrobial therapy and the need
for surgical intervention. In patients with positive blood
cultures, it is critical to determine the source of bacteremia.
Microbiological diagnosis requires the recovery of P aeruginosa
from culture. Gram-negative bacilli in culture should be
screened for the presence of oxidase. Oxidase production
excludes most
spp. Definitive
microbiological
Pseudomonas
Treatment
Antimicrobial therapy of P aeruginosa infections is outlined in
Box 54-2 . Resistance of P aeruginosa in vitro to many
antimicrobial agents is widespread and is increasing in
frequency. Susceptibility testing should be performed on all
clinically significant isolates to guide the selection of
appropriate antimicrobial therapy. In addition, the following
principles should be considered:
Antibiotics active in vitro against P aeruginosa often include
extended spectrum penicillins with or without the
combination of a -lactamase inhibitor; some thirdgeneration cephalosporins (ceftazidime, cefoperazone);
fourth-generation cephalosporins (cefepime); carbapenems
(imipenem, meropenem); monobactam (aztreonam);
aminoglycosides (gentamicin, tobramycin, amikacin,
netilmicin); and fluoroquinolones (for example
ciprofloxacin).
therapy
often
requires
surgical
intervention.
First
Choice
Alternative
Choice
Prevention
&
Control
PSEUDOMALLEI
MELIOIDOSIS
and
regional
lymphadenopathy.
MALLEI
(GLANDERS)
STENOTROPHOMONAS
MALTOPHILIA
BURKHOLDERIA
is
CEPACIA
P.580
REFERENCES
Arbulu A, Holmes RJ, Asfaw I: Surgical treatment of
intractable right-sided infective endocarditis in drug addicts:
25 years experience. J Heart Valve Dis 1993; 2:129.
Brewer SC, Wunderink RJ, Jones CB, Leeper KV: Ventilator
associated pneumonia due to Pseudomonas
aeruginosa.
Chest
1996;109:1019.
aeruginosa bacteremia in
2001
McGraw-Hill
pylori
55
Helicobacter
pylori
Essentials
of
Diagnosis
General
Considerations
of
P.582
and other bacteria. H pylori is identified by the formation of
pinpoint translucent colonies, its gram-negative staining
characteristics, and positive tests for oxidase, catalase, and
urease. Urease is produced in abundance by H pylori and is
the basis for two tests commonly used to diagnose H pylori
infection. Analysis of the complete H pylori genome reveals
a large number of genes that are predicted to encode ion
pumps, but few genes that encode regulatory factors; these
findings are consistent with the notion of an organism that
has adapted to a highly acidic environment.
Helicobacter
heilmannii is a related uncultivated
bacterium that is uncommon but appears also to be
associated with gastritis, peptic ulcer disease, and gastric
malignancy. Several other species of Helicobacter can
occasionally infect the large intestines and perhaps the
hepatobiliary system, and they are sometimes associated
with diarrheal disease.
Table
Condition
Strength
of
Association
Chronic histologic
gastritis
Causal relationship
established
Causal relationship
established for ulcers not
related to NSAIDs1 or to
Zollinger-Ellison
syndromes
Gastric
adenocarcinoma
Causal relationship
established; cofactors are
likely to be important
Gastric
lymphoma
Causal
relationship
established
Nonulcer
dyspepsia
Poor
Gastroesophageal
reflux (GERD)
Gastroesophageal
junction tumors
Cardiovascular
disease
Poor
1 NSAIDs,
anti-inflammatory
Nonsteroidal
drugs.
Pathogenesis.
Histopathology. All persons infected with H pylori have
a chronic gastritis characterized by mononuclear
inflammatory cells as well as an associated neutrophilic
infiltration. Both the organism and the gastritis tend to
be located preferentially in the gastric antrum. The role
of H pylori in causing this chronic gastritis, previously
thought to be a natural result of aging, has been clearly
demonstrated by the finding that eradication of H pylori
eliminates the gastritis and by two experimental selfinoculation studies in which physicians have voluntarily
ingested H pylori. The organism can be found
predominantly in the mucus gel layer, although a
minority of bacteria will be adherent to the gastric
epithelium. H pylori exhibits a profound tissue tropism,
and it attaches only to gastric epithelium in the stomach
or to epithelium in the proximal duodenum that has
undergone
gastric
metaplasia.
and
virulence
factor.
Clinical
Acute
gastric
cancer.
Findings
Infection. Limited human inoculation studies suggest
tissue (MALT)
strongly associated with
the tumor can be cured
75% of patients.
Diagnosis
Several methods for diagnosis of H pylori are available, both
Table
pylori.
Advantages
Disadvantages1
Serum
ELISA
Inexpensive
Urea
test
Useful for
follow-up
Expensive; may
be falsely
negative in
patients on acid
suppression
Non
invasive
breath
therapy
Stool
antigen test
Inexpensive;
useful for
follow-up
Inconvenient
Whole
assay
Inexpensive;
rapid
Less accurate
than serum ELISA
Visualization
of pathology
Rapid
May be falsely
positive in
bacterial
overgrowth
Antibiotic
susceptibility
Not maximally
sensitive; not
blood
Invasive
(endoscopic)
Histology
Rapid
urease
Culture
available
routinely;
requires 47 d
1 ELISA,
Enzyme-linked
immunosorbent
assay.
Treatment
Indications for Antibiotic Therapy. All patients with
peptic ulcer disease and H pylori infection should be treated
with antibiotics, unless an alternative cause such as NSAIDs
can be clearly demonstrated. This includes patients newly
presenting with ulcer disease as well as those with a welldocumented history of ulcer. Often these latter patients will
be intermittently taking H2 blockers or proton pump
inhibitors, which can be stopped after effective antibiotic
therapy. Patients with MALT lymphoma should also receive
antibiotic treatment for H pylori. Cost-benefit analyses have
suggested that it may be economical to treat empirically
patients who have dyspepsia and H pylori infection.
However, the now documented failure of H pylori therapy to
ameliorate the symptoms of nonulcer dyspepsia, together
with growing problems with antibiotic resistance, renders
this strategy less attractive. Furthermore, controversial data
suggest that eradication of H pylori may be associated with
an increased incidence of gastroesophageal reflux disease
(GERD) and carcinoma of the gastroesophageal junction.
Preventive antibiotic therapy may also be considered in a
patient with H pylori infection and a family history of gastric
adenocarcinoma. Because long-term therapy with acid
suppression in H pylori-infected patients with GERD has
sometimes been associated with increased risk of atrophic
gastritis, some have suggested that these patients receive
therapy for H pylori to prevent gastric cancer. This remains
controversial, particularly in light of the evidence that H
pylori eradication may exacerbate symptoms of GERD. H
pylori screening and treatment in patients with no
symptoms and no risk factors for gastric cancer are not
indicated based on current data.
Antibiotic
Regimens. Several general guidelines are
helpful to identify a proper treatment regimen. First, results
Table
Drug
Dose
Frequency
As
directed
2 Times
daily
Bismuth
2 tablets
4 Times
subsalicylate
daily
Tetracycline
500 mg
orally
3 Times
daily
Metronidazole
500 mg
orally
3 Times
daily
As
directed
1 g orally
500 mg
2 Times
daily
2 Times
daily
orally
500 mg
orally
2 Times
daily
2 Times
daily
Amoxicillin
Clarithromycin
Metronidazole
1 Ranitidine
Prevention
&
Control
REFERENCES
Blaser MJ: Hypothesis: the changing relationships of
Helicobacter
pylori and humans; implications for health and
disease. J Infect Dis 1999;179:1523.
Dunn BE, Cohen H, Blaser MJ: Helicobacter
Microbiol
Rev
pylori. Clin
1997;10:720.
pylori. Curr
2001
McGraw-Hill
Bordetella,
&
Branhamella
Species
56
Haemophilus,
Branhamella
Bordetella,
Species
&
HAEMOPHILUS
HAEMOPHILUS
Essentials
of
Haemophilus
influenzae is generally acquired via the aerosol
route or by direct contact with respiratory secretions.
The most common associated syndromes include otitis media,
sinusitis, conjunctivitis, bronchitis, pneumonia, and, to a
lesser extent, meningitis, epiglottitis, arthritis, and cellulitis.
Gram
stain
shows
pleomorphic
gram-negative
coccobacilli.
General
Considerations
in
undervaccinated
children.
influenzae sepsis,
immunity.
H influenzae
+
+
+
H parainfluenzae1
+
H
+
+
H
aphrophilus
paraphrophilus1
+
H haemolyticus
+
+
+
+
H parahaemolyticus
-
+
+
+
H segnis1
+
H ducreyi
+
+
+
1
ferments
neither
Growth
Organism
Factor
Hemolysis
Requirement
Catalase
C O2
Dependence
CLINICAL
SYNDROMES
1.
MENINGITIS
Clinical
Findings
Meningitis
Irritability
Lethargy
Photophobia
Stiff neck
Epiglottitis
Sore throat
Dysphagia
Dyspnea
Drooling
Pyogenic
Arthritis
Joint pain
Swelling
Decreased range of motion
Cellulitis
Skin erythema (sometimes with violaceous hue)
Warmth
Tenderness
Otitis
Media
Ear pain
Bulging tympanic membrane with distorted landmarks and
decreased mobility
Sinusitis
Nasal discharge
Fever
Cough
Headache
Facial tenderness
Pneumonia
Cough
Tachypnea
Crackles on
auscultation
For all H
Disease
2.
EPIGLOTTITIS
Clinical
Findings
3.
PNEUMONIA
Clinical
Findings
Generally, H
influenzae
P.591
4.
PYOGENIC
ARTHRITIS
Clinical
Findings
5.
CELLULITIS
Clinical
Findings
organism.
Complications. Related to the fact that bacteremia is
generally present, ~ 10% of children develop another focus
of infection, for example, meningitis. H influenzae is not
associated with cellulitis that occurs as a complication of
trauma to the skin.
6.
OTITIS
MEDIA
Clinical
Findings
7.
SINUSITIS
8. EXACERBATIONS
LUNG DISEASE
OF
UNDERLYING
9.
NEONATAL
SEPSIS
Clinical
Findings
10.
BRAZILIAN
Clinical
PURPURIC
FEVER
Findings
11.
CHANCROID
Clinical
Findings
or
others
Other diagnostics
Assay for type-b antigen in sterile body fluids
Direct immunofluorescence or polymerase chain
assay
None
reaction
Serology
Available, generally not useful
Moderately useful
Not
available
H
influenzae
pertussis
catarrhalis
Diagnosis
Consideration of the diagnosis of meningitis, epiglottitis,
pneumonia, pyogenic arthritis, or cellulitis is usually prompted by
the history and physical examination (Table 56-2 ). In most
cases of invasive H influenzae type-b disease, blood cultures are
positive. H influenzae is often cultivated from samples of pleural
fluid, joint fluid, or pericardial fluid in affected patients.
Choice
Cefotaxime or
Ceftriaxone
150200 mg/kg/d divided every 8 h
50100 mg/kg/d divided every 12 h
12 g every 48 h
2 g every 12 h
Second
Choice
Ampicillin, if susceptible, or
Chloramphenicol
if
susceptible
Therapy
(for
Meningitis)
Dexamethasone
0.6 mg/kg/d divided every 6 h for 4 d or
Children
Adults
Treatment
Empiric therapy for invasive disease caused by H influenzae
generally includes either a third-generation cephalosporin, such
as cefotaxime or ceftriaxone, or the combination of ampicillin
and chloramphenicol (Box 56-2 ). In the United States, ~ 30% of
H influenzae isolates are resistant to ampicillin, and thus
ampicillin should never be used alone as empiric therapy.
Ampicillin resistance usually is related to plasmid-mediated
production of -lactamase, but occasionally is caused by
decreased affinity of certain penicillin-binding proteins. To
distinguish one form of resistance from the other, both disk
susceptibility testing and a -lactamase assay should be
performed. Chloramphenicol is bactericidal for H influenzae and
reliably penetrates into the CSF. Although resistance to
chloramphenicol has been reported, it remains rare in the United
States, especially among invasive isolates.
In recent years, the third-generation cephalosporins have
become the treatment of choice for H influenzae meningitis. Both
cefotaxime and ceftriaxone have potent activity against H
influenzae (including ampicillin-resistant isolates) and achieve
high levels in the CSF. For patients with uncomplicated
meningitis, therapy for 710 days is adequate. For patients
who fail to respond promptly or develop complications, therapy
for > 10 days may be necessary. Based on empiric experience,
most experts recommend that other invasive infections caused
by H influenzae also be treated with an appropriate parenteral
antibiotic for 710 days.
Choice
Amoxicillin,
if
susceptible
Choice
Amoxicillin
plus
clavulanate
(Augmentin)
sulfamethoxazole
component)
(TMP-SMX)
second
and
third-generation
cephalosporins
sulfisoxazole
available.
Medication
Children
Adults
Prevention
&
Control
Measures
Precautions
strains.
HbOC
HibTITER
Small
None
CRM197 mutant Corynebacterium
PRP-T
diphtheriae toxin
ActHIB
OmniHIB
Large
6-Carbon
Tetanus toxoid
PRP-OMP
PedvaxHIB
Medium
Thioether
N meningitidis outer membrane protein complex
PRP-D1
ProHIbiT
Medium
6-Carbon
Diphtheria toxoid
1 PRP-D is licensed for children 12 months old. The other
three vaccines are licensed for use in infants.
Vaccine
Table
Trade
Name
Polysaccharide
Linkage
Protein
carrier
56-3. Haemophilus
influenzae type b conjugate
vaccines licensed for use in children.
individuals at
colonization
hosts. In
case and all
BORDETELLA
SPECIES
Essentials
Diagnosis
of
General
Considerations
Epidemiology. Bordetella
pertussis is a respiratory
pathogen with a tropism for ciliated respiratory epithelial
cells and is the usual cause of an acute respiratory infection
called pertussis or whooping cough, which was described as
far back as 1500. B parapertussis accounts for ~ 5% of cases
of pertussis in the United States and typically produces more
mild disease. The term pertussis means intense
cough, reflecting the most striking feature of the illness.
Pertussis is a common disease worldwide, with ~60 million
cases and > 500,000 deaths each year. During the
prevaccine era in the United States, pertussis was the
leading cause of death from a communicable disease among
children < 14 years, and in 1945, pertussis caused more
deaths in infants in the United States than did diphtheria,
B pertussis
+
B
+
+
B
+
+
+
+
parapertussis
bronchiseptica
+
B hinzii1
+
+
+
B holmesii1
1
Organism
Table
Motility
Oxidase
Urease
Utilizes
Citrate
Reduces
Nitrate
CLINICAL
SYNDROME
Clinical
Findings
Catarrhal
Stage
Low-grade fever
Rhinorrhea
Mild cough
Paroxysmal
Stage
Stage
pertussis Disease
Diagnosis
The traditional approach for diagnosing pertussis involves
culturing B pertussis or B parapertussis from nasopharyngeal
mucus (see Table 56-2 ). Mucus should be collected by aspiration
or by swabbing the nasopharynx with a dacron or calcium
alginate swab. After plating on an appropriate medium, B
Treatment
Infants < 6 months and other patients with potentially severe
disease often require hospitalization for supportive care to
manage coughing paroxysms, apnea, cyanosis, feeding
difficulties, and other complications. Antibiotic therapy initiated
during the catarrhal stage promotes more rapid clinical
improvement (Box 56-6 ). However, after the onset of
paroxysms, antimicrobial agents usually have little discernible
effect on the course of illness. Nevertheless, they are
recommended to limit the spread of the organism to others. The
drug of choice is erythromycin. Currently, the recommended
duration of therapy is 14 days, although recent evidence
suggests that a 7-day course is also efficacious. Azithromycin
and clarithromycin are alternatives based on clinical studies
demonstrating the ability of these drugs to eradicate the
organism.
Trimethoprim/sulfamethoxazole
is
another
possible
P.599
Choice
Choice
albuterol,
and
pertussis-specific
immunoglobulin
Prevention
&
Control
erythromycin
or
alternative
Isolation
Precautions
Droplet precautions for first 5 d of treatment
BOX 56-7 Control of B
pertussis Infection
BRANHAMELLA
Essentials
of
CATARRHALIS
Diagnosis
Branhamella
catarrhalis is presumed to be acquired by direct
contact with contaminated respiratory tract secretions or by
droplet spread.
The most common infections include otitis media, sinusitis,
and, to a lesser extent, exacerbations of underlying lung
disease.
Gram stain of infected fluid shows gram-negative diplococci.
Culture of infected fluids when indicated is also useful.
General
Considerations
CLINICAL
SYNDROMES
Media
Ear pain
Fever
Bulging tympanic membrane with distorted landmarks and
decreased
mobility
Sinusitis
Nasal discharge
Fever
Cough
Headache
Facial tenderness
Exacerbation of Lung Disease
Increased dyspnea
Fever
Sputum production
Sputum purulence
BOX 56-8 Clinical Manifestations of B catarrhalis Disease
P.601
Clinical
Findings
Diagnosis
Tympanocentesis is necessary to establish the etiology of otitis
media, and sinus aspiration is required
P.602
to confirm the cause of sinusitis (see Table 56-2 ). However,
these procedures are rarely performed. In patients with
pneumonia, auscultation sometimes reveals evidence of
consolidation, and chest radiograph sometimes shows patchy or
lobar infiltrates. Pleural effusion and empyema are uncommon.
The most practical approach to establish the diagnosis of B
catarrhalis pneumonia or bronchitis is to examine a gram-stained
sputum sample, which will show a predominance of intracellular
and extracellular gram-negative diplococci.
Amoxicillin
plus
clavulanate
(Augmentin)
sulfamethoxazole
(TMP-SMX)
second
and
third-generation
cephalosporins
sulfisoxazole
available.
Medication
Children
Adults
catarrhalis Disease
Treatment
Approximately 80% of isolates produce -lactamase, and at
least three different B catarrhalis -lactamases have been
identified, including BRO-1, BRO-2, and BRO-3. The activity of
these -lactamases can be inhibited by -lactamase inhibitors
such as clavulanate and sulbactam. Most B catarrhalis infections
can be treated with oral agents, including Augmentin (amoxicillin
plus
clavulanate),
erythromycin,
trimethoprim-sulfamethoxazole,
and tetracycline (Box 56-9 ). B catarrhalis is also uniformly
susceptible to ticarcillin, piperacillin, mezlocillin, azlocillin, most
second- and third-generation cephalosporins, chloramphenicol,
Prevention
&
Control
REFERENCES
Catlin BW: Branhamella
catarrhalis : an organism gaining
respect as a pathogen. Clin Microbiol Rev 1990; 3:293.
Centers for Disease Control and Prevention: 1998 Guidelines
for Treatment of Sexually Transmitted Diseases. MMWR
1998;47:18.
Centers for Disease Control and Prevention: Pertussis
vaccination: use of acellular pertussis vaccines among infants
and young children. MMWR 1997;46:1.
Centers for Disease Control and Prevention: Progress toward
elimination of Haemophilus
influenzae type b disease among
infants and childrenUnited States, 19871995. MMWR
1996;45:901.
1989;2:137.
Microbiology,
1994:157.
2001
McGraw-Hill
&
Campylobacter
57
Vibrio
&
Campylobacter
Gary W. Procop MD
Frank R. Cockerill III MD
VIBRIO
INFECTIONS
VIBRIO
CHOLERAE
Essentials
of
INFECTIONS
Diagnosis
General
Considerations
The areas where cholera remains endemic lack adequate sewage disposa
systems and water treatment facilities. Cholera epidemics often occur
during war, when basic human needs are not met. Throughout the past
30 years, cholera epidemics have repeatedly occurred in overcrowded
refugee camps. In the 1994 Rwandan refugee camps, a significant
proportion of the deaths were caused by cholera. During this time,
600,000 people are believed to have been infected with V cholerae 01,
which resulted in ~ 45,000 deaths.
CLINICAL
SYNDROMES
Clinical
Findings
Laboratory
Findings. The stool from patients with cholera tends to lose
its fecal odor as the disease progresses and may develop a sweet odor.
Also, as the disease progresses and normal fecal material is passed, the
stool becomes watery, turbid, and gray. Small flecks of mucus in this
gray water give these stools their rice water appearance. Blood
and neutrophils are generally not present in choleric stools. In the
appropriate clinical and epidemiological context (eg, during outbreaks of
cholera), a direct examination of stool can be useful for the presumptive
identification of V cholerae. A microscopic examination of stool that
discloses straight or curved bacilli with rapid, darting, or shooting
star motility is suggestive of V cholerae. Inhibition of the motility of
the organism by V cholerae O1 antiserum further supports the diagnosis
of cholera.
Differential
Diagnosis. Salmonella species, Shigella species, Yersinia
enterocolitica,
Campylobacter species, and the enteric pathogenic E coli;
viruses such as rotavirus and Norwalk agent; and parasites, such as
Giardia lamblia and species of Cyclospora and Cryptosporidium are
common pathogens that should be considered in the differential
diagnosis of diarrheal disease. The diagnosis of these pathogens is
achieved by a careful history combined with laboratory testing.
Complications. Profound dehydration and hypoglycemia may result in
altered mental status, unconsciousness, seizures, and renal failure.
Electrolyte abnormalities may manifest as muscle weakness, intestinal
ileus, or sudden death caused by cardiac arrhythmia. Vomiting
exacerbates the dehydration, makes oral rehydration difficult, and may
More
Common
Common
Ileus
BOX 57-1 Clinical Syndromes of Cholera
Treatment
Primary Therapy. Primary therapy of cholera consists of fluid and
electrolyte replacement. Published guidelines for fluid and electrolyte
replacement in cholera are available. Either a citrate (10 mmol/L)- or
bicarbonate (30 mmol/L)-based solution may be used for oral
rehydration. These should contain sodium (90 mmol/L), potassium (20
mmol/L), chloride (80 mmol/L), and glucose (111 mmol/L). The glucose
is actively transported into enterocytes. This osmotically drives water
from the lumen and into the body. In developing countries, the water
residua from boiled rice may be used for rehydration. This is an
Antimicrobial
Therapy. Treatment with tetracycline will shorten the
duration of cholera (Box 57-2 ). Pregnant women and children who
develop cholera should be treated with ampicillin. If allergies to penicilli
exist, trimethoprim-sulfamethoxazole and furazolidone are also effective
Prognosis
The prognosis for patients infected during cholera epidemics is often poor.
This directly parallels the lack of basic medical care, such as fluid and
electrolyte replacement, which exists in the situations that foster epidemic
cholera. If patients with cholera are given appropriate fluid, electrolyte, and
glucose replacements, the prognosis is good. In many instances, the fluid
replacement is roughly based on the volume lost. Patients who are not
recognized to have an intestinal ileus may fare poorly. These patients may
initially be misdiagnosed or if recognized to have cholera may not receive
adequate fluid and electrolyte replacement.
Prevention
&
Control
A clean water supply and effective sanitation are essential for preventing
epidemic cholera. The economic means for effective waste disposal and
preventive healthcare are not available to the impoverished; therefore
cholera persists. In sporadic cases, patient isolation with appropriate waste
disposal and hand washing are important means of preventing the spread of
disease.
Two vaccines are currently being studied for high-risk individuals to use.
These are a B-subunit, killed whole-cell vaccine (BC-WC) and a live,
OTHER V IBRIO
Essentials
of
INFECTIONS
Diagnosis
General
Considerations
reactions necessary to separate the vibrios into these six groups include
the following: (1) the requirement of NaCl for growth in nutrient broth;
(2) oxidase production; (3) nitrate reductive capacity; (4) myo -inositol
fermentation; and (5) the presence or absence of arginine dehydrolase,
lysine decarboxylase, and ornithine decarboxylase. Additional
biochemical reactions may be used for complete speciation.
These tests are used in the microbiology laboratory to exclude certain
diagnostic possibilities. Most vibrios are oxidase positive, with the
exception of V metschnikovii. With the exception of V cholerae and V
mimicus , isolates require 1% NaCl supplementation to adequately
perform biochemical tests. The six groups are as follows:
Group 1 consists of V cholerae and V mimicus. These are readily
distinguished from the other vibrios by their ability to grow in nutrient
broth, without NaCl supplementation.
Group 2 consists of V metschnikovii , which is differentiated from other
vibrios by its inability to produce oxidase and reduce nitrate to nitrite.
Group 6 consists of V
alginolyticus,
parahaemolyticus,
P.607
V vulnificus , and V carchariae. These organisms are differentiated from
other vibrios by a combination of their ability to produce lysine
decarboxylase and their inability to hydrolyze arginine.
Children 1
Adults
First Choice
Ampicillin, 250 mg orallyor IV every 6 h for 5 d
Tetracycline, 250 mg orally or IV every 6 h for 5 d
During pregnancy, ampicillin is the drug of choice (dosage as below)
Second
Choice
Allergic
Tetracycline and the quinolones are generally not given to children becaus
Fluid
and
Consideration
Electrolyte
Replacement,
Acid-Base,
CLINICAL
SYNDROMES
Noncholera vibrios cause both enteritis and extraintestinal disease (Box 57-3
). In the United States, Vibrio species other than V cholerae are far more
common causes of Vibrio -associated gastroenteritis. These agents include V
parahaemolyticus, V mimicus, V hollisae , and others. The enteritis caused
by these
pain and
Many of
enhances
undercooked
shellfish. V parahaemolyticus is the most common cause of
shellfish-associated gastroenteritis in the United States. In most instances,
the enteritis is self-limited, but complications may occur. Septicemia with
severe morbidity and death has occurred following noncholera Vibrio
gastroenteritis.
Enteric
Disease
Disease
condition
NONCHOLERA
Clinical
GASTROENTERITIS
Findings
usually less severe than those present in cholera but may become
profound in children and the elderly. Culture and biochemical
identification of the isolate is the standard method of establishing the
etiologic agent of disease. The key biochemical reactions for rapidly
subcategorizing Vibrio species are listed in the Microbiology section.
Many of the group characteristics are based on an organism's ability to
perform particular biochemical tests. Therefore it is important to
P.608
EXTRAINTESTINAL
Clinical
DISEASE
Findings
Laboratory
Findings. Hematopoietic findings are variable and may
demonstrate either leukocytosis or leukopenia with left-shifted
hematopoiesis. The isolation of vibrios from patients with extraintestinal
disease is usually not difficult. The selective and differential agars are
not required since the sites of culture are normally sterile. Vibrios
causing extraintestinal disease are usually isolated on routine 5%
sheep's blood agar. If an extraintestinal Vibrio infection is suspected, th
microbiology laboratory should be notified. The supplementation of
media with 1% NaCl may aid in the more rapid identification of the Vibri
species.
Imaging. Ultrasound or computerized tomography guidance may be
useful for identifying and assisting in drainage of deep abscesses.
Differential
Diagnosis. Improperly cared for wounds may be colonized
and infected by a variety of bacteria. When these wounds have been
exposed to salt water or the patient has recently eaten raw or
undercooked shellfish, a vibrio infection should be considered.
Although immunocompromised patients may be infected by a variety of
microbes, an extraintestinal vibrio infection should be considered when
skin lesions and a sepsislike syndrome are present in association with
the recent ingestion of raw or undercooked shellfish.
Treatment
Prognosis
Prevention
&
Control
the hazards, raw oysters and clams remain popular in many parts of the
world. Warnings concerning the possible health hazards
P.609
should be posted in plain view in restaurants that serve these dishes, and
additional caution should be directed specifically to individuals with liver
disease or other immunocompromising conditions. Individuals with healing
wounds should avoid exposing the wounds to seawater.
First
Choice
Choice
Allergic
Adults
Infections
Measures
Precautions
CAMPYLOBACTER
Essentials
of
Infections
INFECTIONS
Diagnosis
thrombophlebitis,
endocarditis,
42C.
P.610
General
Considerations
In developed countries, the carriage rate is very low (< 1%). This may
result from more effective treatment of human waste, requisite
pasteurization of dairy products, and educational efforts regarding the
thorough cooking of meat products. In developed countries,
campylobacteriosis tends to occur sporadically and year round, with pea
incidence in months of the spring or fall. In many instances, infections
can be linked to the ingestion of undercooked meats, contaminated milk,
or contaminated water supplies.
Like Salmonella,
Campylobacter organisms are susceptible to
hydrochloric acid. Entry with foods that buffer stomach acid is important
for gastric passage of viable organisms. C jejuni thrives in the small
intestine and colon and is able to replicate in human bile. Infection is
initiated by adhesion and colonization. Bacterial proteins that are
important for this phase of infection include the superficial bacterial
antigen PEB1, and possibly the newly characterized periplasmic binding
protein P29. Peritrichous, piluslike structures that are present only when
the organism is grown in the presence of bile, may also aid in adhesion.
Motility and the adhesion properties of the flagellar protein flagellin are
Common
malaise,
Common
and
Pericarditis
Cellulitis
Salpingitis
Reiter's syndrome
Meningoencephalitis
Septic arthritis
Spontaneous bacterial
Guillain-Barr
Osteomyelitis
Empyema
Intestinal
peritonitis
syndrome
(C jejuni )
Extraintestinal
(C fetus )
CAMPYLOBACTER
Clinical
ENTERITIS
Findings
Laboratory
Findings. Direct examination of stool specimens often
demonstrate curved, vibriolike rods with a characteristic darting motility
Leukocytes are present in 75% of patients with Campylobacter enteritis.
Culture on selective media with incubation at 42C, in a microaerophilic
environment, is used for the enhanced detection of most of the
enteropathic Campylobacter species (Figure 57-2 ). The most common
causes of Campylobacter enteritis, C jejuni and C coli , both grow well a
More
Common
C jejuni
C coli
C fetus
+
-
+
+
+
Variable
Susceptible
Variable
Resistant
Resistant
Susceptible
Less
Common
C
C
upsaliensis
hyointestinalis
+
+
+
Susceptible
Resistant
Susceptible
Susceptible
Growth at
Species
Table
Hippurate
Hydrolysis
25C
42C
Susceptibility
to
Nalidixic
Acid
Cephalothin
EXTRAINTESTINAL
Clinical
CAMPYLOBACTERIOSIS
Findings
Differential
Diagnosis
Complications
the
immunogenic
stimulus.
Treatment
Choice
Choice
Adults
Prognosis
Severe dehydration and electrolyte imbalances may cause death. This most
frequently occurs in children, particularly in underdeveloped and
Measures
Prevention
Pasteurization, washing foods when feasible, thorough cooking, and hand
REFERENCES
Blaser
Principles
of
Internal
2001
McGraw-Hill
58
Legionella
Michael Bell MD
Essentials
of
Diagnosis
General
Considerations
(especially
hot-water)
distribution
systems
are
host
CLINICAL
defense.
SYNDROMES
1.
PONTIAC
FEVER
Common
Pneumonia
Self limited, acute flulike illness characterized by malaise,
myalgia, fever, chills, and headache
Less
Common
cough,
nausea
Pontiac
Fever
2.
LEGIONNAIRES'
DISEASE
Diagnosis
Diagnosis
Treatment
Erythromycin is the recommended treatment for Legionnaires'
disease and other serious Legionella infections; however, failures
have occurred, and adverse effects are common (Box 58-2 ).
Erythromycins, intravenous azithromycin, and levofloxacin are
currently approved by the US Food and Drug Administration for
treatment of Legionnaires' disease. Although prospective controlled
comparisons have not been performed, clarithromycin and quinolone
antibiotics are also effective. Other agents with activity against
Legionellaceae include doxycycline, minocycline, rifampin, and
trimethoprim-sulfamethoxazole. For severe illness and for treatment
of immunosuppressed patients, combination treatment either with
rifampin plus a macrolide or quinolone or with a quinolone plus a
macrolide (eg, levofloxacin plus azithromycin) is recommended.
Prevention
&
Control
Choice
Choice
for
Immunosuppressed
Patients1
Children
Isolation
Requirements
None indicated. No evidence of person-to-person transmission
Environmental
Control
In hospitals with a significant immunocompromised population,
superheating and flushing of water supplies identified as
reservoirs of L pneumophila has been attempted with variable
success.
Adjunctive use of copper-silver ionization and ultraviolet
systems has been reported effective. Hyperchlorination is no
longer
recommended.
Drain, scrub, and disinfect water reservoirs; periodic
maintenance treatment required.
BOX 58-3 Prevention and Control of Legionella
Infection
REFERENCES
1996;347:494.
Kaufmann AF et al: Pontiac fever: isolation of the etiologic agent
(Legionella
pneumophila ) and demonstration of its mode of
transmission. Am J Epidemiol 1981;114:337.
Keller DW et al: Community outbreak of Legionnaires' disease:
an investigation confirming the potential for cooling towers to
transmit Legionella species. Clin Infect Dis 1996;22:257.
Klein NC, Cunha BA: Treatment of Legionnaires' disease. Semin
Respir Infect 1998;13:140.
Koide M et al: Relation between the polymerase chain reaction
and the indirect fluorescent antibody method in thediagnosis of
Legionella infection. Clin Infect Dis 1996;23:656Lin YS et al:
Disinfection of water distribution systems for Legionella. Semin
Respir Infect 1998;13:147.
Liu Z et al: Intermittent use of copper-silver ionization for
Legionella control in water distribution systems: a potential
option in buildings housing individuals at low risk of infection.
Clin Infect Dis 1998;26:138.
Rutledge
(APACHE
unit: an
in 1,238
2001
McGraw-Hill
Anaerobes
59
Important
Anaerobes
Jorge Villacian MD
James Steckelberg MD
Essentials
of
Diagnosis
of
septic
thrombophlebitis.
with
malignancies
(especially
intestinal).
General
Considerations
tract: Fusobacterium
nucleatum,
fragilis,
Prevotella
melaninogenica , and Peptostreptococcus spp.
are the most common anaerobic organisms in this site.
Female genital tract: Lactobacillus spp., the
predominant species in this location, protect against
bacterial
vaginosis.
Microbial
Factors:
promote
tissue
destruction.
forming:
Clostridium
C tetani
C difficile
botulinum
C septicum
C ramosum
Nonspore forming:
Propionibacterium spp.
Lactobacillus spp.
Bifidobacterium spp.
Actinomyces spp.
Microaerophilic
streptococci
Peptococcus niger
Prevotella
melaninogenica
Peptostreptococcus spp
B fragilis
Porphyromona spp
Prevotella
melaninogenica
Fusobacterium
nucleatum
F necrophorum
Veillonella spp.
GramPositive
Bacilli
Table
GramPositive
Cocci
GramNegative
Bacilli
GramNegative
Cocci
Host
anaerobes.
Factors:
Iatrogenic
Factors:
of
broad-spectrum
antimicrobial
agents
alters
CLINICAL
SYNDROMES
fragilis group
Porphyromonas spp.
Prevotella spp.
Peptostreptococcus spp.
Fusobacterium spp.
Necrophorum spp.
Central
Nervous
System
Brain abscess
Subdural empyema
Epidural abscess
B fragilis group
Peptostreptococcus spp.
Fusobacterium spp.
Prevotella spp.
Actinomyces spp.
Microaerophilic
streptococcus
Respiratory
Tract
Aspiration
Empyema
pneumonitis
B fragilis group
Prevotella
melaninogenica
Bacteroides spp.
Peptostreptococcus spp.
Fusobacterium spp.
Clostridia
Veillonella spp.
Intra-abdominal
Peritonitis
Intra-abdominal
abscess
Appendicitis
Pyogenic liver abscess
Postsurgical wound infections
Enteritis
necroticans
Neutropenic
enterocolitis
Bacteroides spp.
Peptostreptococcus spp.
Fusobacterium spp.
Lactobacillus spp.
Eubacterium spp.
Clostridia
Female Genital Tract
Endometritis
Amnionitis
Septic abortion
Postsurgical wound infections
Pelvic inflammatory disease
IUD-related bacterial vaginosis
Peptostreptococcus spp.
Prevotella spp.
Porphyromonas spp.
Clostridia
Actinomyces spp.
Eubacterum nodatum
Skin, Soft Tissue, and Bone Infections
Bite wound infections
Diabetic foot infections
Infected decubitus ulcers
Burn wound infections
Paronychia
Breast abscess
Infected sebaceous and pilonidal cysts
Anaerobic
cellulitis
Necrotizing
fasciitis
Myonecrosis (gas gangrene)
Chronic
osteomyelitis
B fragilis group
Fusobacterium spp.
Prevotella spp.
Porphyromonas spp.
Clostridia
Peptostreptococcus spp.
Toxin-Mediated
Clostridial
Botulism
Tetanus
Antibiotic-associated
Clostridium
C tetani
C difficile
Site
Clinical
Diseases
pseudomembranous
colitis
botulinium
Syndrome
Anaerobe
Involved
2. ORAL CAVITY
This site is heavily colonized with anaerobes. Consequently,
many infections involving oral cavity structures as well as the
pharyngeal spaces involve anaerobic bacteria.
Clinical
Findings
3.
PHARYNGEAL
Clinical
SPACES
Findings
CENTRAL
NERVOUS
SYSTEM
Clinical
Findings
staphylococci,
streptococci,
and
gram-negative
bacilli.
RESPIRATORY
TRACT
Clinical
Findings
performed.
INTRA-ABDOMINAL
The gastrointestinal tract harbors a rich microbial flora, and any
process that involves perforation or manipulation of a hollow
viscus could potentially result in the translocation of bacteria
into normally sterile sites. In the oral cavity, there are 107
108 anaerobes/mL of oral contents; the proportion is
101000/mL in the stomach, 104 106 anaerobes/mL in the
terminal ileum, and 1011 /g of stool in the colon.
1.
BOWEL
FEMALE
GENITAL
TRACT
Clinical
Findings
thrombophlebitis.
Laboratory
Findings. The diagnosis of bacterial vaginosis
is suggested by secretions with a pH
P.625
of > 4.5, a fishy odor when treated with 10%
hydrogen peroxide, and visualization of clue cells.
Clinical
Findings
reflect
overwhelming
infection.
Laboratory
Findings. Microbiologic diagnosis is difficult
and superficial swabs are usually not helpful. Deep tissue
specimens obtained surgically are preferred in severe cases
or when prolonged therapy is anticipated. The organisms
that are most frequently encountered in diabetic foot and
decubitus ulcer infections include B fragilis, Fusobacterium
spp., Prevotella
melaninogenica,
Porphyromonas,
Peptostreptococcus , and members of the Clostridium genus.
Gas gangrene is associated with C perfringens and C
septicum. Necrotizing fasciitis involves Bacteroides spp. as
well as clostridia.
BACTEREMIA
Anaerobes cause from 5 to 10% of all bacteremias. B fragilis
and related species account for 6080% of all cases, followed
by clostridia and peptostreptococci. Organisms such as
Propionibacterium usually represent contamination of blood
Clinical
Findings
OSTEOMYELITIS
It is not uncommon to find anaerobes in cases in which the
predisposing factor is vascular insufficiency as in diabetic foot
ulcers. Other examples are skull or facial bone infections arising
from chronic otitis media, sinusitis, or mastoiditis. Clinically,
these infections tend to run indolent courses and may
occasionally present with foul smelling drainage through sinus
tracts. Gram-negative bacilli and peptostreptococci are
frequently
involved.
TOXIN-MEDIATED
1.
INFECTIONS
TETANUS
stimuli.
Clinical
Findings
Bacilli
First
Choice
Alternatives
Comments
Diagnosis
Diagnosis of tetanus is made clinically; conditions that might
have similar features are strychnine poisoning and dystonic
reactions.
Treatment
Treatment should be supportive. Sedation is important:
benzodiazepines, propofol, and in severe cases, paralyzing
agents can be used; the role of antibiotics is controversial (see
Box 59-2 ). When autonomic dysfunction is present, alpha and
beta adrenergic blocking agents are recommended.
2.
BOTULISM
Clinical
Findings
ophthalmoplegia,
and
respiratory
failure.
Laboratory
Findings. Besides clinical findings and careful
history, stool and serum toxin assays help establish the
diagnosis.
Differential
Diagnosis. Differential diagnosis of botulism
includes myasthenia gravis, Lambert-Eaton paraneoplastic
syndrome, and Guillain-Barr syndrome.
Treatment
Treatment is mainly supportive; antitoxin made from equine
serum can be used. In the United States, it is obtained through
state health departments or the Centers for Disease Control.
The standard dose is one vial intravenously and one vial
intermittently. It may be repeated every 4 h in severe
progressive cases. Clinical trials evaluating its efficacy are
lacking. Full recovery takes from 3 months to 1 year. Risk of
death ranges from 4 to 25%, depending on the promptness with
which the diagnosis is made.
3.
ANTIBIOTIC-ASSOCIATED
COLITIS
Clostridium
difficile is the principal causative agent of antibioticassociated colitis. Two types of toxin are produced by C difficile
: (1) an enterotoxin (the most important in its pathogenesis)
and (2) an enterotoxin that is cytophatic. This organism is
present in the bowel flora of 50% of neonates. This rate
declines to 4% by age 2 years. However, antibiotic treatment
and hospitalization have been proven to increase the carriage
rate 46%. Chemotherapeutic agents (for malignancies)
and antibiotics (most commonly ampicillin, clindamycin, and the
cephalosporins) are associated with C difficile
pseudomembranous colitis. Bowel stasis and surgery predispose
to this disease as well, although, in some cases, no identifiable
risk factor is found.
Clinical
Findings
Treatment
In treating patients who have C difficile
pseudomembranous colitis, if possible, an
narrow broad-spectrum antibiotic therapy
receiving it for other reasons) should be
-associated
attempt to stop or
(if the patient is
made. Oral
Diagnosis of
Infections
Anaerobic
Bacterial
Treatment of
Infections
Anaerobic
Bacterial
30% of Bacteroides
gracilis and some organisms in the B fragilis
group can be resistant to clindamycin.
Metronidazole is another potent antianaerobic drug with even
less activity against aerobes than clindamycin. It should not be
used as monotherapy if aerobes are suspected. Central nervous
system penetration is good.
obstetrical
infections)
Immunization (see Table 59-1 ) and, when appropriate,
toxin
neutralization
BOX 59-3 Prevention and Control of Anaerobic
Infections
The combination of -lactams with -lactamase inhibitors is
active against most anaerobes as well as against many aerobes.
These agents include amoxicillin-clavulanic acid (oral) the
intravenous ampicillin-sulbactam, ticarcillin-clavulanic acid, and
piperacillin-tazobactam.
The carbapenems (imipenem and meropenem) have excellent
anaerobic activity as well as broad gram-positive and gramnegative aerobic coverage. Both the -lactam and -lactamase
inhibitor combinations and the carbapenems are typically more
expensive than combination regimens using older agents.
Prevention
Preventive measures are aimed at minimizing contamination of
Immunization
59-2.
Tetanus
immunization.
REFERENCES
Aldridge KE: The occurrence, virulence and antimicrobial
resistance of anaerobes in polymicrobial infections. Am J
Surg 1995;169(Suppl 5A):2S.
Bokkenheuser V: The friendly anaerobes. CID 1993;16
(Suppl 4):S427.
Bonten M: Diagnosis and treatment of nosocomial
pneumonia. Br Jr Hosp Med 1995;57(7):335.
Connor DH et al (editors): Pathology of Infectious Diseases ,
Appleton & Lange, 1997.
Eschenbach DA: Bacterial vaginosis and anaerobes in
obstetric-gynecologic infection. Curr Inf Dis 1993;16 (Suppl
4):S282.
Finegold SM: Overview of clinically important anaerobes.
Curr Inf Dis 1995;20(Suppl 2):S205.
Finegold SM et al: Current perspectives on anaerobic
infections: Diagnostic approaches. Inf Dis Clin North Am
1993;7(2):257.
Goldstein EJC: Selected nonsurgical anaerobic infections:
Therapeutic choices and the effective armamentarium. Curr
Inf Dis 1994;18(Suppl 4):S273.
Gorbach SL: Antibiotic treatment of anaerobic infections.
Curr Inf Dis 1994;18(Suppl 4):S305.
Diseases. WB
2001
McGraw-Hill
Francisella,
Pasteurella,
Yersinia,
&
HACEK
60
Brucella, Francisella,
& HACEK
Pasteurella,
Yer
Elie F. Berbari MD
Walter R. Wilson MD
BRUCELLOSIS
Essentials
of
Diagnosis
General
chain
reaction.
Considerations
on solid media. Colonies are small, smooth, translucent, and amber color
six known Brucella species, only four are reported to cause human disea
abortus (cattle), B melitensis (goats), B suis (pigs), and B canis (dogs).
may be distinguished from each other by their requirements for carbon
atmosphere for growth, growth in the presence of dyes, production of h
sulfide and urease, and specific agglutination in antisera.
phagocytic cell where they may be killed rapidly, or the organisms may
destroy the phagocytic cell. This results in proliferation within the retic
system and the formation of noncaseating granulomas in affected tissue.
Clinical
Findings
P.631
any localization, the disease is classified as chronic. Physical examinatio
normal in most cases, may reveal bilateral diffuse lymphadenopathy, sp
and hepatomegaly in 20%30% of patients.
In the localized form, the infection may affect virtually any organ system
osteoarticular, gastrointestinal, genitourinary, and cardiovascular are am
more common affected systems. These forms have signs and symptoms
Laboratory
Findings. Patients typically have a mild anemia, neutropeni
rarely thrombocytopenia. The diagnosis of brucellosis is made with certa
Brucella spp. are recovered from cultures of the blood, bone marrow, or
Bone marrow cultures are more often positive than are blood cultures. B
cultures are often negative in chronic or localized forms. The standard B
serum agglutination test is the most widely used serologic test for the d
The current serum agglutination test does not detect antibodies directed
Brucella canis , and diagnosis requires a special serologic test or a posit
After successful therapy, the antibody titer may become negative in app
year but may remain positive in low titer throughout the patient's life. P
Polymerase chain reaction may be used for diagnosis. Primers are directe
different sites of the genomic bacterial DNA. The specificity and sensitivit
technique may provide a valuable tool for the diagnosis of brucellosis; h
test is not widely available.
More
Common
(perinephric
abscess,
epididymitis)
Monoarticular
arthralgias
Fever, chills, malaise, weight loss
1
Localized
Chronic 1
Relapsing
Brucellosis
Differential
Diagnosis
P.632
test since antigen of these microorganisms can cross-react with antigen of B
Treatment
Several antimicrobial agents are active against Brucella spp. (Box 60-2 ). C
therapy of two or more active antimicrobial agents is superior to monotherap
The optimum therapy for endocarditis is unclear. Most patients will require a
period (6 months) of combination antimicrobial therapy, and valvular replac
surgery is often necessary. Although rare, infective endocarditis represents 8
human brucellosis-related deaths.
Prognosis
First Choice
Doxycycline, 100 mg orally twice daily, PLUS rifampin, 600900 mg orally
46 weeks
Doxycycline, 2 2 mg/ kg orally twice daily, PLUS rifampin, 15 mg/kg orally d
46 weeks
Second Choice
Doxycycline, 100 mg orally twice daily for 46 weeks, PLUS streptomycin,
daily for the first 15 days4
TMP/SMX, 3 2.5 mg/kg orally of TMP component 4 times daily, PLUS rifampin
orally daily for 46 weeks
TMP/SMX, 3 2.5 mg/kg orally of TMP component 4 times daily, PLUS rifampin
orally daily for 6 mo, PLUS gentamicin, 1.52 mg/kg (IV or IM) in three d
Brucellosis
Children
Endocarditis-Meningitis-Spondylitis-Localized
Adults
Children
Prevention
&
Control
TULAREMIA
Essentials
of
Diagnosis
Prophylactic
Measures
Precautions
Standard
precautions
only
General
Considerations
Francisella
tularensis is the causative agent of tularemia (also called rabbit
deerfly fever), an infectious disease that occurs primarily in animals. It may
cause human disease, which most often manifests itself by one or more skin
regional lymphadenopathy, fever, and constitutional symptoms.
most common reservoirs are rabbits and ticks. Occasionally, the infection
through inhalation of aerosolized organisms. The organism is highly infe
laboratory
personnel.
Clinical
Findings
P.634
test, are reliable and widely available. A fourfold increase or decrease in
diagnostic of infection. A titer of 1:160 may represent recent or ac
infection. As many as 50% of cases will have positive titers by the secon
the illness. Titers may remain elevated for months to years after an acu
More
Common
Macular skin lesion that later becomes a pruritic papule, followed by ulc
eschar formation
erythematous,
fluctuant,
lymphadenopathy
pain
cough
patchy
infiltrates
lymphadenopathy
Common
Generalized
Generalized
maculopapular
adenopathy
rash
No skin lesions
Pulmonary
infiltrates
Skin
lesion
Lymphadenopathy
Lobar pneumonia
Pleural effusion
Nodular lesions or ulceration of the conjunctiva
Ulceroglandular
(7585%)
Typhoidal
(515%)
Pulmonary
(710%)
Oculoglandular
(05%)
Orop
Differential
Diagnosis
and
hematologic
malignancies.
Complications
Treatment
for all forms of tularemia (Box 60-5 ). Other antimicrobial agents such as t
and chloramphenicol have been used in patients who cannot tolerate amino
Their bacteriostatic effect against F tularensis may account for the high rela
Relapse is not caused by resistant microorganisms and may be treated with
course of the same antimicrobial regimen.
P.635
First
Choice
Choice
Adults
Children
Prognosis
Immunity after infection with F
Prevention
&
Control
prevention (Box 60-6 ). Gloves, masks, and goggles should be worn when h
potentially infected animals. A live attenuated vaccine is available for individ
risk such as veterinarians and meatpacking plant employees.
PL A GUE
Essentials
of
Diagnosis
General
Considerations
P.636
flea, Y pestis cells are phagocytized quickly by leukocytes and macropha
they replicate rapidly and produce the virulence antigens. The microorga
resistant to intracellular killing and they multiply in the regional lymph n
disseminate to the blood and other viscera causing profound toxemia. A
bleeding diathesis may occur as a result of the effect of plague toxin on
walls or as a consequence of disseminated intravascular coagulation.
Prophylactic
Measures
Precautions
Standard
precautions
only
Clinical
Findings
commonly via the airborne route and causes pneumonia. The pneumonic
highly contagious and is spread by inhalation of droplet nuclei from a pa
pneumonic plague.
Laboratory
Findings. Y pestis may be recovered from blood cultures or
an aspirate from buboes or sputum in the pneumonic form in 80100%
Gram stains of bubo aspirate or sputum demonstrate the characteristic
safety pin gram-negative microorganisms.
More
Common
(buboes)
Common
No
detectable
Bubonic
lymphadenopathy
(9095%)
Pneumonic
(5%)
Septicemic
(5%)
Differential
Diagnosis
venereum,
Complications
See Signs and Symptoms .
Treatment
Streptomycin, the drug of choice for the treatment of plague, reduces the c
rate from > 50% in untreated cases to 10% in treated cases (Box 60-8 ). F
who are allergic to or unable to tolerate streptomycin, tetracycline is a satis
alternative agent. In meningitis, the use of an antimicrobial agent with good
into the cerebrospinal fluid is essential. Chloramphenicol is administered at a
dose of 25 mg/kg followed by 15 mg/kg intravenously every 6 h for a 10-da
Prevention
&
Control
Primary
prevention. Patients with suspected pulmonic plague should be
strict respiratory isolation until the sputum culture is negative (Box 60-9
P.637
Chemoprophylaxis with tetracyclines or sulfonamides should be administe
individuals who have had close contact with patients with plague pneumo
household contacts of flea-borne plague cases.
Secondary
Prevention. For persons at high risk of exposure, two form
are available: a live attenuated and a formalin-killed plague vaccine.
First
Choice
Choice
Children
YERSINIOSIS
Essentials
of
Diagnosis
General
enhances
recovery
of
the
microorganisms.
Considerations
Y
pseudotuberculosis infection occurs rarely. The microorganism has bee
from many species of wild and domestic animals and from food,
P.638
water, and other environmental sources. The disease is thought to be ac
contact with infected animals or by ingestion of contaminated food. The
more common in Europe and typically affects children and adults during
months.
Microbiology. Y enterocolitica or Y
pseudotuberculosis are the pathogen
nonplague yersiniosis. They cause a gastrointestinal infection that may
itself by diarrhea or fever and abdominal pain that mimics acute append
microorganisms are gram-negative bipolar stained bacilli, nonlactose fer
urease positive. They are motile at 25C but not at 37C. They are iro
Prophylactic
Measures
Chemoprophylaxis should be administered as follows to individuals who have
contact with patients with plague pneumonia and for household contacts of
plague cases:
Tetracycline, 7.5 mg/kg orally 4 times daily for 7 days (should not be us
children under the age of 8 or in pregnant women after 6 months of ges
Sulfonamides, 7.515 mg/kg orally 4 times daily for 7 days
Isolation
Precautions
Clinical
Findings
More
Common
Enteritis: abdominal
Mesenteric adenitis
Pseudoappendicitis
pain,
diarrhea
syndrome
Septicemia
Pharyngitis
Hepatic
involvement
Skin manifestations
Lymphadenopathy
syndrome
Polyarthritis: knees, ankles, wrist, fingers, toes
Erythema nodosum
Less
Common
megacolon
Transfusion-related
Endocarditis
sepsis
Uveitis
Glomerulonephritis
Guillain-Barr
syndrome
Hemolytic uremic syndrome
Intestinal
Extraintestinal
Postinfective
First
Choice
Choice
Children
Typically, patients present with fever, abdominal pain, and diarrhea that
occasionally bloody for a 1- to 3-week duration. A clinical syndrome
indistinguishable from acute appendicitis may occur in older children and
adolescents. On laparotomy, thickening of the terminal ileum and cecal w
Differential
Diagnosis
rheumatoid
arthritis,
Kawasaki
disease,
and
other
postinfectious
ar
Complications
See Signs and Symptoms .
Treatment
(Box 60-11 ). The optimal therapy is unclear. Yersinia spp. are susceptible in
gentamicin,
fluoroquinolones,
trimethoprim-sulfamethoxazole,
third-generat
cephalosporins, tetracycline, and chloramphenicol. Empirical therapy with an
aminoglycoside alone or in combination with trimethoprim-sulfamethoxazole,
generation cephalosporin, or chloramphenicol is recommended.
Prognosis
Prevention
&
Control
PASTEURELLA
Essentials
of
Diagnosis
General
Considerations
Pasteurella
Measures
Precautions
Hospitalized
isolation
patients
Common
fever
Pharyngitis
Pneumonia
Less
Common
Abscess
Tenosynovitis
Arthritis
Sinusitis
Otitis
Mastoiditis
Empyema
Soft
Tissue/Bone
Respiratory
System
Epidemiology. Pasteurella
multocida has been recovered from cultures
specimens from the nasopharynx and the gastrointestinal tract of a large
asymptomatic wild and domestic animals. The highest carriage rates occu
(50%90%), dogs or swine (50%), and rats (15%). Infections are usu
preceded by a cat or dog bite or scratch on an extremity. Occasionally,
may occur without a bite or scratch in persons who have frequent contac
animals. Fifteen percent of cases have no history of animal exposure.
First Choice
Amoxicillinclavulanic acid, 250500 mg orally three times daily for 10
Amoxicillinclavulanic acid 13.3 mg/kg orally three times daily for 10 days
-Lactam Allergy
Ciprofloxacin, 500750 mg orally twice daily
TMP/SMX, 46 mg/kg TMP orally twice daily
Adults
Children
Clinical
Findings
Signs and Symptoms. Hours to days after direct contact with an anima
way of a dog or cat bite), a soft tissue infection develops (Box 60-13 ).
complain of an acute onset of pain, erythema, and swelling at the site o
usually on the hand, leg, arm, or head and neck. Serosanguineous drain
Laboratory
Findings. Gram-negative bipolar bacilli appear on Gram sta
drainage. Cultures of the organism confirm the diagnosis.
Differential
Diagnosis
After an animal bite, the differential diagnosis should include infection cause
anaerobes, staphylococci, streptococci, tularemia, and cat-scratch disease.
Complications
P.641
Occasionally, pharyngitis occurs in patients with close contact with infected
especially cats. Rarely, P multocida may cause meningitis, sinusitis, pharyng
otitis, empyema, peritonitis, pyelonephritis, surgical wound
Associated bacteremia can occur with any organ infection.
Prophylactic
infection,
and
Measures
Treatment
Prevention
&
Control
Avoidance of contact with wild or domestic animals is probably the only mea
preventing human P multocida infections (Box 60-15 ).
More
Common
Fever
Periodontal disease
New or changing cardiac murmur
Splenomegaly
Embolic phenomena
Brain abscess: fever, confusion, focal findings
Meningitis
Arthritis: swelling, pain, and effusion of the affected joint
Less
Common
Other
Sites
Infective
HACEK
INFECTION
Essentials
of
Diagnosis
General
Considerations
infection
(E
corrodens ).
chocolate agar) and increased CO2 tension. Cultures often require prolo
incubation times (average 57 days) for growth. They are
P.642
distinguished among each other by their biochemical reactions.
First
Choice
Choice
Children
Clinical
Findings
a prosthetic heart valve was present in 60% and 27% of cases, respecti
valvular vegetation observed by echocardiography is characteristically la
finding probably reflects the chronicity of infection before diagnosis. Sign
symptoms of other HACEK infections are related to the affected site of
Laboratory
Findings. The diagnosis of HACEK infections requires the c
the bacteria from sterile sites. Biological specimens need to be incubated
media under increased CO2 tension for 57 days.
Differential
Diagnosis
Treatment
Prognosis
Native or prosthetic valve endocarditis caused by HACEK organisms may be
Prevention
&
Control
REFERENCES
Brucellosis
Tularemia
Jacobs RF: Tularemia. Adv Ped Infect Dis 1996;12:55.
Stewart SJ: Tularemia: association with hunting and farming. FEMS Immun
Microbiol 1996;13: 197.
Plague
&
Yersiniosis
1997;10:35.
Agents
Pasteurella
Chemother
1995;39:2153.
Infection
Goldstein EJ: Bite wounds and infection. Clin Infect Dis 1992;14:633.
HACEK
Infection
2001
McGraw-Hill
61
Tuberculosis
Julie Brahmer MD
Merle A. Sande MD
Essentials
of
Diagnosis
institutionalized
patients,
and
HIV-positive
General
Considerations
Mycobacterium
tuberculosis is still an important pathogen.
Approximately one-third of the world's population is infected
with M tuberculosis , according to World Health Organization
estimates, resulting in 2.9 million annual deaths. In the United
States, tuberculosis is on the rise, after several decades of
steady decline.
The disease develops in a subset of those who are infected. In
most patients, the reason disease develops is unclear unless
they are immunosuppressed by either HIV infection or other
immunocompromising diseases. HIV has played a major role in
the resurgence of tuberculosis in the United States and in the
emergence of multidrug-resistant disease. Prompt diagnosis and
treatment of active disease is important in all patients to
prevent severe disease and infection of the surrounding
population. In those infected with the tuberculosis bacillus, the
prevention of active tuberculosis disease is also important.
Epidemiology. In the United States, tuberculosis had been
on the decline until 1985, when the number of cases began
to increase. This increase was undoubtedly a result of the
HIV epidemic. Cases continued to increase until 1995, when
the 22,813 new cases documented in the United States
constituted a 6.4% drop from 1994. This drop resulted from
a decreased incidence in the U.S.-born population. The
overall incidence of tuberculosis in the United States is quite
low, but case rates are high among specific groups such as
HIV-infected patients, the homeless, recent immigrants from
countries that have a high prevalence of tuberculosis,
intravenous drug users, inner-city dwellers, and minorities.
In the late 1980s, tuberculosis caused by organisms
resistant to antimicrobial agents increased sharply,
especially in New York City, where, in 1991, one-third of all
cases were resistant to at least one agent. The rates of
resistance in the United States began to decrease in 1995.
Of cases reported, the isoniazid (INH) resistance rate was
7.6%, and the INH-rifampin resistance rate was 1.4%. The
P.645
Pathogenesis. A person is infected with M tuberculosis by
inhaling bacilli in droplet nuclei. The particles must be
retained in the lung. Thus the inhaled particles, which are <
5 m in size, travel to the alveolus during inspiration and
are retained in the lung. Larger particles are filtered out
before they reach the alveoli. In the alveolus, the bacillus
activates the immune system. The first line of defense is the
alveolar macrophage. These macrophages engulf the bacilli.
Some macrophages are capable of killing the bacillus,
whereas others cannot. The bacilli multiply within the cells.
The factors controlling the macrophages' ability to kill M
tuberculosis are
rate, T cells are
recognize the M
macrophage. The
tuberculosis.
Active tuberculosis disease is defined as tissue involvement
by the M tuberculosis bacillus that progresses to produce
clinical symptoms and signs. On average, illness develops in
35% of infected patients. Of the other 9597% of
infected patients, 5% develop active tuberculosis in their
lifetime. M tuberculosis infection can cause several clinical
syndromes.
More
Common
Lymphatic
Other extrapulmonary
sites
Pulmonary
Less
Common
Pulmonary
Extrapulmonary
Children
Adults
CLINICAL
tuberculosis
SYNDROMES
PULMONARY
TUBERCULOSIS
Clinical
Findings
EXTRAPULMONARY
TUBERCULOSIS
TUBERCULOSIS IN
HIV INFECTION
PATIENTS
WITH
Diagnosis
Diagnoses of extrapulmonary and pulmonary TB are the same. A
skin test (PPD) is used to prove infection: 0.1 mL of PPD is
placed intradermally on the volar surface of the forearm by
means of a 26-gauge needle. At 4872 h after injection, the
diameter of induration, not erythema, is measured. A positive
skin test reaction is caused by a delayed-type hypersensitivity
response, which is directed at the TB protein antigens. Other
tests include demonstration of the bacillus by means of culture
or AFB smear of affected organs or blood culture in
disseminated
disease.
Interpreting Tuberculin Skin Tests. The criteria vary for
interpreting a PPD test as positive. An induration 5
errors
Improper
administration
Inaccurate reading
Loss of potency of antigen
Patient-related
factors
Age
Nutritional status
Medicationscorticosteroids,
immunosuppressives,
anti-neoplastic
agents
Severe
tuberculosis
Coexisting diseases such as renal failure
HIV infection
Viral illness or vaccination
Lymphoreticular
malignancies
Sarcoidosis
Solid tumors
Lepromatous
leprosy
Sjgren's
syndrome
Ataxia
telangiectasia
Uremia
Primary biliary cirrhosis
Systemic lupus erythematosus
Severe systemic disease of any etiology
1
More
Common
Disseminated
Pulmonary
Pulmonary
Disseminated
Less
Common
Other
extrapulmonary
sites
Other
extrapulmonary
sites
Children
Adults
Treatment
Treatments of active extrapulmonary and pulmonary TB are the
same. Treatment should be started presumptively before
diagnosis in patients with severe disease thought to be TB.
Treatment usually does not reduce the isolation rate of AFB in
the first several days. In patients with less severe disease or
those who present diagnostic dilemmas, therapy can be withheld
until a diagnosis is made or until several specimens have been
collected.
Patients should be started initially on a four-drug regimen until
drug susceptibility tests are finalized, unless the patient is from
an area where drug resistance is very low. Most communities in
the United States have a > 4% incidence of cases resistant to at
least one drug. However, if a community has a < 4% resistance
rate, an initial three-drug regimen is acceptable.
Choice of Treatment Regimen. There are several
available regimens for treatment (Box 61-3 ). Several
considerations should be made when deciding on a
particular regimen. These include the probability of primary
resistance, previous treatment for tuberculosis, patient
compliance, other coexisting illnesses, drug susceptibility of
the organism, and history of hypersensitivity to or side
effects of antituberculosis drugs. The risk factors for drug
resistance include > 4% of INH resistance in the
community, prior treatment with INH, exposure to a known
drug-resistant case, immigration from countries with a high
incidence of drug resistance (countries in Asia, Africa, or
Central or South America), HIV coinfection, and intravenous
drug use. These patients should be placed on an initial four-
tuberculosis bacillus.
DC,
discontinue.
First
Option
Second
Option
Third
Option
neuritis
(prevent
by
co-administering
Pyrazinamide
Arthralgia
Hyperuricemia
None noted by the PDR
Rifampin
Elevated liver function tests
Flulike syndrome
Discoloration of secretions which stain
Induces cytochrome P-450 system
Inhibits effects of oral contraceptives, quinidine,
corticosteroids, warfarin, methadone, digoxin, and
oral
hypoglycemics
Streptomycin
Ototoxicity
Potentiates the action of neuromuscular blocking agents
1
Major Side
Effects
Major Drug
Interactions
HIV-negative
injection
drug
users
illness
or
therapy
(diabetic,
renal
from
high-prevalence
countries
identified
high-prevalence
groups
(migrant
persons
15 mm increase if 35 years old
All persons
PPD negative but high risk
Anergic
All
persons
HIV-infected
persons
Reaction
Classification
Table
First-Line
Persons
Recommended
Preventive
for
Therapy
Drugs
Isoniazid
Daily dose 1015 mg/kg/d (300 mg/d max)
2weekly dose 2040 mg/kg/ dose (900 mg/dose
max)
Rifampin
Daily dose and 2weekly 1020 mg/kg/d (600 mg/d
per dose max)
Pyrazinamide
Daily dose 1530 mg/kg/d
2weekly 5070 mg/kg/dose
Max dose 2 g
Streptomycin
Daily dose 2040 mg/kg/d IM (max dose 1 g)
2weekly dose 2530 mg/kg/ dose IM
Ethambutol
Daily dose 1525 mg/kg/d
2weekly dose 50 mg/kg/ dose
Max dose 2.5 g
Ethambutol
(bacteriostatic)
Daily dose 25 mg/kg/d for 2 mo, then 15 mg/kg/d
2weekly dose 50 mg/kg/dose
Isoniazid
(bactericidal)
Daily dose 510 mg/kg/d (300 mg/d max)
Drugs
Ethionamide
1020 mg/kg/d (max dose 1 g)
Kanamycin
Daily dose 15 mg/kg/d IM
2weekly dose 1525 mg/kg/ dose IM or IV
Max dose 1 g
Cycloserine
Daily dose 1020 mg/kg/d (max dose 1 g)
Amikacin
(bactericidal)
7.510 mg/kg IVor IM daily
Capreomycin
sulfate
1 g/d (15 mg/kg/d) IM
Ciprofloxacin
750 mg orallyor IV twice a day
Clofazimine
50 mg/d + 300 mg 1/mo supervised or 100 mg/d
orally
Cycloserine
(bacteriostatic)
7501000 mg/d (15 mg/kg/d) in 24 doses/d orally
Ethionamide
(bacteriostatic)
5001000 mg/d (1015 mg/kg/d) orallyin 13
doses/d
Ofloxacin
400 mg orally or IV twice a day
Para-aminosalicylic
acid
(bacteriostatic)
46 g orally twice a day (200 mg/kg/d)
Rifabutin
300 mg/d orally
Special
Considerations
Adults
of
Mycobacterium TB
Prophylactic Measures
Preventative therapy for PPD-positive patients and known
household contacts
See Table 61-5 for preventative therapy
Isolation
Precautions
Prevention
&
Control
is critical. Isolation
alone, or in a
should have
air per hour with
also
Any
a
be
(see
below).
Organisms
Prevention
Therapy
First
Option
61-5.
Among
Other
Options
Health
Care
Workers
Health care workers should have regular PPD checks unless they
have a history of PPD positivity. Most centers recommend yearly
PPDs. PPDs should be placed on anyone who is a household
contact of a patient with active TB or anyone who has had close
If a person has a high risk of exposure to INH- or rifampinresistant organisms, the data for the efficacy of preventative
therapy are limited. If the risk of infection with INH-resistant
organisms is high and the patient would be unable to tolerate
the disease, rifampin should be used. If the patient was exposed
to INH- and rifampin-resistant organisms, a multidrug
preventive therapy should be used. Each case must be assessed
individually (Table 61-5 ).
BCG vaccination
the ability of a
Mycobacterium
effectiveness of
use are limited.
REFERENCES
American College of Physicians: Medical Knowledge Self
Assessment Plan 11, 1997.
Arky R: Physicians
Desk
1997.
Barnes PF: Rapid diagnostic tests for tuberculosis. Am J Resp
Crit Care Med 1997;155:1497.
Brahmer JR, Small PM: Tuberculosis and nontuberculous
mycobacterial infections. In Stein JH: Textbook of Internal
Medicine , 5th ed. Mosby Yearbook, 1998.
Department of Health and Human Services: Tuberculosis
morbidityUnited States, 1994. Morbid Mortal Weekly Rep
1995;44:387.
Hopewell PC: Tuberculosis in persons with human
immunodeficiency virus infection. In MA Sande, PA
Volberding: The Medical Management of AIDS , 5th ed.
Saunders, 1997.
Long SS (editor): Mycobacterium
tuberculosis. In Principles
and Practice of Pediatric Infectious Diseases , Churchill
2001
McGraw-Hill
Mycobacteria
62
Other
Mycobacteria
Julie Brahmer MD
Yenjean Hwang MD
Merle A. Sande MD
Essentials
of
Diagnosis
General
Considerations
CLINICAL
SYNDROMES
MYCOBACTERIUM
AVIUM COMPLEX
(DISSEMINATED & PULMONARY
DISEASE)
M avium is the most common atypical mycobacterium to cause
disease in humans. In immunocompetent patients, M avium can
cause pulmonary disease (Box 62-1). It is the most common
pulmonary pathogen of
several risk factors for
Patients with underlying
gastrectomy, and those
Table
Mycobacterium
species
Tuberculosis
Habitat
Common Diseases in
Humans
Humans
Bronchopulmonary
Humans,
cattle
complex
M
tuberculosis
M bovis
Photochromogens
kansasii
Water,
cattle
Skeletal
marinum
Fish,
water
M simiae
Primates
Bronchopulmonary
Primates
Pulmonary
Soil,
water,
foodstuffs
Lymphadenitis
Unknown
Bronchopulmonary
asiaticum
(rare)
Scotochromogens
M
scrofulaceum
szulgai
gordonae
Water
Pulmonary
(rare)
flavescens
Soil,
Pulmonary
(rare)
xenopi
Water
Bronchopulmonary
Soil,
water,
Pulmonary,
lymphadenitis,
swine,
cattle,
birds
disseminated
Unknown
water
Nonchromogens
M aviumintracellulare
ulcerans
tissue
gastri
Soil,
water
Pulmonary
(rare)
terrae
Soil,
water
Pulmonary
(rare)
Rapid
growers
fortuitum
Soil,
water,
animals,
marine life
abscessus
Soil,
water,
animals,
marine life
chelonae
Soil,
water,
animals,
marine life
smegmatis
Moist
surfaces,
urogenital
Pulmonary
(rare)
flora
M leprae
1 Adapted
Pediatric
Humans,
ninebranded
armadillos
including skeletal
nodules, fascitis,
cause superficial
ulcers, abscesses, or
Clinical
Findings
Children
Adults
More
Superficial
Colonization
Common
lymphadenitis
Cutaneous
ulcers,
abscesses
and plaques
Pulmonary
infectionproductive
cough hemoptysis in
<25%, fever and
weight loss in 33%
Less
Common
Pulmonary
Disseminated
disease
Cutaneous lesions
Lymphadenitis
Disseminated
disease
Children
More
Common
Adults
Disseminated
disease
Pulmonary
disease
Colonizationgastrointestinal
and
respiratory tracts
Fever, drenching
night sweats, weight
loss, diarrhea,
abdominal pain,
anorexia,
hepatosplenomegaly,
adenopathy,
anemia
Less
Common
and
Isolated
lymphadenitis
Pulmonary infection
Osteomyelitis,
Isolated
cutaneous
lesions
peritonitis, oral
lesions,
appendicitis
MYCOBACTERIUM
LEPRAE
(LEPROSY)
cases of leprosy except those that are imported from areas where
leprosy is endemic. Risk factors for acquisition of leprosy in
endemic areas include poverty and rural residence. However, even
in endemic areas, the distribution of leprosy can vary greatly,
sometimes with significant differences in incidence of leprosy in
adjacent villages. In North America, armadillo contact has been
reported as a risk factor for acquisition. Other risk factors that
have been reported in certain populations are the human leukocyte
antigens HLA-DR3 (with the tuberculoid or paucibacillary form of
disease) and HLA-MTI (with the lepromatous or multibacillary form
of disease). Interestingly, the proportions of the lepromatous and
tuberculoid types of leprosy (Box 62-3) vary geographically; in
Mexico, 90% are lepromatous, whereas, in India and Africa, 90%
are tuberculoid.
Table
avium
1 For
Clinical
Findings
are
from
no
high
P.656
symmetric and generalized. There is a characteristic deformity
associated with this type of leprosy, saddle-nose
deformity, which occurs because of infiltration of the upper
respiratory system and nasal cartilage. Other upper respiratory
system effects include chronic nasal congestion and epistaxis.
The tuberculoid, or paucibacillary, form of leprosy is
characterized by one or few hypopigmented macules, which are
Table
leprae
leprae Syndromes
Lepromatous
Forms
Tuberculoid
Forms
Symmetrical skin
plaques, nodules, or
thickened dermis,
Few hypopigmented
anesthetic macules with
distinct elevated and
erythematous
borders
Large and asymmetric
peripheral nerve
involvement
generalized
peripheral
neuropathy
Diffuse
lepromatosis
seen in Mexican
patients, diffuse
dermal infiltration
without focal lesions
Normal-looking
skin
MYCOBACTERIUM
KANSASII
PULMONARY
INFECTION)
(CHRONIC
Clinical
Findings
pulmonary
infection
that
resembles
pulmonary
tuberculosis.
Findings.
Nonspecific.
MYCOBACTERIUM
SCROFULACEUM
(LYMPHADENITIS)
M scrofulaceum is a ubiquitous scotochromogenic mycobacterium
that commonly exists in soil and water and contaminates reagents
and foodstuffs. It readily colonizes respiratory secretions of healthy
children and adults. The most common clinically evident disease in
humans is lymphadenitis, which is commonly seen in children < 12
years old.
Clinical
Findings
Findings.
Nonspecific.
MYCOBACTERIUM
BOVIS
(TUBERCULOSIS IN ANIMALS)
M bovis is considered to be part of the M tuberculosis complex. It is
a nonchromogen and generally takes 2140 days to isolate in
culture. Its natural reservoir is humans and cattle, and it generally
causes tuberculosis in cattle, goats, cats, dogs, primates, and other
wildlife. It is rarely a cause of tuberculosis in humans, although
there are reports of it causing 3% of the tuberculosis cases in
certain places such as San Diego, California. An attenuated strain
of M bovis is used for bacille Calmette-Gurin (BCG) vaccine.
Transmission of the organism occurs by inhalation of aerosol or by
direct inoculation. Transmission by ingestion of contaminated milk
from infected cows did occur prior to routine pasteurization.
Clinical syndromes associated with M bovis include soft tissue
infection. Soft tissue infection has been reported after accidental
Clinical
Findings
Findings.
Nonspecific.
MYCOBACTERIUM
MARINUM
FISH TANK GRANULOMA)
(CLASSIC
Clinical
Findings
Diagnosis
The diagnosis of atypical mycobacterial infections
P.658
may be difficult to make with certainty. It is often unclear whether
the presence of an atypical mycobacterium in a clinical specimen
indicates infection or colonization. The diagnosis of an infection
with mycobacteria should be made only in the presence of an
illness associated with mycobacteria and when other causes of
disease have been excluded. Another clue that helps distinguish
colonization from infection is the quantity of growth in culture.
Heavy growth of one organism in culture is more suggestive of
infection than of colonization; light growth is suggestive of
colonization, unless the organism was isolated from a normally
sterile body fluid. It is often helpful to notify the microbiology
laboratory when infection with an atypical mycobacterium is
suspected, because the nontuberculous mycobacteria often have
very specialized culture requirements.
Experience is needed for accurate interpretation of the appearance
of mycobacteria in stained specimens. Typically, fluorochrome,
Kinyoun, and Ziehl-Neelsen stains are used. Cultures are incubated
at 37C in 10% carbon dioxide and 90% air, usually for
68 weeks. (More detailed information regarding laboratory
diagnosis can be found in a standard microbiology text.) Typically,
detection of growth in culture can be made within 2 weeks, but
identification and speciation may take 24 weeks.
Susceptibility testing has not been standardized, and all significant
isolates need to be tested for antibiotic susceptibility. However,
susceptibility to an antibiotic in vitro has not been directly
correlated to clinical efficacy.
Diagnosis of MAC, M bovis, and M marinum infections is determined
by acid-fast bacillus smear and culturing from the infected tissue.
Diagnosis of M scrofulaceum infection is made by identification of
granulomatous inflammation in skin biopsy and isolation of the
organism from culture. Diagnosis of M kansasii infection is difficult,
especially since there can be a concurrent infection with M
tuberculosis.
Diagnosis of leprosy depends on clinical information as well as
biopsy of affected dermis; viable organisms stain brightly and
uniformly (see Table 62-3). Nonviable organisms stain in an
irregular manner. A skin biopsy taken from a patient with
suspected leprosy should be stained with hematoxylin and eosin, as
well as with Fite stain for acid fastness.
The two polar forms of leprosy are the lepromatous, or
multibacillary, and the tuberculoid, or paucibacillary (see Box 62-3
for features of both). Most patients will have intermediate forms.
In lepromatous patients, skin biopsies should be taken at sites of
skin lesions, but normal looking skin will also have pathologic
changes. Lesions will show many bacilli in clumps and foam cells
loaded with bacilli in the dermis. Granulomatous changes may be
seen in the liver, spleen, and lymph nodes. In tuberculoid patients,
biopsies should be done only at sites of lesions because biopsies of
normal appearing skin will be nondiagnostic. Skin biopsies from
tuberculoid patients will show few or no organisms but will show
granulomas of epithelial cells, lymphocytes, and foreign-body giant
cells near dermal appendages, especially dermal nerves. The
pathognomic lesion for tuberculoid leprosy is acute granulomatous
invasion and destruction of dermal nerves. Most patients, however,
have intermediate, or borderline, forms of leprosy, and their
biopsies will show a mixture of findings.
An intradermal skin test is available that uses heat-killed M leprae.
However, use of the skin test to make the diagnosis of leprosy is
unreliable. Although the skin test will be positive in tuberculoid
patients, treated lepromatous patients and unaffected individuals in
endemic areas will show positive results as well. Lepromatous
patients will be anergic specifically to M leprae but will have a
normal response to intradermal recall antigens, such as purified
protein derivative. Various M leprae lipid and carbohydrate
constituents are believed to impair macrophage and T-lymphocyte
function specifically against M leprae. There also seems to be an
increase in the number of T-suppressor cells. Cytokines such as
interleukin 2 (IL-2), interferon (IFN-), IL-4, IL-5, and IL-10
Treatment of
Infections
Atypical
Mycobacterial
First
Choice
Adults
Children
Clarithromycin 500 mg
PO twice daily +
ethambutol 1525
mg/kg PO + rifabutin
Clarithromycin, 7.5
mg/kg PO twice daily
(max. dose 500
mg/dose) in children
Second
Rifampin + ethambutol
Choice
+ clofazamine +
ciprofloxacin, 750
PO twice daily
mg
First
Choice
Second
Choice
Clarithromycin or azithromycin +
ethambutol + rifabutin + 1 or more of
the
following
Ciprofloxacin, 750 mg PO twice
daily
Ofloxacin, 400 mg PO twice daily
Amikacin, (7.515 mg/kg) IV or
IM
Pediatric
Considerations
Prophylactic
Measures
Isolation
Precautions
None
Adults
First Choice:
Tuberculoid
Dapsone, 100 mg
once daily
unsupervised +
rifampin, 600 mg
leprae
Children
Correspondingly
lower dose
First Choice:
Lepromatous
Dapsone, 100 mg
once daily +
clofazamine, 50 mg
once daily
unsupervised O R
rifampin, 600 mg
once daily +
clofazamine, 300 mg
every month
supervised for 24
months
Alternative
Choice
Ethionamide, 250 mg
once daily or
prothionamide, 375
mg once daily in
place of clofazamine;
minocycline,
clarithromycin, or
fluoroquinolone
reportedly
bactericidal
Correspondingly
lower doses
REFERENCES
Adal KA, Wispelwey B: Mycobacterium
avium complex peritonitis
in a patient with alcoholic liver disease. J Clin Gastroenterol
1996;22(3):245.
Atiyeh BS et al: Bacille Calmette-Gurin (BCG)-itis of the
hand: a potential health hazard for health workers. Ann Plast
Surg
1996;36(3):325.
Baron E, Peterson L, Finegold S: Mycobacteria, p 590. In Baron
Microbiology, CV
avium
Clin
Infect
Dis
1995;21(5):1325.
infection
marinum. J
1995;22(8):1607.
avium complex
2001
McGraw-Hill
63
Actinomycetes
Phyllis C. Tien SM MD
David A. Relman MD
Actinomycetes are variably acid-fast, gram-positive bacilli that
are sometimes filamentous and branched. Originally thought to
be fungi due to their hyphae-like appearance, they are now
recognized as bacteria based on their cell wall components,
reproduction by fission without sporulation or budding,
inhibition by antibacterial agents, and molecular phylogenetic
analysis. The actinomycete chromosomes contain a high content
of guanosine and cytosine. The actinomycetes include the
genera Mycobacterium and Corynebacterium, which are
discussed in Chapter 61 and Chapter 62, respectively. The
actinomycetes also include the genera Nocardia,
Actinomyces,
Rhodococcus, Tsukumurella, Gordona, Actinomadura, and
Streptomyces, as well as the Whipple's disease bacillus
Tropheryma
whippelii. Of these, members of the genus Nocardia
are the most significant from a clinical standpoint, followed by
organisms from the genus Actinomyces. The other
actinomycetes discussed in this chapter are less common causes
of disease in humans.
NOCARDIA
Essentials
of
Diagnosis
Gram-positive, variably
aerial hyphae.
acid-fast,
branching
filaments
with
General
Considerations
Clinical
without cavitation, a
or pneumonia with
disease ranges from
wax and wane.
cutaneous
disease.
Nocardiosis
Diagnosis
A Gram stain that shows thin, delicate, variably gram-positive,
irregularly stained or beaded branching filaments is suggestive
of nocardiosis. The diagnosis must be confirmed by culture.
Currently, there is no reliable serodiagnostic test.
This normally elusive organism can usually be detected in pus or
abscess drainage from a fistula, which should be submitted in a
sterile tube or syringe. Fibers from sterile cotton swabs can
interfere with the interpretation of smears, so the use of swabs
should be discouraged. Surgical tissues and biopsy material
from lung, skin, or brain should be kept moist during transport.
When examining sputum specimens, early-morning expectorated
samples should be collected on 3 separate days. Single smears
and cultures are positive in only one-third of cases, so multiple
specimens are encouraged.
Nocardia spp. grow readily on most of the media used for
bacterial, fungal, and mycobacterial growth. Their growth can
be enhanced if they are incubated at between 32 and 35C in
the presence of 510% carbon dioxide. They are slow
growing, so the laboratory should be alerted when Nocardia
infection is suspected. Colonies from pure cultures form within
4872 h, but, with complex specimens such as respiratory
(PCR-RFLP)
Differential
analysis.
Diagnosis
Treatment
Sulfonamides have been the mainstay of therapy for Nocardia
infections since the first report of a cure in 1944. Prior to the
1940s, infections with Nocardia spp. were almost always fatal.
Today the combination of trimethoprim and sulfamethoxazole
(TMP-SMX) is generally the drug of choice despite inadequate in
vitro data regarding synergy with this drug combination (Box
63-2). Between 90 and 95% of pulmonary infections with
First
Choice
Second
Choice
1 CNS
receive
Prevention
continuous
&
suppressive
therapy.
Control
ACTINOMYCES
Essentials
of
Diagnosis
branching
under
with
the
filaments
arranged
in
ray-like
microscope
characteristic
molar
tooth
appearance
General
Considerations
earlier
introductory
comments.
tracts
is often
enlarge,
discharging
Clinical
aspiration,
bronchoscopic
More
Common
Cervicofacial,
especially
perimandibular region (~50% of
cases)
Draining sinus fistulas common
Less
Common
Thoracic (~15%)
Abdominal disease (~20%)
Pelvic disease associated with
intrauterine device use
Diagnosis
Sulfur granules are hard, irregularly shaped yellow
particles that range in size from 0.1 to 5 mm. Microscopically,
they appear as masses of bacterial filaments that may be
arranged in ray-like projections. Their presence is typical, but
not unique to this disease. Other organisms such as Nocardia
spp., Streptomyces spp., and staphylococci in botryomycosis
may form similar granules. A definitive diagnosis is made by
growing the organism from an appropriate specimen in
anaerobic culture media.
Timely procurement of specimens before initiation of
antimicrobial therapy and submission to the laboratory using
anaerobic transport kits optimize recovery of the organism by
culture. Tissue, pus, or sulfur granules are the specimens of
choice, and swabs should be avoided because the cotton
filaments may be confused on microscopy with the organism.
Multiple
P.667
specimens should be obtained because organisms may be scarce
in pathology specimens.
Growth usually appears within 57 days but can take as long
as 24 weeks, so the lab should be alerted if actinomycosis is
suspected. Growth plate media containing 5% sheep blood or
rabbit blood supplemented with hemin and vitamin K should be
used. However, other types of media including anaerobic blood
culture medium, enriched thioglycolate medium, and chopped
meat-glucose medium will support the growth of these
organisms. Plates should be incubated at 35 to 37C in an
anaerobic chamber. Often colonies are viewed first as
spiderlike in appearance and mature to resemble a
molar tooth. Biochemical tests are performed to
distinguish the various species. There are no specific antibody
or antigen detection tests.
Differential
Diagnosis
Treatment
Penicillin is the drug of choice for actinomycosis (Box 63-4) .
Prolonged therapy is necessary to achieve a cure and minimize
relapse. Intravenous penicillin G for 26 weeks followed by
oral penicillin for 612 months is a reasonable regimen.
Treatment should extend beyond the resolution of measurable
disease. Long-term therapy is necessary because of the amount
of reactive fibrosis formed by infection. Relapse is common
especially after a short course of empiric antibiotic therapy. For
patients with penicillin allergies, tetracycline is the preferred
agent. Minocycline erythromycin and clindamycin are also
reasonable alternatives. In vitro susceptibility data suggest that
oxacillin, dicloxacillin, cephalexin, metronidazole,
aminoglycosides should be avoided.
and
the
First
Choice
Second
Choice/PenicillinAllergic
Prevention
&
Tetracycline,
minocycline,
erythromycin, or clindamycin
(standard doses not available)
Control
OTHER
ACTINOMYCETES
Three
species, S
somaliensis,
Streptomyces
P.668
and Streptomyces
anulatus, have been implicated in human
disease, primarily in the formation of actinomycetomas. S
somaliensis and S paraguayensis are rarely, if ever, found in the
United States. They primarily inhabit Latin America, although S
somaliensis is also known to cause disease in the arid regions of
Africa and Arabia. S anulatus, on the other hand, has been
associated with lung disease and sepsis, brain abscess, and
panniculitis, as well as cervical lymphadenitis in an
immunocompromised patient in the United States. Isolation of
the streptomycetes should follow procedures used for the
REFERENCES
Nocardia
Beaman B, Beaman L: Nocardia
species:
relationship.
1994;7:213.
Clin
Microbiol
Rev
host-parasite
and
actinomycetoma.
Actinomyces
Fiorino AS: Intrauterine contraceptive device-associated
actinomycotic abscess and Actinomyces detection on cervical
smear. Obstet Gynecol 1996;87:142.
Smego RA Jr, Foglia G: Actinomycosis. Clin Infect Dis
1998;26:1255.
Other
and
actinomycetoma.
Actinomycetes
2001
McGraw-Hill
pallidum
64
Treponema
pallidum
Fred A. Lopez MD
David A. Relman MD
Essentials
of
Diagnosis
General
Considerations
The term syphilis was first used in 1530 by the Italian physician
Girolamo Fracastoro in his epic poem Syphilis Sive Morbus
Gallicus. Much has been learned since then about this sexually
transmitted disease caused by T pallidum. Public health
screening programs and the introduction of antibiotics led to a
marked decline in the number of new cases of syphilis in the
United States after World War II. However, the advent of AIDS
was associated with an increase in new cases of syphilis,
necessitating the reeducation of health care personnel in the
evaluation and management of this disease.
Epidemiology. Genital herpes and syphilis are the most
common causes of genital ulcerations in patients presenting
to sexually transmitted disease clinics in the United States.
Syphilis is usually transmitted by sexual contact with the
infectious lesions of primary and secondary syphilis. Syphilis
develops in ~ 3060% of sexual contacts of individuals
with infectious syphilis. Syphilis is less commonly
transmitted in utero or by means of blood transfusion,
nongenital body contact, and accidental direct inoculation.
The incidence of primary and secondary syphilis (called
early syphilis) reached a nadir in 1956 and then increased
slowly. Two epidemics of early syphilis in the past
20 years have highlighted the role of human behavior in
syphilis epidemiology: one peaked in 1982 and primarily
involved bisexual and homosexual men; the second peaked
in 1990 when 50,223 new cases of primary and secondary
syphilis were reported. This epidemic was associated with
crack cocaine use and its effects on sexual behavior and
disproportionately involved African Americans. The incidence
of this outbreak was highest in the southern United States
PRIMARY
Clinical
SYPHILIS
Findings
and
P.671
P.672
Laboratory
Findings. Definitive diagnosis can be made by
visualization of spirochetes in exudates from these lesions
with darkfield or immunofluorescent antibody microscopy.
Nontreponemal serologic testing is reactive in 7080% of
patients with primary syphilis but is less sensitive at the
time that the chancre first appears. Treponemal antibody
tests, specifically the fluorescent treponemal antibody test,
are more sensitive during this stage of infection.
Differential
Diagnosis. Primary syphilitic genital lesions
can be mistaken for lesions associated with trauma, herpes
simplex virus, malignancy, chancroid, lichen planus,
granuloma inguinale, or lymphogranuloma inguinale.
Darkfield examination is helpful in diagnosis. The painful
vesicular lesions of herpes are distinguished by
multinucleated giant cells when unroofed and examined with
a microscope. The ulcerated and nonindurated lesions of
chancroid are associated with painful lymphadenopathy.
Lymphogranuloma venereum and granuloma inguinale
infections are seen primarily in tropical countries.
More
Common
by
definition
aneurysm,
coronary
ostial
stenosis
Asymptomatic
Meningovascular
(strokelike
syndrome)
General paresis: neuropsychiatric abnormalities of dementia
Tabes dorsalis: ataxia, areflexia, lower extremity pain,
incontinence, impaired proprioception
Less
Common
Musculoskeletal:
Gastrointestinal:
Nephropathy
Neurosyphilis:
osteomyelitis
meningitis
deafness,
tinnitus
Secondary
Syphilis
Latent1
Late
Neurosyphilis
SECONDARY
Clinical
SYPHILIS
Findings
Figure
Differential
Diagnosis. The differential diagnosis of the
dermatologic manifestations of secondary syphilis is quite
extensive and should include pityriasis rosea, tinea
versicolor, erythema multiforme, drug eruption, viral
exanthems, psoriasis, ringworm, and scabies. The pale,
pinkish condylomata lata lesions tend not to be as raised as
the venereal warts of condyloma accuminata. Mucous
patches can be confused with herpes simplex lesions,
aphthous ulcerations, candidiasis, and Stevens-Johnson
syndrome. Both mucous patches and condylomata lata
contain spirochetes, which can be visualized by darkfield
examination.
LATENT
SYPHILIS
Clinical
Findings
LATE
Clinical
SYPHILIS
Findings
benign (or gummatous) syphilis, and neurosyphilis (see Box 641 ). Fewer organisms are found in lesions during this stage.
Cardiovascular
Syphilis. The incidence of cardiovascular
involvement is probably underestimated, although clinically
significant disease eventually develops in ~ 10% of all
untreated patients. Lesions include coronary ostial stenosis
and coronary artery insufficiency, aortic valvular
regurgitation with left ventricular hypertrophy and
congestive heart failure, and saccular aortic aneurysms of
the ascending and transverse portions of the thoracic aorta.
These aneurysms usually do not dissect and rupture but can
present as pulsating supraclavicular chest wall masses with
associated hoarseness, dysphagia, dyspnea, and cough due
to impingement on adjacent vital structures. Syphilis should
always be considered in patients whose chest radiograph
reveals ascending aortic calcifications or those with isolated
aortic valvular disease and positive treponemal serologies,
particularly if other manifestations of late disease are
present.
Late Benign Syphilis. The classic lesion of late benign
syphilis seen in ~ 15% of untreated patients is the gumma,
a granulomatous inflammatory process that usually affects
the skin, subcutaneous tissues, and bone but may involve
the liver, respiratory tract, stomach, heart, and almost any
other organ of the body. Usually nodular before ulcerating,
gummas are noninfectious, indurated, violaceous, and
painless. Gummas may heal or become chronic, resulting in
destructive local disease. The differential diagnosis includes
causes of other granulomatous processes such as
mycobacterial and fungal infections, sarcoidosis, and
malignancies.
Neurosyphilis
Clinically apparent CNS involvement is estimated to occur in
~ 510% of all syphilis patients and can be seen at any
stage of infection; however, early silent dissemination of T
neurosyphilis,
consequence
of
neuronal
CONGENITAL
Clinical
SYPHILIS
Findings
bossing, saddle nose, interstitial keratitis, notched and pegshaped upper Hutchinson's incisors (Figure 64-5 ), poorly
developed mulberry molars, anterior bowing of the lower
extremities,
perioral
and
P.675
Laboratory
Differential
Diagnosis. The differential diagnosis of
congenital syphilis includes other congenitally acquired
infections such as toxoplasmosis,
herpes simplex, and hepatitis B.
rubella,
cytomegalovirus,
Complications
Infants with untreated early syphilis may develop
manifestations of late congenital syphilis, as previously
described.
More
Common
lata
Hepatosplenomegaly
Fever
Dental abnormalities (Hutchinson's
molars)
Poorly developed maxilla
High palatal arch
Saddle nose
incisors,
mulberry
Frontal bossing
Interstitial
keratitis
See Box 64-1 (Acquired Syphilis in Adults)
Less Common
Lymphadenopathy
Aseptic meningitis
Meningovascular
syphilis
Pseudoparalysis
Nephropathy
Pneumonitis
Ascites
Mucous patch
Saber shins
Clutton's joints
Rhagades
Eighth nerve deafness
Flaring scapulae
Mental retardation
Hydrocephalus
See Box 64-1 (Acquired Syphilis in Adults)
1 Older than 2 years
Early
Congenital
Late
Congenital 1
Diagnosis
Acquired
techniques,
including
polymerase
chain
reaction,
requires
identification
of T pallidum in
Treatment
The drug of choice for all stages of syphilis is penicillin. Specific
treatment recommendations are dictated by the stage of
disease. Because of the organism's slow replication, prolonged
treponemicidal antimicrobial therapeutic levels are necessary.
Although alternatives to penicillin are available, nonpenicillinbased therapy is not recommended for patients who are
pregnant or have congenital syphilis, neurosyphilis, or HIV
coinfection.
Patients with spirochetal diseases may develop an acute
systemic reaction consisting of fever, chills, headache, and
myalgias within the first day after effective therapy. This
Jarisch-Herxheimer reaction is usually seen during treatment of
the earlier stages of syphilis, especially the secondary stage,
and resolves spontaneously after 1224 h. This reaction is
probably caused by the lysis of spirochetes with subsequent
release of antigen and toxic by-products. Symptomatic relief
with anti-inflammatory agents may be helpful.
The recommendations given in Boxes 64-3 , 64-4 , and 64-5 for
therapy and follow-up are based primarily on U.S. PHS
recommendations.
Incubating
Syphilis. Treatment of presumed incubating
syphilis with the same regimen prescribed for early syphilis
is recommended for all sexual contacts of patients with
primary, secondary, or early latent syphilis, within the prior
90 days. Although the use of multiple-dose azithromycin and
ceftriaxone appear promising in the treatment of early
syphilis, single-dose therapy with either agent for incubating
syphilis
requires
further
evaluation.
First
Choice
Choice
Allergic
Neurosyphilis
Syphilis
&
Pregnancy
Choice
Choice
Late 2
Neurosyphilis
First
Choice
Prophylactic
Measures
Precautions
Prevention
&
Control
REFERENCES
Abramowicz M, ed: Drugs for sexually transmitted diseases.
Med Lett Drugs Ther 1995;37:11722.
Berry MC, Dajani AS: Resurgence of congenital syphilis.
Infect Dis Clin North Am 1992;6:1929.
Centers for Disease Control and Prevention: 1998 guidelines
for treatment of sexually transmitted diseases. Morb Mortal
Wkly Rep 1998;47:2849.
Centers for Disease Control and Prevention: Summary of
notifiable diseases, United States 1997. Morbid Mortal
Weekly Rep 1997;46:187.
Centers for Disease Control and Prevention: Primary and
Secondary SyphilisUnited States, 1997. Morbid Mortal
Weekly Rep 1998;47:493497.
Fiumara NJ, Lessel S: Manifestations of late congenital
syphilis: an analysis of 271 patients. Arch Dermatol
1970;102:7883.
Fraser CM et al: Complete genome sequence of Treponema
pallidum , the syphilis spirochete. Science 1998;281:
375388.
337:30714.
St. Louis ME. Strategies for syphilis prevention in the
1990's. Sex Transm Dis 1996;23:5867.
Stoll BJ: Congenital syphilis: evaluation and management of
neonates born to mothers with reactive serologic tests for
syphilis. Pediatr Infect Dis J 1994;13:84553.
Tramont EC: Syphilis in adults: from Christopher Columbus
to Sir Alexander Fleming to AIDS. Clin Infect Dis
1995;21:136169.
2001
McGraw-Hill
> Table of Contents > Section V - Bacterial Infections > 65 Borrelia & Leptospira Species
65
Borrelia & Leptospira Species
Sandra Chaparro MD
Jose G. Montoya MD
BORRELIA
SPECIES
RELAPSING
Essentials
of
FEVER
Diagnosis
motile
(flagella).
General
Considerations
Clinical
Findings
Signs and symptoms. LBRF and TBRF have similar signs and
symptoms. The mean incubation period is 7 days (range, 218
days). Symptoms include sudden onset of fever, headache,
photophobia,
P.681
sweats, shaking chills, cough, nausea, vomiting, myalgias, and
arthralgias (Box 65-1). Common findings include conjunctival
suffusion, petechia, upper-quadrant abdominal tenderness, and
hepatosplenomegaly. Other complications include
gastrointestinal or CNS hemorrhage or both and myocarditis. A
Table
TBRF
Agent
Borrelia spp.
LBRF
Borrelia
recurrentis
Vector
Ornithodoros spp.
Pediculus
humanus
corporis
Reservoir
Rodents,
animals
Humans
Epidemiologic
Endemic
Epidemic
Distribution
Ethiopia,
South
America, Far
East
small
1 TBRF;
Laboratory
findings. LBRF and TBRF are established by the
detection of the spirochetes in blood from febrile patients.
Differential
Diagnoses
Treatment
Relapsing fever responds to doxycycline, tetracycline, erythromycin,
penicillin, and chloramphenicol (Box 65-2). One single dose of 500
mg of tetracycline (or erythromycin in children, pregnant patients,
or patients with penicillin allergies) for LBRF and a 10-day course
for TBRF are usually satisfactory. Antibiotic treatment can induce a
Jarisch-Herxheimer reaction within 2 h; this reaction coincides with
clearing of the spirochetes. This reaction is not prevented with
corticosteroids.
Acute
More
Common
Relapse
Fever
Rash
Headache
Shaking chills
Single
relapse with
LBRF
Multiples
Nausea, vomiting
Myalgias
Arthralgias
Cough
Conjunctival
injection
relapses
with TBRF
Petechia (more in
LBRF)
Hepatosplenomegaly
Less
Nuchal
rigidity
Common
(meningitis)
Pulmonary rales,
ronchi, pleuritic pain
Lymphadenopathy
Jaundice
Gastrointestinal
and
CNS hemorrhage
Myocarditis
Rupture of the spleen
1 LBRF,
Prognosis
With appropriate therapy, mortality rates from relapsing fever are <
5%. In untreated patients the fatality rate for LBRF may reach 40%,
and in TBRF is 5%.
Prevention
LBRF can be prevented with good personal hygiene,
P.682
delousing procedures, and secondary prevention with case detection
and treatment (Box 65-3). TBRF requires avoidance or elimination
of the tick, using acaricides.
Choice
Second
Choice
Pediatric
Considerations3
Doxycycline
mg
TBRF (7 day
course)
100
100 mg at
12-h
intervals
Tetracycline 500
mg
Erythromycin
500 mg
Chloramphenicol
500 mg
Penicillin G
(procaine) 600,
000 IU
500 mg at
6-h
intervals
500 mg at
6-h
intervals
500 mg at
6-h
intervals
600, 000
IU daily
Erythromycin
mg/kg/day
Penicilin G
40
mg/kg/day
10, 000
40
(procaine) 10,
000 IU/kg/day
IU/kg/day
Penicillin
Tetracycline
500 mg at
Allergic
mg
Erythromycin
500 mg
500
6-h
intervals
500 mg at
6-h
intervals
1 Antibiotic
relapsing
fever
3 Tetracycline
LYME
DISEASE
Essentials
of
Diagnosis
defects).
Serology is not standardized; it is insensitive in early infection
and does not distinguish active from inactive infection.
Grows in Barbour-Stoenner-Kelly medium from skin biopsy and
other specimens.
Polymerase chain reaction (PCR) can be useful in synovial-fluid
analysis. It has limited value with blood, cerebrospinal fluid
(CSF), and urine.
LBRF
personal
TBRF
Prophylactic
Good
Wear cloth
Measures
hygiene
Delousing
procedures
Improving
to protect
skin
Avoid
rodent- and
socioeconomic
conditions
(crowding,
poverty,
homelessness)
tick-infested
dwellings
Pest control,
repellents,
acaricide
1 LBRF,
General
Considerations
stages 2 and 3, which often affect the skin, joints, CNS, and heart.
However, any of the stages may fail to appear or may overlap with
one another (Table 65-2) .
Epidemiology. Lyme disease is the most
P.683
common vector-borne infection in the United States. In 1997,
there were 12,801 cases reported in the United States. It is
transmitted by ticks from the genus Ixodes. The Ixodes tick
goes through a 2-year life cycle that is composed of three
stages: larva, nymph, and adult. Tick larvae acquire the
spirochete via a blood meal from an infected host. Both the
nymph and female adult infect humans. A tick must be attached
for at least 24 h to transmit the spirochete. Tick engorgement
and attachment for 72 h are predictors of subsequent
human infection. Ixodes ticks in the northeastern and
midwestern United States belong to the Ixodes dammini
(scapularis)
pacificus, in
persulcatus.
of the larval
Table
Stage
Localized
migrans
erythema
Disseminated
Timing
chronicum
infection
Early
infection
Within days or
years
Persistent
infection
Months to years
More
Common
Adults)1
Less
Common
uveitis,
Clinical
Findings
lymphadenitis,
and
adult
respiratory
distress
syndrome.
Congenital
infection. Maternal-fetal transmission of B
burgdorferi has been reported with adverse fetal and
neonatal outcome in a few cases (congenital heart disease,
encephalitis, cortical blindness, intrauterine fetal death, and
premature birth). Of note, a prospective study found no
association between congenital malformation and infection
by B burgdorferi. Despite the fact that there is no definitive
proof that B burgdorferi causes fetal damage or an adverse
outcome in the offspring, prompt diagnosis in the mother
and treatment should be emphasized.
Laboratory
findings. The diagnosis of Lyme disease is made
on clinical findings, epidemiologic features, and an elevated
antibody response to B burgdorferi. The available laboratory
tests (with the exception of a positive culture from an EM
lesion) can be unreliable. Serologic testing only should be
undertaken when clinical and epidemiologic features suggest
Lyme disease as the diagnosis. Most patients with B burgdorferi
are found to have detectable antibodies when tested with
enzyme-linked immunosorbent assay (6070% within 24
weeks of infection and 90% by the disseminated and persistent
stages). However, serologic tests lack standardization, their
accuracy is often unsubstantiated, and false-positive results are
common. IgM antibody appears 24 weeks after the EM
lesion, peaks at 68 weeks, and declines after 46 months.
IgG antibody appears 68 weeks after the EM lesion, peaks at
46 months, and remains at low levels despite antibiotic
therapy. A fourfold rise in antibody titer would be suggestive of
recent infection. Western blot analysis is used to confirm results
obtained by enzyme-linked immunosorbent assay. The finding
that a patient has significant amounts of anti-B
burgdorferispecific antibodies can be interpreted only in the
context of the clinical setting. Demonstrating that a patient has
an immune response against this organism does not mean that
the patient is actively infected or that any symptoms are
necessarily related to B burgdorferi infection. Detection of
Differential
Diagnosis
Table
Stage
Localized
Infection
Clinical
manifestation
Erythema
chronicum
migrans
Other
diagnoses
Streptococcal
cellulitis
Erythema
multiforme
Erythema
marginatum
Tinea corporis
(ringworm)
Nummular eczema
Granuloma
Disseminated
Infection
7th nerve
palsy
annulare
Carditis
Endocarditis
Meningitis
Viral meningitis
Parameningeal
infections
Postinfectious
meningoencephalitis
Leptospiral
meningitis
Tuberculous
meningitis
Listeria partially
treated
Bacterial
(pyogenic)
meningitis
Subacute (to
chronic) meningitis
Arthritis
Acute rheumatic
fever
Malignant effusion
Post-traumatic
effusion
Hemophilia
Pyogenic arthritis
Persistent
Arthritis
Infection
Juvenile
rheumatoid
arthritis
Henoch-Schnlein
purpura
Serum sickness
Collagen vascular
disease
Psoriatic
arthritis
Postinfectious
arthritis
Behet's disease
Chronic fatigue
syndrome
1 CNS,
Treatment
Early disease responds readily to several oral agents (such as
doxycycline, amoxicillin, or cefuroxime), which are usually
prescribed for 23 weeks (Box 65-5). There are few published,
controlled trials that compare different regimens for late Lyme
disease. Intravenous therapy, usually ceftriaxone or penicillin, is
used for 23 weeks for late Lyme disease.
Erythema migrans. In EM, oral antibiotic therapy with
doxycycline shortens the duration of the rash and prevents the
development of late sequelae. Amoxicillin is also effective and
preferred for children under 9 years of age and in pregnant or
lactating women.
Musculoskeletal
disease. Treatment for one month with oral
doxycycline or amoxicillin is usually effective. For refractory
Oral
First
Choice
Second
Choice
Therapy
Intravenous
therapy
Doxycycline,
100 mg twice
per day
Amoxicillin,
500 mg three
times per day
Ceftriaxone,
2000 mg
daily
Clarithromycin,
500 mg twice
per day
Azithromycin,
Cefotaxime,
2000 mg at
8-h intervals
Penicillin G,
500 mg daily
Cefuroxime,
500 mg twice
5 million IU
at 6-h
intervals
per day
Pediatric
Considerations1
Amoxicillin, 50
mg/kg/day
Ceftriaxone,
75
mg/kg/day
Penicillin G,
300, 000
IU/kg/day
Penicillin
Allergic
1 Tetracycline
Clarithromycin,
500 mg twice
Doxycycline,
100 mg twice
per day
Azithromycin,
500 mg daily
per day
Azithromycin,
500 mg daily
Prognosis
Most patients treated promptly with an appropriate antibiotic have
an uncomplicated course. True failures are rare, and in most cases
re-treatment or prolonged treatment is the result of misdiagnosis
and misinterpretation of serologic results rather than inadequate
therapy.
Pr o p h yl a x i s
Routine use of antimicrobial prophylaxis after a tick bite is not
recommended. However, some experts recommend amoxicillin for
pregnant women who remove an engorged deer tick after exposure
in an endemic area. Persons who develop a rash or illness within a
month after a tick bite should seek prompt medical attention.
Strategies to prevent Lyme disease include avoiding tick habitats,
LEPTOSPIRA
Essentials
of
SPECIES
Diagnosis
Prophylactic
Measures
Isolation
Precautions
Repellents,
insecticides
Check for ticks every 24 h
More
Common
Anicteric
Septic phase: (37 d) Fever, headache,
myalgias, abdominal pain, nausea,
vomiting
Immune phase: (0 d1 mo) Lower fever,
intense headache, aseptic meningitis,
conjuctival injection, uveitis,
hepatosplenomegaly,
pulmonary
involvement, skin rashes
Less
Common
Icteric
Septic phase: (37 d)
Imune phase: (1030 d) Jaundice, renal
dysfunction, vasculitis, pulmonary
hemorrhage,
myocarditis
General
Considerations
Anicteric
First
Choice
Second
Choice
Pediatric
Considerations1
Icteric
Ampicillin,
500 mg four
times daily
Penicillin G,
1.5 million IU
four times
by mouth
Amoxicillin,
500 mg four
times daily
daily
intravenously
Ampicillin,
1000 mg four
by mouth
Doxycycline,
100 mg four
times daily
times daily
intravenously
Amoxicillin,
1000 mg four
by mouth
times daily
intravenously
Tetracycline,
2000 mg/day
by mouth
Erythromycin,
2 500 mg four
times daily
intravenously
Ampicillin, 50
mg/kg/day
by mouth
Amoxicillin,
50
Penicillin G,
68 million
IU/m2 day
intravenously
Erythromycin,
Penicillin
Allergic
mg/kg/day
by mouth
Doxycycline,
100 mg four
times daily
by mouth
Erythromycin,
2 500 mg four
times daily
intravenously
50
mg/kg/day
intravenously
1 Tetracycline
Clinical
Findings
Laboratory
findings. Laboratory findings in anicteric
leptospirosis include normal leukocyte counts with neutrophilia
and elevated ESR and CSF protein. Pulmonary and myocardial
involvement; high bilirubin levels; increases in alkaline
phosphatase, aspartate aminotransferase, alanine
aminotransferase, creatine phosphokinase, creatinine, and blood
urea nitrogen; and
icteric leptospirosis.
organism from any
fourfold increase in
Prophylactic
Measures
Isolation
Precautions
Differential
Diagnoses
Complications
Aseptic meningitis is the most common complication in the anicteric
cases. Renal failure, liver damage, pulmonary hemorrhage,
vasculitis, and myocarditis are less common but are the usual
causes of death.
Treatment
Penicillin G or doxycycline are effective even when treatment is
delayed (Box 65-8). Penicillin G or ampicillin should be used in
severely ill patients. In less severely ill patients, an oral dose of
ampicillin, doxycycline, or amoxicillin can be used.
Prognosis
In the absence of jaundice, the disease is rarely fatal. The mortality
rate in icteric patients under 30 years of age is 5%; in the elderly
the rate is 3040%.
Prevention
Doxycycline can prevent infection (Box 65-9). However, prevention
is problematic because exposure is difficult to predict. Effective rat
control and avoidance of infected urine and known contaminated
water sources are important preventive measures.
REFERENCES
Cadavid D, Barbour AG: Neuroborreliosis during relapsing fever:
Review of the clinical manifestations, pathology and treatment of
infections in humans and experimental animals. Clin Infect Dis
1998;26:151.
2001
McGraw-Hill
&
Ureaplasma
66
Mycoplasma
&
Ureaplasma
Jose G. Montoya MD
Mycoplasma and Ureaplasma species (mycoplasmas) are
ubiquitous in nature and are commonly found in plants, animals,
and humans. These bacteria contain the smallest amount of
double-stranded DNA that is capable of producing a free-living
microorganism; they measure between 0.15 and 0.3 m in
diameter and 2 m in length. They are believed to have
evolved from a putative common ancestor of the gram-positive
bacteria by a process of genome reduction and adoption of a
dependent, parasitic life style. Mycoplasma and Ureaplasma spp.
lack a cell wall. Therefore, they cannot be visualized with the
Gram stain and are not susceptible to antibiotics that act on cell
wall synthesis (eg, penicillins and cephalosporins). They are
capable of growing in cell-free media, but require many
exogenous nutrients for growth, including sterols. In addition to
Ureaplasma
urealyticum, 13 species of Mycoplasma have been
isolated from humans; however, most of them are not regarded
as pathogens.
Mycoplasmas are the etiologic agents and cofactors of several
clinical syndromes in humans. Mycoplasma
pneumoniae is a
common cause of community-acquired pneumonia. U
Essentials
Community
of
Diagnosis
acquired
Extrapulmonary
pneumonia.
involvement
is
not
infrequent.
bacterial
Coombs-positive
type.
hemolytic
anemia.
General
Considerations
urealyticum
Clinical
Respiratory
Findings (Box
66-1)
Involvement.
associated
with M
pneumoniae
infection.
pneumoniae Disease
More
Common
Tracheobronchitis
Pneumonia
Less
Common
Erythema
multiforme
Stevens-Johnson
syndrome
Raynaud's
phenomenon
Congestive heart failure,
myopericarditis,
hemopericardium
Aseptic
meningitis,
meningoencephalitis
Transverse
myelitis
Guillain-Barr
syndrome,
peripheral
neuropathy
Diagnosis
Methods
for
diagnosing M
Differential
Diagnosis
Treatment
The efficacy of antimicrobial agents in patients with M
Prevention
There are currently no recommended specific control measures
for M pneumoniae outbreaks in closed communities. However,
some studies have suggested the usefulness of prophylactic
antibiotics administered to close contacts of case patients. One
study demonstrated that the administration of azithromycin,
500 mg on day 1 and 250 mg on days 25, to individuals at
risk was beneficial in reducing the disease attack rate during an
institutional outbreak of M pneumoniae pneumonia. There is no
available vaccine.
First
Choice
pneumoniae
Second
Choice
Pediatric
Considerations
1 Cell
P.693
INFECTIONS CAUSED BY U
UREALYTICUM & OTHER
MYCOPLASMAS
U urealyticum, M hominis, and M genitalium are commensals of
the genitourinary tract of both women and men and in
newborns. U urealyticum is an infrequent cause of urethritis in
males, urinary calculi, chorioamnionitis, spontaneous abortion,
and premature birth. M genitalium is also associated with male
urethritis. M hominis is a rare cause of pyelonephritis, pelvic
inflammatory disease, and postabortal and postpartum fevers.
U urealyticum and M hominis can cause disease outside the
genitourinary tract in immunosuppressed patients or in
otherwise immunocompetent patients after manipulation or
trauma of the genitourinary tract. M hominis can cause sternal
wound infections and osteomyelitis, arthritis (especially in
hypogammaglobulinemic patients), brain abscess, pneumonia,
and peritonitis. It has been associated with neonatal pneumonia
and sepsis. In immunosuppressed patients, U urealyticum can
cause arthritis, osteomyelitis, sinusitis, and pneumonia. It can
also cause neonatal pneumonia and sepsis.
A thorough search for other causes should be completed before
U urealyticum or M hominis can be considered the etiologic
agent of any of the above syndromes.
Mycoplasma penetrans, Mycoplasma pirum, and Mycoplasma
fermentans have been associated with HIV infection and with
the progression to AIDS; however, there is little evidence for a
causal role of these organisms in this disease process. The
associations more likely reflect the enhanced susceptibility of
the HIV-infected host to secondary mycoplasma infection.
M hominis can be treated with tetracyclines or with clindamycin.
U urealyticum infections can be treated with tetracyclines,
erythromycin, or azithromycin. Both U urealyticum and M
REFERENCES
Fenollar F et al: Mycoplasma infections of aneurysms or
vascular grafts. Clin Infect Dis 1999;28:694.
Hutchison CA et al: Global transposon mutagenesis and a
minimal Mycoplasma genome. Science 1999;286:2165.
Klausner JD et al: Enhanced control of an outbreak of
Mycoplasma
pneumoniae pneumonia with azithromycin
prophylaxis. J Infect Dis 1998;177:161.
Razin S, Yogev D, Naot Y: Molecular biology and
pathogenicity of mycoplasmas. Microbiol Mol Biol Rev 1998;
62:1094.
Rottem S, Naot Y: Subversion and exploitation of host cells
by mycoplasmas. Trends Microbiol 1998;6:436.
2001
McGraw-Hill
67
Chlamydia
Jose G. Montoya MD
General
Considerations
Diagnosis
Chlamydial infections require laboratory studies for a definitive
diagnosis. Available laboratory techniques include cytology,
culture, serology, and demonstration of chlamydial antigens or
nucleic acid sequences.
Treatment
Antimicrobial agents such as the tetracyclines, certain
macrolides, and some fluoroquinolones are highly active against
Chlamydia infections. Clinically relevant resistance to these
antibiotics has not been observed. All sex partners of patients
with sexually transmitted chlamydial infections should be
referred for evaluation and treatment.
TRACHOMATIS
Essentials
of
INFECTIONS
Diagnosis
in
Giemsa-stained
cell
Clinical
Syndromes
suspected epididymitis,
should be ruled out.
out testicular torsion include
medicine studies. In
rate
or
C-reactive
More
Common
Mucopurulent
cervicitis
Acute salpingitis1
Endometritis1
Bartholinitis
Acute urethral syndrome
Nongonococcal
Postgonococcal
urethritis
urethritis
Epididymitis
Inclusion
conjunctivitis
in
infants
Pneumonia in infants
Less
Common
Perihepatitis
Proctitis
Conjunctivitis
Reiter's syndrome
Proctitis
Conjunctivitis
Reiter's
syndrome
Otitis media
C trachomatis in genital secretions should raise the
suspicion of sexual abuse
1
Men
Children
trachomatis
Infections
Diagnosis
Urethritis. In men with suspected nongonococcal or
postgonococcal urethritis, the diagnosis of urethritis should
be confirmed based on the results of urinalysis with
10 leukocytes per high-power field or on Gram stain
examination of the urethral discharge revealing > 4
neutrophils per oil immersion field. The absence of N
gonorrhoeae should be documented with a properly
performed Gram stain examination of the urethral material.
Proctitis,
and
Mucopurulent
Cervicitis. In
test
for C
trachomatis is indicated.
Treatment
Urethritis. Adults with NGU or PGU should be treated as
soon as possible after diagnosis. A single-dose regimen
based on azithromycin for example has the important
advantage of improved adherence (Box 67-2 ). Doxycycline,
erythromycin, or ofloxacin can also be used. Ofloxacin is
also often effective against N gonorrhoeae. Other drugs
used against N gonorrhoeae such as the cephalosporins and
are
contraindicated
in
Lymphogranuloma
Venereum. LGV is treated with
doxycycline (Box 67-3 ). Alternative drugs include
macrolides such as erythromycin. The activity of
azithromycin
against C trachomatis suggests that it may be
effective in treating LGV given in multiple doses over 23
weeks, but clinical data regarding its use for this disease
are lacking.
Patients with suspected or proven C trachomatis infection
should be instructed to refer their sex partners (sexual
contacts during the 60 days preceding
P.699
First
Choice
Choice
Considerations3
First
Choice
Choice
Inclusion
Conjunctivitis1
trachomatis
Infections
Prevention
Programs aimed at the detection of asymptomatic chlamydial
infection and treatment of both symptomatic and asymptomatic
cases have proven to be effective in decreasing the prevalence
PSITTACI
Essentials
of
INFECTIONS
Diagnosis
-specific
microimmunofluorescence
Clinical
Findings
Diagnosis
The diagnosis of psittacosis can be confirmed by isolation of C
psittaci or by serological tests. However, owing to its fastidious
growth requirements and the associated hazards of its growth to
Common
Community-acquired
pneumonia
with
nonproductive
cough,
Common
and
pericarditis
Treatment
Patients with C psittaci infection should be treated with a
tetracycline (Box 67-6 ). Patients usually respond with
amelioration of their symptoms within 2448 h after
institution of therapy. In patients allergic to or intolerant of
tetracyclines, erythromycin can be used as an alternative.
The recommended treatment of psittacosis in children 8
years of age is 500 mg of tetracycline every 6 h, orally, for
710 days. Erythromycin also can be used (50 mg/kg/d up to
2 g/d for 710 days). Tetracycline may be more effective than
erythromycin.
Prevention
Imported birds should be quarantined and treated with a
tetracycline for 30 days. An additional course of tetracycline for
15 days should be given by the importers or owners. Some birds
will still shed the organism if treatment courses of < 45 days
are used.
PNEUMONIAE
Essentials
of
Hoarseness
Positive C
may
INFECTIONS
Diagnosis
accompany
pneumoniae
atypical
-specific
pneumonia.
microimmunofluorescence
serologies.
Positive complement fixation titers (not species specific).
P.701
Isolation and PCR techniques available in research
laboratories only.
First
Choice
Choice
Considerations
More
Common
Infections
Community-acquired
Possible association
disease
pneumonia
with atherosclerotic
cardiovascular
Common
Bronchitis
Pharyngitis
Sinusitis
Endocarditis
Lumbosacral
meningoradiculitis
Erythema nodosum
Encephalitis
BOX 67-7 C
Clinical
Upper-
and
Findings
lower-respiratory-tract
infections
including
sinusitis,
Choice
Choice
Considerations
pneumoniae
Infections
Diagnosis
Serological methods are commonly used for the diagnosis of C
pneumoniae infections. They are rarely helpful in the acute
setting, and they are mostly used for surveillance purposes.
Complement fixation methods do not differentiate among
infections caused by C trachomatis, C psittaci , and C
pneumoniae. Microimmunofluorescence methods detect C
pneumoniae -specific antibodies and are the approaches most
commonly used in clinical practice. Acute and convalescent sera
samples obtained 34 weeks apart should be analyzed
in parallel. Isolation of this organism and PCR-based methods
are not routinely performed outside research laboratories.
Treatment
REFERENCES
Campbell LA, Kuo CC, Grayston JT: Chlamydia
pneumoniae
and cardiovascular disease. Emerg Infect Dis 1998;
4(4):571.
P.702
Centers for Disease Control and Prevention: Compendium of
measures to control Chlamydia psittaci infection among
humans (psittacosis) and pet birds (avian
chlamydiosis),1998. Morb Mortal Wkly Rep 1998;47(RR10):1.
Centers for Disease Control and Prevention: 1998 Guidelines
for treatment of sexually transmitted diseases. Morb Mortal
Wkly Rep 1998;47(RR-1):1.
Gaydos CA et al: Molecular amplification assays to detect
chlamydial infections in urine specimens from high school
female students and to monitor the persistence of chlamydial
DNA after therapy. J Infect Dis 1998;177: 417.
Gregory DW, Schaffner W: Psittacosis. Sem Resp Infect
1997;12(1):7.
Kalman S et al: Comparative genomes of Chlamydia
pneumoniae and C trachomatis. Nat Genet 1999;21:385.
2001
McGraw-Hill
Ehrlichia,
&
Rickettsia
68
Coxiella,
Ehrlichia,
&
Rickettsia
COXIELLA
FEVER )
Essentials
Acute
BURNETII INFECTION (Q
of
Diagnosis
Infection
acute
febrile
illness,
pneumonitis,
Infection
endocarditis;
General
Considerations
Clinical
Findings
More
Common
Flulike
illness
Pneumonitis
Hepatitis
Less
Common
Diagnosis
The diagnosis of Q fever is based on an appropriate clinical
history, along with a clear or possible history of animal
exposure. The bacteria can be cultured from the blood, urine,
and sputum by inoculation into chicken embryos or cultured
human fibroblasts, but this procedure requires a specialized
laboratory. In addition, the risk of transmission to laboratory
workers is high; therefore, it should only be attempted in
laboratories with considerable experience in handling this
organism. The routine approach for the diagnosis of Q fever is a
serological one, with detection of antibody to phase-I and -II
antigens. Complement fixation, indirect fluorescent antibody
(IFA), and enzyme-linked immunosorbent assays are available.
Acute Q fever is diagnosed by a fourfold or greater increase in
levels of antibodies directed against the C burnetii phase-II
antigens. Titers become positive by 814 days after onset of
the illness and peak at 48 weeks using IFA testing or at
1213 weeks using complement fixation testing. Chronic
disease, eg, endocarditis, is diagnosed by detecting levels of
antibodies to C burnetii phase-I antigens in excess of levels of
antibodies directed against the phase-II antigens. A complement
fixation antibody titer against the phase-I antigens of >1:200 is
considered also diagnostic.
First
Choice
Choice
24
g/day
Considerations
Penicillin
Allergic
As above
As above
Children
Adults
Treatment
Acute Q fever is usually self-limited. However, antimicrobial
agents are recommended to prevent the development of chronic
infection and possibly to decrease the duration of symptoms
(Box 68-2 ). Doxycycline is effective, provided that it is started
early in the disease. Quinolones, because of their cerebrospinal
fluid penetration, should be considered for the treatment of
meningoencephalitis. Treatment of chronic Q fever has never
been studied in a controlled setting. Recommended regimens
include rifampicin or ciprofloxacin plus doxycycline (Box 68-3 ).
The duration of therapy necessary for a cure is also unknown,
but 12 months is required, and some experts recommend a
minimum of 3 years. In many cases, lifelong treatment may be
necessary. Current studies are assessing the use of
hydroxychloroquine in conjunction with doxycycline and/or
ciprofloxacin, since blockade of intracellular acidification with
Prevention
&
Control
EHRLICHIA INFECTION
(EHRLICHIOSIS)
Essentials
of
Diagnosis
leukopenia,
and
First
Choice
OR
Doxycycline as above
PLUS
TMP/SMX
OR
Rifampicin
OR
Chloroquine
Doxycycline, 100 mg twice daily for 3 years, perhaps for life
OR
Doxycycline as above
PLUS
TMP/SMX
OR
Rifampicin
OR
Chloroquine
Pediatric
Considerations
Tetracycline should not be used in children <8 years old
Fluoroquinolones should not be used in children and
adolescents <18 years old
Children
Adults
General
Considerations
Clinical
Findings
More
Common
Flulike
illness
Common
Diagnosis
It is necessary and important to consider the diagnosis of
ehrlichiosis based only on epidemiological and clinical features,
to facilitate administration of empiric therapy, because there is
no widely available rapid diagnostic test other than detection of
visible morulae. Ehrlichiosis should be considered in any febrile
patient in an endemic region with exposure to ticks within the
preceding 3 weeks. The diagnosis becomes more likely if
thrombocytopenia, elevated hepatic transaminases, or
leukopenia is present. There are no absolute clinical criteria that
distinguish ehrlichiosis from RMSF, although patients with
ehrlichiosis are less likely to have a rash and more likely to
have leukopenia and elevated hepatic transaminases. In
addition to finding intraleukocytic morulae, serology offers a
reliable but retrospective method for diagnosing Ehrlichia
infection. Acute and convalescent titers are required. IFA
detection assays are available for both HME and HGE. Although
E chaffeensis and the agent of HGE can be cultured, this method
of detection and PCR-based assays are not widely available.
Treatment
Doxycycline is the agent of choice for both HGE and HME (Box
68-5 ). The clinical response is rapid, usually within 2448 h.
Chloramphenicol has been used in younger children to prevent
teeth discoloration secondary to tetracyclines; however, in vitro
and in vivo failures have been described. Enhanced mortality
and morbidity from ehrlichiosis are associated with delayed
administration of appropriate therapy, advanced age, and a
higher percentage of infected
P.708
leukocytes. Although most patients respond to therapy within
several days, most experts advocate a 14-day course of
therapy, in part to treat more adequately for possible
concomitant Borrelia
burgdorferi infection.
First
Choice
concomitant
Lyme
disease)
Choice
Considerations
Children
Adults
Prevention
&
Control
RICKETTSIAL
INFECTIONS
ROCKY
MOUNTAIN
Essentials
of
SPOTTED
FEVER
Diagnosis
General
Considerations
Clinical
Findings
More
Common
Common
Conjunctival
suffusion
Photophobia
Cough
Mental confusion,
obtundation
Diagnosis
Confirmatory serology is retrospective in nature; therefore, the
physician must have a high index of suspicion based on clinical
findings to start therapy. There are no diagnostic laboratory
tests other than specific serologic and PCR-based tests. The
leukocyte count is usually slightly decreased or normal, but an
elevated band count of >10% is seen in 69% of patients.
Thrombocytopenia occurs in 52% of patients, and 32% will have
platelet counts of <100,000/ml3 . Other abnormalities include
hyponatremia and elevated serum aminotransferase and
bilirubin levels. A PCR assay for RMSF using whole blood is now
available through state health
P.710
departments or the Centers for Disease Control and Prevention.
None of the currently available serologic tests are useful for
diagnosis in the acute phase of illness. The most sensitive and
specific serologic assay is an IFA test. A diagnostic titer of >64
is usually detectable between 7 and 10 days after the onset of
symptoms. The less sensitive latex agglutination test is more
widely available and will demonstrate a rise in titer to >128,
79 days after the onset of symptoms. Immunohistologic
Treatment
Doxycycline is the drug of choice for the treatment of RMSF,
except in cases of pregnancy and drug allergy or in children <9
years of age (Box 68-7 ). Although chloramphenicol has been
recommended in these groups, many experts feel that it is safe
to give a short course of doxycycline for the treatment of a
potentially life-threatening infection in children <9 years old.
The likelihood of permanent tooth staining from a short course
of doxycycline is very low. Although there are in vitro data
indicating that fluoroquinolones may be efficacious, these
agents have not been widely used in the treatment of RMSF and
cannot be recommended at this time. Treatment is continued for
2 days after defervescence to reduce the risk of relapse. If
therapy is started early, most patients defervesce within 48 to
72 h. Severely ill patients treated late in the course of disease
may take considerably longer to recover.
Prevention
Avoidance of tick bites is the best method of prevention.
Protective clothing, tick repellents, and careful total body
inspection can reduce the risk of inoculation. Prompt removal of
ticks with forceps by firm traction is the preferred method. It is
essential not to crush the tick so as to prevent release of
rickettsiae.
First
Choice
Second
Choice
Considerations
Children
Adults
RICKETTSIALPOX
Essentials
of
Diagnosis
lymphadenopathy.
General
Considerations
Clinical
Findings
A painless papule develops 714 days after the mite bite. The
papule then becomes vesicular, dries, crusts over, and evolves
into a black eschar. The onset of clinical illness, characterized
by abrupt onset of high fever, sweats, headache, myalgias, and
malaise, occurs 47 days after the appearance of the initial
papule. The systemic symptoms are usually mild, but, if
untreated, the patient will have daily temperature elevations up
to 3939.5C for 710 days. A maculopapular rash
appears at the onset of fever and quickly becomes vesicular.
The vesicles are small and nonpruritic, and they may be
numerous or few. Within a week, the vesicles
P.711
crust over and disappear with no sequelae. The diagnosis is best
established by the epidemiologic history, the presence of a
primary eschar, and a serum IFA test. Therapy with doxycycline
or chloramphenicol is effective (see Treatment section for Rocky
Mountain spotted fever ). Preventive steps involve eliminating
house mice and their mites.
OTHER
SPOTTED
FEVERS
ENDEMIC
(MURINE)
TYPHUS
EPIDEMIC
(LOUSE-BORNE)
TYPHUS
prowazekii.
SCRUB
TYPHUS
Orientia
tsutsugamushi causes scrub typhus; it is transmitted by
the bite of an infected mite. The disease is found in Southeast
Asia, India, and northeastern Australia. Symptoms and signs of
disease consist of an eschar at the bite site, regional and then
REFERENCES
Coxiella
Ehrlichia
Infection
(Ehrlichiosis)
Rocky
Mountain
Spotted
Fever
Rickettsialpox
Comer JA et al: Serologic evidence of rickettsialpox
(Rickettsia akari ) infection among intravenous drug users in
inner-city Baltimore, Maryland. Am J Trop Med Hyg
1999;60(6):894.
Kass EM et al: Rickettsialpox in a New York City hospital,
19601989. N Engl J Med 1994;331:1612.
Endemic
(Murine)
Typhus
Epidemic
(Louse-Borne)
Typhus
2001
McGraw-Hill
69
Bartonella
Phyllis C. Tien SM, MD
Jeffery S. Loutit MB, ChB
Essentials
of
Diagnosis
General
Considerations
lymphocytic
infiltrates
and
multinucleated
resembles
bacillary
angiomatosis.
More
Common
Children
Adults
Bacillary
angiomatosis
Persistent
bacteremia
and/or
endocarditis
Less
Bacillary
bacilliformis -
Common
angiomatosis
Persistent
bacteremia
and/or
endocarditis
associated
disease
Cat scratch
disease
B bacilliformis associated
disease
CLINICAL
BACILLARY
SYNDROMES
ANGIOMATOSIS
Table
Bacillary
Angiomatosis
Neovascular
proliferative
lesion, primarily of skin
Liver and spleen involvement
leads to bacillary peliosis
May affect mucous
membranes, lung, bone, and
CNS
bacilliformis
Infection
Cat Scratch
Disease
Erythematous papule 35
days after cat contact at
inoculation site
Proximal
lymphadenopathy
usually of head, neck, or
upper extremity
Lymph nodes may suppurate
Fever and
Bacteremia
Endocarditis is sometimes
associated
Trench fever associated with
B. quintana bacteremia
CAT
SCRATCH
Clinical
DISEASE
Findings
infectious mononucleosis,
and brucellosis.
tularemia,
B
BACILLIFORMIS-ASSOCIATED
DISEASE
About 3 weeks after the bite of an infected sandfly, acute B
bacilliformis infection becomes manifest as a febrile bacteremic
illness (Oroya fever). It is accompanied by an acute hemolytic
anemia that is caused by bacterial attachment and invasion of
erythrocytes (Table 69-1). Patients exhibit malaise, fever,
chills, diaphoresis, headache, and mental status changes.
Lymphadenopathy,
hepatosplenomegaly,
and
thrombocytopenia
are also seen. At the end of the acute bacteremic phase, there
is a transient immunosuppression that renders the patient
susceptible to a wide range of opportunistic bacterial, viral, and
parasitic secondary infections. Mortality during this acute phase
Diagnosis
Difficulty in the identification and isolation of Bartonella species
from blood and tissue has made a diagnosis of infection with
of
Treatment
Treatment of Bartonella-associated disease varies according to
the clinical syndrome (Box 69-2). All recommendations are
based on anecdotal evidence of treatment response since
controlled trials have not been performed.
Bacillary angiomatosis should always be treated. Spontaneous
resolution of superficial skin papules has been reported, but
relapse and bacterial dissemination are common. Nevertheless,
therapeutic endpoints remain undefined.
Anecdotal evidence strongly favors the use of oral erythromycin
for treatment of bacillary angiomatosis at a dose of 500 mg four
times per day for 812 weeks. Intravenous erythromycin
should be administered to patients with severe disease or
patients who are unable to take oral medications. Longer
courses may be necessary in patients with
bacteremia/endocarditis or bacillary peliosis and those with
disease recurrence. The newer macrolides, azithromycin and
clarithromycin, may also be effective, but experience with these
First
Cat
Scratch
Choice
Infections
Second
Choice
Symptomatic
Azithromycin,
Disease
therapy (resolves
spontaneously)
500 mg PO once
on the first day,
and 250 mg
once daily for
four subsequent
days
Bacillary
Angiomatosis
Erythromycin,
500 mg PO 4
times a day for at
least 8 wks a
Doxycycline,
100 mg PO
twice daily for
at least 8 wks1
B
bacilliformis
Chloramphenicol
(recommended in
Infection
endemic
regions)
Fever and
Bacteremia
Erythromycin,
500 mg PO4
times a day for at
least 4 wks 1
1 Longer
Prevention
&
Control
Prophylactic
Measures
Infections
Isolation
None
Precautions
P.719
REFERENCES
Anderson BE, Neuman MA: Bartonella spp. as emerging
human pathogens. Clin Microbiol Rev 1997;10(2):203.
Loutit JS. Bartonella infections. Curr Clin Topics Infect Dis
1997;17:269.
Maurin M, Raoult D: Bartonella
Microbiol Rev 1996;9(3):273.
2001
McGraw-Hill
70
Histoplasma
capsulatum
Zelalem Temesgen MD
Essentials
of
Diagnosis
General
Considerations
Epidemiology. Histoplasma
capsulatum , the etiologic agent of
histoplasmosis, is an endemic, dimorphic fungus that causes a
wide spectrum of disease in both immunocompetent and
immunocompromised individuals. It is found in temperate zones
around the world. In the United States, it is endemic within the
Ohio and Mississippi River Valleys. Its natural habitat is soil,
especially soil with high organic content such as soil enriched
with bird, chicken, and bat excrement. Many types of both
occupational and recreational activities (eg, cave exploring,
excavation) have resulted in outbreaks of histoplasmosis.
Microbiology. H capsulatum is dimorphic; it grows as a mycelial
form outside the human host but converts into its pathogenic
yeast form at the body temperature of mammals. The yeast
forms seen in tissue are small, thin-walled, oval structures
measuring 24 mm in diameter.
Pathogenesis. The vast majority of infections caused by H
capsulatum are acquired by inhalation and deposition of mycelial
fragments into the alveoli. The organism converts into its
pathogenic yeast form and is phagocytosed by alveolar
macrophages. The yeast forms multiply within the macrophages,
eventually causing the destruction of these macrophages. The
released yeasts spread to the regional lymph nodes and other
organs via the lymphatics and blood. Specific T cell-mediated
immunity develops in 24 weeks and inhibits the growth of the
organisms. Resolution occurs with production of a granulomatous
inflammatory response and leads to the formation of granulomas,
which may be caseating but usually become calcified. The yeasts
persist for prolonged periods within caseating granulomas.
CLINICAL
SYNDROMES
PULMONARY
1.
ACUTE
Clinical
INFECTIONS
PRIMARY
HISTOPLASMOSIS
Findings
More
Common
histoplasmosis
2.
CHRONIC
Clinical
PULMONARY
HISTOPLASMOSIS
Findings
pulmonary
histoplasmosis
3.
MEDIASTINAL
GRANULOMATOSIS
4.
FIBROSING
MEDIASTINITIS
DISSEMINATED
HISTOPLASMOSIS
findings.
HISTOPLASMOSIS
Clinical
IN
AIDS
Findings
anemia, thrombocytopenia),
enzymes. Lymphadenopathy
present.
First
intravascular
coagulopathy,
and
Choice
Choice
200400
mg/daily
Immunocompromised
Patients
Central
Nonmeningeal,
Nervous
System
Disease
Non-LifeThreatening
Disease
AIDS
Patients
Diagnosis
Histoplasmosis can be diagnosed on the basis of serologic testing,
antigen detection, histopathological examination, or culture.
Serology. Serologic tests provide important supplemental
information in cases where proof of infection cannot be obtained
through culture or histopathological examination. Currently, the
complement fixation and immunodiffusion tests are the serologic
tests that are most commonly employed.
Complement Fixation Test. Complement fixation antibodies
may be detected at ~ 3 weeks after acquiring infection and wane
over several months. In chronic or disseminated infection, they
might remain elevated for years. Titers of 1:32 or greater may be
indicative of active infection. Titers of 1:8 or 1:16 should raise
suspicion for infection. Cross-reaction may occur with
blastomycosis and coccidiomycosis, but in these instances, titers
are usually lower.
Immunodiffusion. Immunodiffusion assays detect antibodies to
two glycoprotein antigens, designated M and H antigens.
Antibodies to M and H antigens appear later in infection than
complement fixation antibodies. Anti-M antibodies may persist for
years after acute infection. Anti-H antibodies are detected later
than antibodies to M antigen and also disappear earlier. Thus
weeks).
Treatment
Amphotericin B is the drug of choice for immunocompromised
patients and for patients with life-threatening disease or central
nervous system disease (Box 70-2 ). For nonmeningeal, non-lifethreatening histoplasmosis, the triazole antifungal agent itraconazole
has become the preferred agent. It has supplanted the previous azole
mainstay of therapy, ketoconazole, because of its lower incidence of
side effects and increased efficacy.
Precautions
Individuals who are at risk (eg, immunocompromised, HIV-infected)
should avoid activities associated with acquiring infection, such as
cleaning chicken coops and exploring caves
Prophylaxis
Prophylaxis with itraconazole may be conisdered for AIDS
patients living in endemic areas
AIDS patients with histoplasmosis who have completed intitial
therapy should receive lifelong suppressive treatment with
itraconazole.
BOX 70-3 Control of Histoplasmosis
Histoplasmosis in AIDS should be treated with an intensive primary
or induction therapy followed by lifelong suppressive or maintenance
therapy since complete eradication of the organism is impossible.
Amphotericin B is the antifungal agent of choice for induction
treatment. Itraconazole is preferred for the maintenance phase of
therapy. Nonmeningeal and nonseptic cases may be treated with
itraconazole in both the initial and chronic phases of treatment. In
situations where neither amphotericin B nor itraconazole may be
used (because of intolerance, reactions, or allergy), fluconazole is an
alternative option.
Prognosis
Prognosis is variable and hard to generalize. Disseminated
histoplasmosis, if untreated, especially in immunocompromised
patients, will lead invariably to death.
Prevention
&
Control
REFERENCES
Ajello L: Distribution of Histoplasma
2001
McGraw-Hill
71
Blastomyces
dermatitidis
Zelalem Temesgen MD
Essentials
of
Diagnosis
on
histopathological
examination.
General
Considerations
Epidemiology. Blastomyces
dermatitidis is an endemic
fungus that causes acute and chronic infections in humans
infection.
Microbiology. B dermatitidis is a dimorphic fungus, which
means that it occurs as a mold in nature and in a yeast form
in tissue (and at a temperature of 37C). The yeast cells
are round and thick walled with daughter cells forming from
a broad-based bud.
Pathogenesis. The lungs are the initial portal of entry for
blastomycosis in humans, although primary cutaneous
blastomycosis as a result of accidental skin inoculation in
the laboratory or after dog bites has been reported.
Infection begins with inhalation of conidia of the mycelial
phase of the organism. In the lungs, the fungus converts to
its yeast phase. Inflammatory response occurs in the form
of polymorphonuclear leukocyte infiltration followed by
macrophage infiltration and granuloma formation. The
infection can spread via the bloodstream and lymphatic
system to distant sites. Cellular immunity is the major
protecting factor in preventing progression of disease in
blastomycosis.
CLINICAL
SYNDROMES
1) .
PULMONARY
INFECTION
1.
ACUTE
Clinical
PULMONARY
INFECTION
Findings
More
Less
Common
Common
Uncommon
2.
CHRONIC
Pulmonary
Cutaneous
Skeletal
Genitourinary
Central nervous
Disseminated
PULMONARY
system
INFECTION
Clinical
Findings
EXTRAPULMONARY
INFECTION
1.
CUTANEOUS
BLASTOMYCOSIS
2.
SKELETAL
BLASTOMYCOSIS
3.
GENITOURINARY
BLASTOMYCOSIS
4. BLASTOMYCOSIS
NERVOUS
SYSTEM
OF
THE
CENTRAL
BLASTOMYCOSIS
&
AIDS
BLASTOMYCOSIS IN OTHER
IMMUNOCOMPROMISED
HOSTS
Blastomycosis has been reported to cause infection in other
Diagnosis
Blastomycosis is diagnosed by identification and isolation of the
organism in tissue, exudate, or histopathologic sections.
Direct
Examination. Sputum, pus, and body fluids such as
urine, pleural fluid, or cerebrospinal fluid can be evaluated
by direct microscopic examination. Wet preparation,
potassium hydroxide preparation, or calcofluor white stain
can be used for this purpose. B dermatitidis is recognized
and identified on the basis of its size and characteristic
morphologic features (broad-based buds, refractile cell
wall).
Histopathologic
Examination. Histopathologic sections
should be screened for presence of the fungus by using the
Gomori methenamine silver stain or the periodic acid-Schiff
stain. Fluorescent stains may be helpful when the fungal
elements are sparse. Pyogranulomas, if noted, suggest the
possibility of blastomycosis.
Culture. B dermatitidis usually requires 5 days to 4 weeks
for growth to be detected but may be detected in as little as
23 days. Conversion of the mycelial form to the yeast
test.
Treatment
Acute pulmonary infection caused by B
dermatitidis sometimes
Life-Threatening
Infection, Central
Nervous System
Infection,
First
Choice
Second
Choice
1 Patients
AIDS1
All others
Amphotericin B;
daily dose:
0.30.6 mg/kg
(total dose:
Itraconazole,
200400 mg
PO daily for a
minimum of 6
1.52.5
mg/kg)
mo
Itraconazole,
200400 mg
PO daily for a
Amphotericin;
daily dose:
0.30.6 mg/kg
minimum of 6
m o2
Ketoconazole,
400800 mg
(total dose:
1.52.5
mg/kg)
Ketoconazole;
daily for a
minimum of 6
mo
Fluconazole,
400800 mg
daily for a
minimum of 6
mo
200400 mg
daily for a
minimum of 6
m o3
Fluconazole;
200400 mg
daily for a
minimum of 6
mo
patients
with
osteomyelitis
refractory
to
pharmacotherapy.
Prognosis
The mortality rate for blastomycosis in HIV-infected patients is
much higher than the mortality rate from blastomycosis in the
general population. In one report, of 24 patients with HIV and
blastomycosis, 15 (63%) had disseminated disease, and 13
(54%) died
P.730
as a result of their infection. Previous reports have suggested a
mortality rate of ~ 10% in those with disseminated
blastomycosis but without concomitant HIV infection.
Precautions
Prophylaxis
1 The
Prevention
&
Control
REFERENCES
Baumgardner DJ et al: Epidemiology of blastomycosis in a
region of high endemicity in north central Wisconsin. Clin Inf
Dis
1992;15:62935.
Bradsher RW: Blastomycosis. Clin Inf Dis 1992;14(Suppl
1):S82S90.
Bradsher RW: A clinician's view of blastomycosis. Curr Top
Med
Mycol
1993;5:181200.
Rev
1995;8:14659.
2001
McGraw-Hill
72
Coccidioides
Caroline Milne MD
Merle Sande MD
Essentials
of
Diagnosis
General
Considerations
100,000
infections
occur
annually.
Clinicial
Findings
Table
Symptom
Frequency(%)
Cough
89
Fever
82
Chest pain
70
Headache
74
Shortness of breath
63
Malaise
59
Myalgias
52
Rash
52
1 Source:
Werner
1972.
and
antigen).
available.
C immitis readily grows in the laboratory and is detectable
as early as 25 days after inoculation. The fungal growth
is further evaluated via a species-specific DNA probe.
Results are available the day growth is detected. It is
important to notify the laboratory of your suspicions,
because laboratory identification may be dangerous to the
lab technician. Arthrospores readily become airborne and
may be inhaled.
There are two coccidioidal antigens that are targeted for
antibody detection, the tube precipitin reading (TP) antigen
and the CF antigen. Antibody detection kits are not
available, and instead laboratories use immunodiffusion
tests. Both tests are reported qualitatively; if
immunodiffusion CF is positive, a follow-up quantitative test
is necessary. The concentration of CF antibodies is
proportional to the extent of the disease. Ordering
physicians must be aware of false-negative results in
detecting
anticoccidioidal
P.733
Children
More
Common
Adults
Mild upper
respiratory
infection
Mild upper
respiratory
infection
Subacute, selflimited
pneumonia
Self-limited
pneumonia
Less
Complicated
Complicated
Common
pulmonary
infection
Extrapulmonary
disease
pulmonary
infection
Extrapulmonary
disease
Site
Primary
Alternative
Pulmonary and
Extrapulmonary
Fluconazole,
400800 mg
Itraconazole 200
mg orally twice
orally daily
(duration
1218
months)
a day (duration
1218
months) O R
Amphotericin B
0.61.0
mg/kg/d IV 7
d then 0.8
mg/kg/day total
dose 2.5 gms or
more)
Fluconazole
400600 mg
Amphotericin B
IV as above and
Meningitis
orally daily
indefinitely.
intrathecal
0.10.3 md
daily
Site/Indications
Treatment
Amphotericin B is used as
initial drug of choice
progressive
pulmonary
disease
Immunosuppressed
patients
because of rapid
improvement in
symptoms, followed
oral azoles.
HIV-infected
patients
Pregnant patients
Amphotericin B:
mg/kg/day for 7
then 0.8 mg/kg/
other day. Total
by
0.61.0
days,
every
dose 2.5
g.
Oral azoles: Itraconazole
200 mg twice a day O R
fluconazole 400 mg/day
for 312 months.
Disseminated
Differential
disease
Amphotericin B, 0.50.7
mg/kg/day. Total dose,
usually 1545 mg/kg.
Total dose not clearly
defined.
Diagnosis
differential.
Complications
Most
coccidioidal
infections
are
self-resolved.
Pulmonary
Treatment
In most cases the decision to treat is the real question. Recall
that even for patients who develop symptoms of initial infection,
the disease is usually self-limited. In patients in whom
treatment is indicated, coccidioidomycosis is very difficult to
cure. Treatment for initial infection is indicated only for patients
with deficiencies in T-cell immunity. A physician may decide to
treat a severe pulmonary infection, but there is no expert
consensus. Treatment is indicated for chronic pulmonary
infection and extrapulmonary dissemination. Accepted-standardof-care therapies include amphotericin B and oral azole
antifungal agents (Boxes 72-2 and 72-3). Fluconazole and
itraconazole have been shown to have similar success rates.
Length of treatment is controversial, because relapse is
common. Treatment may be lifelong. Most physicians will treat
pulmonary and disseminated disease for 1218 months. It has
been found that negative serial coccidioidin skin tests and very
high CF antibody titers are independently associated with
increased risk of relapse. Rising CF titers after completion of
therapy are an indication of relapse and warrant retreatment.
Patients with meningitis are likely never cured and require
indefinite treatment. Only fluconazole and amphotericin B have
been shown to be effective therapies. If amphotericin B is used,
both parenteral and intrathecal therapy is indicated.
Prevention
There is no vaccine available against C immitis infection.
General prevention includes avoiding exposure to the fungus in
its natural setting and decreasing the amount of airborne dust.
Environmental measures including paving dirt roads and
planting grass may be implemented (see Kirkland and Fierer,
1996) .
REFERENCES
Deresinski SC: History of coccidioidomycosis: dust to
dust. In Stevens DA, ed: Coccidioidomycosis. Plenum,
1980.
Diaz M A: Pan-American 5 year study of fluconazole therapy
for deep mycoses in the immunocompetent host. PanAmerican Study Group. Clin Infect Dis 1992;14(Suppl
1):S68.
Drutz DJ: Coccidioidomycosis, Part II. Am Rev Resp Dis
1978;117:727.
Feigin R, Cherry J (editors): Textbook
Diseases, 4th ed. Saunders, 1998.
of
Pediatric
Infectious
2001
McGraw-Hill
73
Candida species
Christopher R. Fox MD
Merle A. Sande MD
Essentials
of
Diagnosis
General
Considerations
CLINICAL
SYNDROMES
CANDIDA
DERMATITIS
Clinical
Findings
Signs and Symptoms. Skin infections with Candida are common and
may manifest in a variety of forms. Intertrigo occurs in warm, moist
areas of skin, such as under the breast, in the groin, and in the axilla.
Initially pustular or vesicular, lesions eventually become confluent to
form an erythematous, macerated area of skin with a scalloped border
and satellite lesions (Box 73-1 ). Erosio interdigitalis blastomycetica is
similar to intertrigo but involves the areas between the fingers and
toes. Paronychia is infection of the nail bed, seen more commonly in
diabetics and people who frequently immerse their hands in water.
Candida spp. may cause onychomycosis, particularly in HIV-infected
patients. Candida spp. cause a rash in neonates in the region of diaper
contact. Other common skin manifestations include folliculitis,
balanitis, perianal candidiasis, and a generalized cutaneous eruption
with widespread lesions resembling intertrigo that spread to involve the
abdomen, chest, back, and extremities.
Chronic mucocutaneous candidiasis (CMC) is an abnormality of cellmediated immunity that presents with recurrent infections of the skin
and mucus membranes that may progress to disfiguring lesions
(Candida granulomas) despite antifungal therapy. Symptoms usually
begin in the first several years of life. CMC is associated with
autoimmune endocrine failure, particularly hypoparathyroidism and
adrenal insufficiency (polyglandular autoimmune syndrome type I), and
endocrine disease often presents years to decades after the onset of
CMC.
Cutaneous lesions may be superficial evidence of disseminated
candidiasis and candidemia. Lesions are typically red or pink nodules
510 mm in diameter and may be single or widespread. Lesions
resembling ecthyma gangrenosum or purpura fulminans have also been
described.
Laboratory
Findings. Candida organisms, seen as budding yeast and
hyphae, may be present on wet mount or KOH preparations of skin
scrapings. Biopsy specimens may reveal characteristic fungal elements
on histology.
Differential
Diagnosis. Candida infection of the skin and nails may be
confused with other infections, both fungal and nonfungal, as well as
noninfectious conditions such as contact or allergic dermatitis.
Complications. Candida infection of the skin and nails may cause
discomfort and disturb cosmetic appearance of the skin but does not
usually cause long-term sequelae. CMC may progress to cause large
disfiguring
lesions.
Diagnosis
Diagnosis of Candida infection involving the skin or nails is generally made
by recognition of the clinical pattern followed by demonstration of fungal
elements on a KOH preparation of skin scrapings. Candida infection may
also be diagnosed by microscopic examination of biopsy specimens. Culture
of the skin should be interpreted with caution, as the presence of Candida
spp. may represent colonization rather than infection.
Treatment
Treatment of Candida skin infections is generally straightforward.
Intertrigo is managed by decreasing moisture in infected areas and by
application of topical antifungal therapy. Nystatin cream, topical azoles
(miconazole, clotrimazole), and amphotericin B cream are all effective
when applied 23 times daily. Paronychia may be treated by keeping the
area dry and with topical antifungal therapy. Onychomycosis requires
several months of treatment with oral azoles, such as itraconazole, or
terbenifine. Relapses may occur. Griseofulvin is not active against Candida.
.
CMC is treated with oral ketoconazole or fluconazole. Transfer factor, an
immunomodulating factor composed of a cell-free leukocyte extract, was
used in the past but has fallen out of favor because of lack of efficacy.
Months to years of treatment are generally required.
ORAL
Clinical
CANDIDIASIS
Findings
More
Common
thrush
Common
Perforation
Diffuse involvement of stomach similar to thrush
Deep ulceration
Hemorrhage
Perforation
Dermatitis
Oral
Esophageal
GI
(Nonesophageal)
Vulvovaginal
Diagnosis
The diagnosis of oral Candida infection may be suspected when the
characteristic appearance of the mucosa is present and, in the case of oral
thrush, when scraping of the mucosa removes the white plaque and leaves
an inflamed mucosa. Demonstration of dimorphic fungi on KOH-, Giemsa-,
Gram-, or PAS-stained oral scrapings strongly supports the diagnosis.
Culture of Candida species from oral scrapings is not generally required,
and as Candida may be part of the normal flora of the oral cavity, positive
cultures may not represent true infection.
More
Common
Asymptomatic
Patient with risk factors 1
Patient with risk factors 2
Presentation ranges from asymptomatic to septic shock
Positive blood cultures
Microabscesses involving multiple organs
Patient with risk factors 3
Fever, malaise, weight loss
Embolic phenomena
Less
Common
perforation
Candidemia
and
Disseminated
Candidiasis
Endocarditis
Treatment
Generally, oral Candida infection should initially be treated with topical
agents (Box 73-3 ). Nystatin suspension or clotrimazole troches are
generally effective therapy. If infection occurs in a denture wearer, the
dentures must be removed. Once the infection is cured, proper dental
hygiene is important to prevent recurrence. Topical antifungal creams will
treat angular cheilitis.
If topical therapy fails, or in those with severe infection, systemic therapy
may be used. In patients with advanced HIV infection, itraconazole doses
may require adjustment because of achlorhydria and impaired absorption.
Treatment failure should prompt a search for other causes, such as
bacterial infection or malignancy.
In those infected with HIV or with other immune deficits, frequent
recurrences are common, and maintenance therapy may be necessary.
ESOPHAGEAL
Clinical
CANDIDIASIS
Findings
Diagnosis
Radiographic techniques using barium contrast (barium swallow) and
endoscopy are useful for diagnosis of Candida esophagitis. The barium
swallow has a characteristic appearance, with a shaggy-appearing mucosa
and sometimes nodules and cobble stoning. This technique does not allow
firm diagnosis, which requires histology or culture.
Endoscopy is the preferred method of diagnosis, as it allows direct
visualization of the mucosa and biopsy of affected areas. The mucosa
typically has adherent white plaques that may be removed with the
endoscope to reveal an erythematous mucosa. Brushings of the mucosa
may be prepared as for oral disease. Histologic specimens reveal fungal
elements, which are more apparent on PAS-stained and silver-stained
material than with hematoxylin-eosin staining.
Treatment
A subset of patients may be treated empirically. In those with HIV
infection, oral thrush, and mild to moderate symptoms of esophagitis,
treatment with topical agents or an azole may be warranted. If no oral
thrush is present, or if treatment fails, endoscopy should be performed to
exclude other causes of disease.
CANDIDA
Clinical
VULVOVAGINITIS
Findings
Signs and Symptoms. Risk factors for Candida infection of the vagina
include pregnancy, oral contraceptive use, diabetes mellitus, HIV
infection, and antimicrobial therapy, although the majority of infections
occur in the absence of these risks. Typical complaints are vulvar
pruritus and vaginal discharge (Box 73-1 ), although a wide range of
symptoms exists. Pruritus, the most common complaint, is often
intense,
P.739
and the discharge, classically described as cottage cheeselike, may
range from a thin, white, scant discharge to homogeneously thick.
Odor, if present, is mild. Other symptoms may include vulvar burning,
external dysuria, vaginal irritation and soreness, and dyspareunia.
Symptoms may peak the week prior to menses and wane with the
onset of menstrual flow.
Examination may reveal discrete papular or pustular lesions of the
vulva, with erythema and swelling of the vulva and labia. The discharge
is present within the vaginal vault, and the vaginal mucosa is inflamed
and may have adherent white plaques similar to oral thrush. The cervix
appears normal.
Laboratory
Findings. The vaginal pH is normal (<4.5). Examination of
a saline or wet mount preparation of the vaginal discharge may show
fungal elements and should not reveal abundant white cells. A KOH
preparation is more sensitive in detecting the fungus, as other cellular
debris is lysed. Both budding yeast and hyphae are typically present.
Culture of the vagina will usually isolate Candida , although this must
be interpreted cautiously, as Candida can be part of the vaginal flora
without
causing
disease.
Differential
Diagnosis. The signs and symptoms of Candida
vulvovaginitis are relatively nonspecific, and therefore the presentation
may be confused with bacterial vaginosis, trichomoniasis, and other
sexually transmitted diseases. Two or more of these conditions may
coexist.
Complications. Some women may develop severe, recurrent infections
despite removal of identified risk factors and antifungal therapy.
Infection of the vagina is not associated with risk of deep tissue or
bloodstream
invasion.
Topical
Nystatin suspension (100, 000 units/mL) 1030 mL 45 times daily
Clotrimazole troches (10 mg) 5 times daily
Systemic
Fluconazole 50200 mg PO every day 10 days
Itraconazole1 50200 mg PO every day 10 days
Amphotericin B 0.30.6 mg/kg/day IV 10 days
1
Esophagitis
Diagnosis
The diagnosis of vulvovaginitis is typically made by history, physical
examination, and light microscopy. In women with appropriate symptoms
and fungal elements on wet mount or KOH preparation, therapy is indicated
without further testing. As up to 50% of symptomatic women with cultureproven infection have negative microscopy, vaginal culture is indicated in
those patients with symptoms and no microscopic findings. A vaginal pH
>4.5 or a large number of white cells on wet mount should prompt a
search for a different or possibly coexistent process.
Treatment
Numerous agents are available for treatment of Candida vulvovaginitis in
both topical and oral preparations (Box 73-5 ). Among topical agents, cure
rates range from 75 to 90%, with the azole preparations (clotrimazole,
miconazole, terconazole) having slightly better efficacy than nystatin. The
formulation (cream versus suppository versus vaginal tablet) does not alter
the success rate; therefore the choice of formulation is a matter of patient
preference. Currently there is a trend toward higher doses of topical agents
with shorter durations of therapy, with success reported with even highdose, one-time therapy. Anecdotal failure rates are fairly high with onedose therapy; thus this is best reserved for women with infrequent
infections and mild or moderate symptoms.
Topical
Butoconazole, 2% cream, 5 g every day 3 d
Clotrimazole,
Clotrimazole,
Clotrimazole,
Clotrimazole,
1% cream, 5
vaginal tablet,
vaginal tablet,
vaginal tablet,
Vulvovaginitis1
Oral azole agents are quite effective for vaginal infection and are more
convenient than topical therapy but are more expensive. Fluconazole and
itraconazole single-dose therapy are at least as effective as topical
therapy.
Cure of Candida vulvovaginitis during pregnancy can be difficult, with
relapses frequently occurring. If
P.740
therapy is extended to 12 weeks, topical antifungal therapy is effective.
Oral azoles should be avoided during pregnancy.
In women with frequent recurrent infections, therapy is often
disappointing, with symptoms recurring within weeks of withdrawal of
antifungal agents. In these women, predisposing factors such as diabetes
or HIV infection should be considered. HIV testing is appropriate in women
with risk factors for HIV infection. If fasting blood glucose values are
normal, further testing for diabetes is not required. Oral contraceptives
should be discontinued if possible, although continuation of low-dose
estrogen preparations, as long as long-term antifungal therapy is used,
may be considered. Vaginal douching and treatment of the sexual partner
are not recommended. Frequently, no risk factors are identified, and
prophylactic therapy is required. The best-studied regimen with proven
efficacy for prophylaxis is ketoconazole, 100 mg daily. Toxicity, such as
hepatitis, is infrequent but may occur. Other regimens with anecdotal
support include fluconazole, 100200 mg once weekly, and clotrimazole
vaginal tablets, 500 mg once weekly.
Diagnosis
Candiduria is usually discovered when a urine culture reveals the presence
of Candida spp. The presence of pyuria generally indicates true infection if
other etiologies, such as bacterial infection, have been excluded. Infection
may also be diagnosed by demonstrating the presence of a typical
appearing fungus in biopsy specimens obtained during cystoscopy.
Of particular importance for treatment is whether candiduria represents
colonization or true infection, and whether the upper urinary tract is
involved, a distinction that can be troublesome. Those with risk factors for
ascending infection (diabetes, stones) and those at risk for disseminated
disease are more likely to have upper urinary tract infection. Computerized
tomographic scans or ultrasound may reveal microabscesses or fungus
balls.
Treatment
When treating Candida infection of the urinary tract, careful consideration
must be given to whether candiduria represents colonization or true
infection, and whether the upper urinary tract is involved. Asymptomatic
candiduria usually does not require antifungal treatment, but indwelling
CANDIDEMIA &
CANDIDIASIS
DISSEMINATED
Candiduria
Diagnosis
Candidemia is diagnosed by recovering Candida species in blood culture.
Candidemia may be isolated or may occur in the setting of disseminated
candidiasis. The possibility of disseminated candidiasis should be
considered in any patient with deep Candida infection, multiple sites of
infection, or positive blood cultures. Disseminated candidiasis is diagnosed
by tissue culture of biopsy material or demonstration of Candida in
histologic specimens. At present, serology is available but has falsenegative and false-positive rates too high to be of use clinically.
Treatment
The treatment of candidemia is the subject of much debate and
controversy. Because isolation of Candida from the blood carries a high
morbidity and because there is currently no method to predict which
patients will not require treatment, there is agreement that all patients
with candidemia should be treated. The standard treatment in the past has
been amphotericin B, with or without 5-FC. Currently, fluconazole appears
to be a reasonable alternative, although
mortality of fluconazole-treated patients
amphotericin. One randomized study of
fluconazole to be equally efficacious but
compared
with
amphotericin.
Choice
B,
0.81.0
Children
CANDIDA
ENDOCARDITIS
mitral valves are commonly infected. The symptoms are similar to that of
bacterial endocarditis with fever, malaise, weight loss, and signs and
symptoms of embolic phenomena. Splinter hemorrhages, Osler's nodes,
Janeway lesions, hepatosplenomegaly, hematuria, proteinuria, and pyuria
may all occur. Candida has the ability to cause large vegetations and large
emboli, which may be catastrophic, and valvular lesions may progress to
cause perforation, congestive heart failure, and myocarditis (Box 73-2 ).
Diagnosis
Blood cultures are generally positive in Candida endocarditis, although
negative cultures may occur in up to 25% of patients. Echocardiography
reveals vegetations, which may become quite large. Transesophageal
echocardiography is more sensitive for detection of vegetations than
transthoracic echocardiography. The role of serologic tests (Candida
antibodies) is uncertain, as both false positive and false negative results
occur with some frequency.
Treatment
Treatment of Candida endocarditis generally requires combined surgical
and medical therapy. Once the diagnosis is established, therapy with
amphotericin B should be initiated and the valve replaced as soon as
possible (Box 73-8 ). Antifungal therapy is generally required for a total of
610 weeks, and patients should be monitored for a minimum of 2 years
after completion of therapy because of the high risk of relapse. For those
in whom surgical treatment is not possible, such as those too ill to survive
an operation, there exist case reports of treatment success with medical
therapy alone (amphotericin B followed by fluconazole).
GI
CANDIDIASIS
(NONESOPHAGEAL)
Candida species may infect any mucosal surface of the GI tract. After
esophageal candidiasis, infection of the stomach is most common.
Typically, the organism is seen infecting benign ulcers, although a diffuse
mucosal form of infection resembling thrush has been described. In the
small and large bowel, ulceration and pseudomembrane formation are
common. Mucosal GI involvement may cause deep ulcerations with
Diagnosis
Involvement of nonesophageal mucosal involvement of the GI tract is
generally diagnosed by characteristic appearance during endoscopy and by
demonstration of Candida by histology or culture of biopsy
P.743
specimens. Involvement of the peritoneum, liver, spleen, gallbladder, and
pancreas may be difficult to diagnose. Fluid returned after peritoneal
dialysis may grow Candida in culture. Computer tomography or magnetic
resonance imaging may reveal splenic or hepatic abscesses. Laparoscopy
may be required for definitive diagnosis.
Endocarditis
Treatment
Fluconazole is recommended for initial therapy of mucosal involvement in
the stomach, small intestine, or colon (Box 73-9 ). Amphotericin B may
also be used. Candida peritonitis may also be treated with fluconazole
alone or amphotericin B followed by fluconazole. Peritoneal dialysis
catheters should be removed if possible. For patients with a perforated
OTHER CANDIDA
SYNDROMES
Spleen,
Gallbladder,
Peritoneum
Diagnosis
The diagnosis of Candida infection of the lung, CNS, musculoskeletal
system, or eye generally requires demonstration of the organism by tissue
culture or on histologic examination. However, visualization of the typical
well-demarcated white retinal or vitreal lesion by funduscopic examination
in the setting of positive blood cultures is adequate for the diagnosis of
Candida endophthalmitis. It should be noted that sputum culture is
generally not sufficient for diagnosis of respiratory involvement,
particularly in an intubated patient, as the organism may only be colonizing
the respiratory tract.
Treatment
Amphotericin B has been the standard treatment for Candida infection in
the CNS, eye, lung, and musculoskeletal system. Prosthetic material or
other foreign bodies should be removed, if possible. The role of 5-FC is not
clear, but it may be added to amphotericin. There is growing support for
the use of the azole class, particularly fluconazole, as treatment for deep
Candida infection. While case reports of success with fluconazole exist,
there are very limited data regarding fluconazole in these settings and
virtually no data comparing fluconazole with amphotericin.
Prevention
&
Control
of C a n d i d a
Infections
Measures
Precautions
Generally
not
required
REFERENCES
Cormican MG, Pfaller MA: Epidemiology of candidiasis. Comp Ther
1995;21:653.
Edwards JE Jr: Candida species. In Mandell GL, Bennett JE, Dolin R:
Principals and Practice of Infectious Diseases, 4th ed. Churchill
Livingstone, 1995.
Edwards JE Jr et al: International conference for the development of a
consensus on the management and prevention of severe candidal
2001
McGraw-Hill
74
Cryptococcus
neoformans
James J. Chamberlain MD
Donald L. Granger MD
Essentials
of
Diagnosis
General
Considerations
canaries.
The variant gattii has been isolated most frequently from
tropical and subtropical climates, most commonly in Australia,
Southeast Asia, Brazil, Venezuela, Zaire, and southern
California. This finding appears to be related to the
distribution of the river red gum tree (Eucalyptus
camaldulensis), which harbors the organism. Infectivity
correlates with flowering of eucalyptus trees. The organism
does not cause outbreaks or clusters of infection, and a lack
of history of exposure to bird droppings or flowering
Eucalyptus trees should not exclude the diagnosis of
Cryptococcus
infectionor
cryptococcosis..
AIDS and the use of immunosuppressive drug therapy have
produced a dramatic rise in the number of infections due to C
neoformans over the past 25 years (see Chapter 40). In fact,
more cases of cryptococcosis were described in the United
States in 1976 (338 cases) than had been described worldwide
by 1955 (~ 300 cases). Prior to the AIDS epidemic, nearly
Table
Characteristic
Variety gattii
Geographic
distribution
Worldwide
Tropical
and
subtropical
regions
Reservoir
Pigeon
Eucalyptus
trees
Host
predisposition
AIDS
Sarcoid
Mostly
normal
Lymphoma
Corticosteroids
CLL, ALL
Organ
transplantation
hosts
Infection
AIDS
in
C neoformans grows
agar, a characteristic
other
nonpathogenic
usually visible within
smooth colonies.
The
Variety
neoformans
Yes
feces
Rare
Clinical
Findings
95% of AIDS
will have positive
identification of
ink preparation occurs
Treatment
The treatment of patients with cryptococcosis is determined by
whether they are HIV positive or negative and whether they have
localized pulmonary or disseminated (usually meningitis)
involvement.
HIV-negative
patients. For mild to moderate pulmonary
infection without evidence of dissemination, oral fluconazole
for 612 months is adequate (Box 74-1). In meningitis,
cryptococcemia, or severe pulmonary infection, preferred
treatment includes a combination of amphotericin B plus 5flucytosine for 2 weeks followed by oral fluconazole daily for a
minimum of 10 weeks (Box 74-1). 5-Flucytosine is given every
6 h. Serum levels should be monitored and the dose adjusted
to give 2040 g/ml peak concentrations. Complete blood
counts are required to detect toxicity and should be done
Mild to Moderate
Pulmonary Disease
First
Choice
Second
Choice
CNS or Severe
Pulmonary Disease
Fluconazole,
200400 mg/d
for 612
Amphotericin B,
0.71.0 mg/kg/d
for 2 weeks; then
months
fluconazole, 400
mg/d for a
minimum of 10
weeks
Amphotericin B,
0.51.0
mg/kg/d (total,
10002000
mg0)
Amphotericin B,
0.71.0 mg/kg/d
plus 5 flucytosine,
100 mg/kg/d for
610 weeks
First
Choice
Mild to
Moderate
Pulmonary
Disease
Body Sites
Fluconazole,
200400
mg/d (for
life)
Induction/consolidation:
Amphotericin B,
0.71.0 mg/kg/d plus
5-flucytosine, 100
mg/kg/d for 2 weeks;
then fluconazole, 400
mg/d for minimum of
10 weeks
Maintenance:
Fluconazole,
200400
mg PO daily for life
Second
Choice
Fluconazole,
400 mg/d
Induction/consolidation:
Amphotericin B,
plus
flucytosine,
100
mg/kg/d for
10 weeks
Prognosis
Cure of CNS cryptococcosis in AIDS patients is rare.
Consequently, management is aimed at long-term suppression
therapy. The effect of HAART on ability to cure cryptococcosis is
unknown. Close follow-up throughout the course of initial therapy
and maintenance therapy is imperative in AIDS-associated CNS
Prevention
&
Control
REFERENCES
Baughman RP et al: Detection of cryptococcal antigen in
bronchoalveolar lavage fluid: a prospective study of diagnostic
utility. Am Rev Respir Dis 1992;145:1226.
Cameron ML et al: Manifestations of pulmonary cryptococcosis
in patients with acquired immunodeficiency syndrome. Rev
Infect Dis 1991;13:64.
2001
McGraw-Hill
75
Aspergillus, Pseudallescheria,
Mucormycosis
&
Agent
Michael R. Keating MD
ASPERGILLUS
Essentials
of
INFECTION
Diagnosis
General
Considerations
Aspergillus
conidia or spores in the home, office, or hospital setting. Th
are extremely heat resistant and can withstand extreme environmental
the status of the host defenses. The pulmonary macrophage is the first l
against inhaled conidia. Macrophage function may be rendered ineffective
corticosteroid therapy or other immunomodulating chemotherapy. The tis
also pivotal. Altered phagocytosis or cellular killing by the neutrophil ma
mellitus.
P.752
composed of exuberant filamentous growth of Aspergillus spp. The cavit
is lined by vascular granulation tissue, while the cavity itself contains h
inflammatory cells, amorphous debris, and mucus. Superficial invasion of
may occur, but dissemination is rare unless the patient also has other ri
invasive disease. Erosion into adjacent pulmonary vessels may occur and
hemoptysis, which on occasion may be massive and result in death.
CLINICAL
SYNDROMES
1.
and
rapidly
INVASIVE
progressing
disseminated
PULMONARY
life-threatening
disease
ASPERGILLOSIS
Clinical
Findings
Laboratory
Findings. Hypoxemia is often present in patients with exte
involvement. Other laboratory abnormalities are nonspecific. Because of
immunodeficient state, serum antibodies to Aspergillus spp. are usually
P.753
people is occasionally seen so it may be difficult and a challenge to dist
Differential
Diagnosis. The differential diagnosis of a new infiltrative lu
immunosuppressed patient is very broad. Other fungi including Pseudalles
the order Mucorales can cause an identical syndrome. Nocardia lung infe
in presentation. Mycobacterial infection is less likely but must be consid
infection including that caused by Staphylococcus
aureus and Pseudomona
possible. Rhodococcus equi is a rare but emerging pathogen that present
especially if cavitation is present.
More
Common
Allergic
bronchopulmonary
Aspergilloma
aspergillosis
aspergillosis
Common
Osteomyelitis
Endocarditis
Endophthalmitis
Endophthalmitis
Osteomyelitis
Disk space infection
Endocarditis
Otomycosis
Aspergillus tracheobronchitis
Children
Adults
Diagnosis
risk patient and imaging evidence consistent with Aspergillus infection should
presumptive invasive pulmonary aspergillosis and justification for empiric an
patients with negative cultures or in whom sputum cultures cannot be obta
Treatment
an oral azole with activity against Aspergillus spp. Its use should be reserve
are not severely immunosuppressed, who have an indolent or chronic infectio
intolerant of amphotericin B therapy. The optimal duration of antifungal thera
but the cumulative total dose is 2 g of amphotericin B. In patients with
pulmonary infection, resection should be considered.
(200,
methenamine
silver
stain).
Prognosis
Prevention
&
Control
No
Amphotericin B
No
No
No
1.01.5 mg/kg/d IV (23 g total target dose) in adults; 3035 mg/kg
children
11.5 mg/kg, if needed (23 g total target dose) in adults; 3035 mg
children
Intraconazole
No
Investigational
No
400 mg PO once daily as secondline option for indolent case or after IV amp
induction therapy; itraconazole dose for children, 56 mg/kg/d
No
Surgery
No
No
In selected cases
An option for localized disease
Surgical dbridement; surgical excision and drainage may be adequate
Invasiv
Pulmona
Aspergill
Treatment
Option
Farmer's
Lung
Allergic
Bronchopulmonary
Aspergillosis
Aspergilloma
and
Dissemina
Asperillo
P.754
Reducing exposure to at-risk hospitalized patients can be achieved in severa
plants should be removed from the environment adjacent to at-risk patients
such as cereal and spices, have been found to be contaminated with Aspergi
should not be offered to hospitalized patients that are at risk for aspergillos
and adjacent to hospitals has been associated with outbreaks of nosocomial
Patients should not be treated in areas of the hospital where construction or
occurring. If a patient must be transported through areas of construction wit
efficient mask should be worn by the patient. Efforts should be made to sea
construction or remodeling to prevent contamination of the air in patient are
HEPA filtration of air has been shown to significantly reduce or eliminate Asp
Patient rooms with laminar airflow and HEPA filtration appear to be effective
risk of exposure in the hospital. Unfortunately, the construction and mainten
filtered facilities are very expensive and not available to all patients. Other
been used include high air exchange rates, surveillance air sampling, positive
patient's room and immediate environment, and regular filter changing of p
filtration systems.
Reduction
of
environmental
exposure
antifungal
therapy
Amphotericin B, 1 mg/kg/d IV
Amphotericin B, 0.10.15 mg/kg/d
Lipid preparations of amphotericin B
Oral itraconazole, 200400 mg/d; for children 36 mg/kg/d
Intranasal or aerosolized amphotericin B
Too toxic to be used prophylactically
Usually can be tolerated but dose may be too low to be effective
No clinical data; prohibitive cost
Limited clinical data; unpredictable absorption
Promising approach; more data needed
Strategy
Goal or Limitations
P.755
The use of intravenous amphotericin B for prophylaxis against Aspergillus sp
investigated. When given prophylactically at a dose of 1 mg/kg/d, the toxici
high. When used prophylactically at lower doses of 0.10.25 mg/kg/d, the
in most studies, this dosage was insufficient to prevent aspergillosis. The lip
amphotericin B are attractive for prophylaxis alternatives; however, the high
preparations limit their widespread use.
Among the oral azoles, only itraconazole has sufficient activity against Asper
considered as a viable prophylactic agent. There are limited data confirming
preventing aspergillosis in high-risk patients. Moreover, the absorption of itr
2.
ASPERGILLOMA
An aspergilloma of
disease caused by
known as a fungus
colonization of the
Clinical
Findings
Laboratory
Findings. Patients with an aspergilloma of the lung typicall
levels specific for Aspergillus spp. Sputum smear may show the presenc
fungi, and culture is intermittently positive for Aspergillus spp.
Imaging. The chest x-ray will show typical findings of a fungus ball with
sign. Both CT and magnetic resonance imaging (MRI) of the chest reveal
(see Figure 75-2 ).
Differential
Diagnosis. In a patient with a history of prior lung diseas
lead to the suspicion of a fungus ball. Other fungi including Pseudallesche
cause a similar syndrome. Other causes of hemoptysis including tubercu
embolism, lung cancer, and bronchiectasis need to be considered.
Diagnosis
Treatment
Treatment for aspergilloma must be individualized
P.756
(see Box 75-2 ). For patients with mild hemoptysis, observation alone is wa
with more significant hemoptysis may benefit from lobectomy, but preexistin
place the patient at increased risk for surgical complications. There is no rol
antifungal therapy. No consistent benefit has been derived from intracavitary
amphotericin
B.
Prognosis
Most patients with mild stable hemoptysis do very well. In some patients, th
gradually enlarge, and close observation of these patients is warranted.
3.
DISSEMINATED
ASPERGILLOSIS
Clinical
Findings
Laboratory
Findings. Despite hematogenous route of dissemination, bl
rarely positive. Urine cultures may be positive for Aspergillus cells when
Diagnosis
Treatment,
Prevention,
&
Control
4.
ALLERGIC
BRONCHOPULMONARY
ASPERGI
Clinical
Findings
Laboratory
Findings. Peripheral eosinophilia is a hallmark of allergic
aspergillosis and is usually > 1000 cells/mL. Other findings include eleva
levels, serum precipitans to Aspergillus
fumigatus , and immediate whea
to Aspergillus skin testing.
P.757
Culture of the sputum reveals large numbers of A fumigatus colonies. An
IgG and the IgE class that are specific for A fumigatus are elevated.
Differential
Diagnosis. Other common causes of eosinophilic pneumon
infestation and drug-induced lung disease. Allergic bronchopulmonary a
also be distinguished from a number of idiopathic eosinophilic pneumoni
Lffler's syndrome, chronic eosinophilic pneumonia, Churg-Strauss synd
hypereosinophilic
syndrome.
Diagnosis
fumigatus of the IgG and IgE class. Microscopic examination of sputum may
lancet-shaped crystals originating from the Charcot-Leyden crystal proteins f
cytoplasm of eosinophils.
Treatment
diagnostic
1 . Bronchial
2.
3.
4.
5.
criteria
asthma
Peripheral
eosinophilia
Immediate wheal and flare response to Aspergillus
Pulmonary infiltrates on chest x-ray
Serum precipitans to A fumigatus
fumigatus antigen
supportive
criteria
75-1.
Diagnostic
criteria
for
allergic
bronchopulmonary
asper
Prognosis
5.
FARMER'S
LUNG
disease (from mold on tobacco leaves), and malt worker's lung (from moldy
Clinical
Findings
Laboratory
Findings. Neutrophilia may be seen, but eosinophilia is typ
Aspergillus serum precipitans will be elevated in most cases, but their pr
Imaging. Chest x-ray findings may be normal even in patients with sig
Conversely, the chest x-ray may show diffuse bilateral pulmonary infiltra
nodular infiltrates. With more chronic symptoms, pulmonary function test
restrictive
pattern.
Differential
Diagnosis. Acute and subacute Farmer's lung will occasion
infectious pneumonitis. Farmer's lung must be distinguished from other
cause respiratory symptoms and pulmonary infiltrates, including collagen
eosinophilic pneumonitis, and drug-induced lung disease. In its more chr
resemble idiopathic pulmonary fibrosis and other interstitial lung disorde
P.758
with chronic exposure and ongoing allergic reaction may develop pulmon
restrictive pattern seen on pulmonary function testing.
Diagnosis
The diagnosis should be suspected from the history of exposure and the sym
Laboratory testing can help distinguish Aspergillus -induced Farmer's lung fr
Farmer's lung.
Treatment
Prognosis
Prevention
&
Control
6 . ASPERGILLUS
SINUSITIS
recurrent sinusitis. Facial pain and nasal discharge are predominant sym
syndrome.
Laboratory
Findings. Cultures of nasal secretions are usually positive
in patients with invasive and noninvasive forms of sinus infection.
orbit, the brain, or the roof of the mouth. No bony destruction occurs in
disease.
Differential
Diagnosis
Aspiration of sinus contents should be cultured and stained for fungal eleme
examination of the nose should be considered. High-resolution CT imaging c
and extent of involvement.
Treatment
P.759
Antifungal therapy with amphotericin B is illustrated in Box 75-2 . For nonin
including chronic sinusitis and sinus aspergilloma, surgical excision and drain
adequate, and systemic antifungal therapy is usually not needed.
Host
Immunocompetent
Immunosuppressed and
Tempo of Infection
Chronic and indolent
usually
profoundly
Invasive
sinusitis.
Prognosis
Prevention
&
Control
INFECTION
but can also occur in other immunosuppressed patients (Figure 75-3 ). Inva
may begin in the skin and disseminate to other sites. For example, focal inf
at intravenous catheter sites in neutropenic patients and cause progressive
before there is evidence of systemic dissemination.
PSEUDALLESCHERIA
Essentials
of
BOYDII
INFECTION
Diagnosis
General
Considerations
tissue, P boydii produces thin septate hyphae that are similar in appeara
hyphae. Hence it is not possible to distinguish P boydii infection from As
based on histopathology, and culture confirmation is necessary to establ
and guide therapy.
Clinical
Findings
P.760
trauma may result in soft tissue infection. It is the most common cause of
the United States. Infection involving the globe after penetrating trauma has
relatively frequently. A unique syndrome of P boydii in normal hosts is an o
pneumonia after near drowning and aspiration of fresh or brackish water. D
brain and other tissues has been reported in this setting.
infection, but soft tissue infection, central nervous system infection, and othe
seen.
Diagnosis
Treatment
First Choice
Miconazole, 800 g IV every 8 for children: 2040 mg/k in 3 divided dos
Second Choice
Itraconazole, 400 mg PO once daily; for children; 56 mg/kg/d
Role of Surgery
In selected cases
Comments
Amphotericin B resistant
BOX 75-4 Treatment of Pseudallescheriosis
MUCORMYCOSIS
Essentials
of
Diagnosis
General
Considerations
Cunninghamella. These fungi are relatively rapid growing and will grow o
the mycology laboratory in 25 days. They grow only as mold, and the
uneven in diameter and often quite large, ranging in size from 5 to 50
Branching occurs at irregular angles, in contrast to the 45 angles of b
P.761
skin. Alteration of macrophage and neutrophil function secondary to dia
and corticosteroids allows the initial sporulation and filamentous growth.
Figure 75-4. Culture specimen of Mucor sp., showing irregular hyphae with
fruiting body of Mucor sp. is also present ( 800, lactophenol cotton blue
CLINICAL
1.
SYNDROMES
RHINOCEREBRAL
MUCORMYCOSIS
Clinical
Findings
Laboratory
Findings. There are no typical laboratory abnormalities ass
condition except as noted above. The onset of symptoms may occur dur
phase of diabetic ketoacidosis. Most leukemic patients that develop this
while still profoundly neutropenic. Cultures of nasal secretions or biopsy
commonly negative even when hyphal elements are present.
Imaging. X-rays of the sinuses are generally insensitive but will demo
2.
PULMONARY
MUCORMYCOSIS
Laboratory
Findings. Hypoxemia may be present depending on the ext
involvement. Sputum cultures may grow an agent of mucormycosis or m
Differential
Diagnosis. Mucormycosis may simulate other opportunistic
involving the lung such as invasive pulmonary aspergillosis. At the onset
pulmonary mucormycosis can resemble pulmonary embolization caused b
dyspnea, hemoptysis, and pleuritic chest pain.
Most of the symptoms are caused by embolization from the large valvular v
form. Valve replacement surgery can be curative. Gastrointestinal mucormyc
patients with profound malnutrition. Involvement of multiple sites in the ga
seen. Abdominal pain and fever are the usual symptoms. Cutaneous mucorm
direct inoculation of the skin in patients with burns, diabetes mellitus, or tra
The skin may also be a sight of hematogenous dissemination. Hemodialysis
desferoxamine therapy for aluminum overload are at increased risk for any f
mucormycosis caused by Rhizopus spp.
Diagnosis
Figure 75-5. Large black necrotic ulceration on the thigh of a patient with
diabetes mellitus. This fatal infection began as a papule and enlarged over 4
Treatment
Once the diagnosis of mucormycosis has been established, the initial approa
should be to correct aggressively any predisposing factors (see Box 75-5 ).
diabetic ketoacidosis or hyperglycemia, metabolic abnormalities need to be
controlled. Patients receiving immunosuppressive therapy, especially cortico
have this reduced as much as possible. Antifungal therapy should be institut
amphotericin B. The duration of therapy should be based on clinical respons
azoles do not appear to be effective against the agents of mucormycosis. Th
with mucormycosis because of the high dose required and underlying patien
First Choice
Amphotericin B, 11.5 mg/kg/d IV
Second Choice
Lipid formulation ofamphotericin B
Role of Surgery
Dbridement required for rhinocerebral
Comments
form
Prognosis
Prevention
&
Control
REFERENCES
DeShazo RD, Chapin K, Swain RE: Fungal sinusitis. N Engl J Med 1997;33
of-the-art discussion of the spectrum of infection associated with fungal s
infections in patients with neoplastic diseases. Curr Opin Oncol 1992; 4(4
of the progress and challenges in the management of invasive fungal infec
patients.)
2001
McGraw-Hill
76
Sporothrix
schenckii
Zelalem Temesgen MD
Essentials
Cigar-shaped
of
Diagnosis
yeast.
Associated with activities that involve contact with soil, sphagnum moss,
decaying wood, or vegetation.
Gardeners, forestry workers, miners, animal health care providers most
at risk.
Raised skin lesions with proximal spread along lymphatic channels.
Recovery of microorganism from culture.
General
Considerations
Epidemiology. Sporothrix
schenckii , the causative agent of
sporotrichosis, is a ubiquitous fungus commonly found in the soil, on
sphagnum moss, on decaying wood, and on a variety of other
vegetation. It is found worldwide but prefers a temperate or tropical
infection.
CLINICAL
SYNDROMES
and
CUTANEOUS
disseminated
sporotrichosis
(Box 76-1 ).
SPOROTRICHOSIS
EXTRACUTANEOUS
SPOROTRICHOSIS
1.
OSTEOARTICULAR
SPOROTRICHOSIS
The joints commonly affected are the joints of the hand, elbow, ankle, and
knee. Onset is insidious, presenting with pain and swelling of a single joint
with minimal fever or systemic toxicity. Over time, a sinus
P.765
tract may develop and, if left untreated, other joints may be involved.
Differential diagnosis includes rheumatoid arthritis, gout, and tuberculosis.
Joint aspirations and synovial biopsies, often multiple, are required to
establish
More
the
diagnosis.
Common
Common
Extracutaneous sporothricosis:
nervous system
Disseminated
osteoarticular,
pulmonary,
and
central
2.
PULMONARY
SPOROTRICHOSIS
3.
CENTRAL
NERVOUS
SYSTEM
SPOROTRICHOSIS
DISSEMINATED
SPOROTRICHOSIS
Choice
Osteoarticular
Pulmonary
Nervous
System
Disseminated
Diagnosis
In patients with typical cutaneous syndrome of ascending lymphangitis,
demonstration of the characteristic appearance of the microorganism on
stains performed on tissue biopsy is highly suggestive of diagnosis.
Definitive diagnosis requires recovery of microorganisms from culture.
Multiple attempts to isolate the organisms may be necessary.
Several serologic testing procedures such as agglutination tests, ELISA,
complement fixation, precipitation, and immunodiffusion tests have been
developed to aid in the diagnosis of sporotrichosis. While these may prove
Treatment
Several therapeutic modalities such as local treatment, systemic therapy,
and surgery have been used for the treatment of sporotrichosis (Box 76-2 ).
A saturated solution of potassium iodide (SSKI) is an effective regimen for
cutaneous disease. Its mechanism of action is not well understood. SSKI
drops are taken orally, and the dose is progressively increased to a
maximum tolerated dose. Treatment is continued until the resolution of the
skin lesions.
More recently, itraconazole, a triazole antifungal agent, has become the
drug of choice for treatment of lymphocutaneous sporotrichosis. As stated
above, treatment should be continued until resolution of infection, which
usually takes 36 months. Itraconazole has been shown to be effective
therapy for cutaneous as well as visceral sporotrichosis, with the exception
of meningitis.
Osteoarticular sporotrichosis requires treatment with itraconazole or
amphotericin B, but relapses can occur. There have been reports of
successful treatment of osteoarticular sporotrichosis with intra-articular
BOX
76-3
Sporotrichosis:
Prevention
Prognosis
Prognosis is variable and difficult to generalize. Disseminated
sporotrichosis, if untreated, causes death.
Prevention
&
Control
REFERENCES
Coles BF et al: A multistate outbreak of sporotrichosis associated with
sphagnum moss. Am J Epidemiol 1992;136:475.
Heller HM, Fuhrer J: Disseminated sporotrichosis in patients with AIDS:
case report and review of the literature. AIDS 1991;5:1243.
P.767
Kauffman CA: Old and new therapies for sporotrichosis. Clin Infect Dis
1995;21:981.
Reed KD et al: Zoonotic transmission of sporotrichosis: case report and
review. Clin Infect Dis 1993;16:384.
Rex JH: Sporothrix
schenckii. In Mandel GL, Bennett JE, Dolin R:
Principles and Practice of Infectious Diseases , 4th ed. Churchill
Livingstone,
1995.
Werner AH, Werner BE: Sporotrichosis in man and animal. Int J Dermatol
1994;33:692.
Winn RE: A contemporary view of sporotrichosis. Curr Top Med Mycol
1995;6:73.
2001
McGraw-Hill
77
Fusarium,
Penicillium,
Paracoccidioides, & Agents of
Chromomycosis
Michael R. Keating MD
FUSARIUM
Essentials
Worldwide
INFECTION
of
Diagnosis
geographic
distribution.
General
Considerations
Clinical
Findings
Laboratory
Findings. Neutropenia is usually present at the
onset of the signs and symptoms of infection, but there are
no other commonly associated hematologic or chemistry
abnormalities.
Blood
cultures
P.769
More
Common
Less
Common
Rhinocerebral
infection
Central nervous system
involvement
Intra-abdominal
organ
involvement
Diagnosis
The diagnosis is confirmed by the recovery of Fusarium isolates
from blood or biopsy specimens. Skin lesions developing in the
setting of new fever in a neutropenic patient should be biopsied
for histopathology and culture. The recovery of Fusarium spp.
from sputum can suggest the diagnosis in the appropriate host
with a syndrome compatible with invasive fusariosis; however,
colonization of the respiratory tract can occur with this
organism.
Treatment
Amphotericin B is the treatment of choice (Box 77-2). Response
to therapy is usually poor, and in vitro susceptibility testing
suggests that more than half of the strains tested are resistant
to amphotericin B. It is unknown if the lipid preparations of
amphotericin B offer any therapeutic advantage, but patients
have been successfully treated with lipid preparations of
amphotericin B. The use of granulocyte colony stimulating
factors and granulocyte transfusions has been reported to be
Prognosis
Invasive fusariosis is a lethal disease. The overall mortality rate
according to the medical literature is > 70%.
First
Choice
Second
Choice
Comment
Treatment
with
granulocyte
colony
P.770
Prevention
&
Control
Because the skin and nails are potential portals of entry, before
chemotherapy-induced neutropenia, patients with significant
onychomycosis should be evaluated by a dermatologist for
Fusarium infection (Box 77-3). Futhermore, high-risk
neutropenic patients with skin trauma and contamination should
PENICILLIUM
Essentials
of
INFECTIONS
Diagnosis
Penicillium
marneffei infection found in both
immunocompetent and immunosuppressed patients.
P
Prophylactic
Measures
Isolation
Precautions
None
General
Considerations
laboratories.
Clinical
Findings
More
Common
Chronic
Fever
illness
Weight loss
Cutaneous
involvement
Generalized
lymphadenopathy
Anemia
Positive
Less
Common
blood
culture
Diarrhea
Pericarditis
Bone and joint involvement
Central nervous system
involvement
Diagnosis
The diagnosis of invasive disease by Penicillium spp. other than
P marneffei must be based on histologic evidence of tissue
invasion and recovery of the organism from tissue culture. In
addition, recovery from a sterile body fluid such as blood or
synovial fluid is suggestive of infection but must be interpreted
with caution in view of the frequency with which Penicillium spp.
contaminate laboratory specimens.
Infection with P marneffei occurs only in people who have lived
or traveled in the endemic areas of Southeast Asia and southern
China. An exposure history is critical in considering the
diagnosis. Blood cultures will establish the diagnosis, but other
specimens including bone marrow, skin, abscess fluid, lymph
nodes, sputum, and others may yield the organism. P marneffei
must be distinguished from Histoplasma
capsulatum, which it
closely resembles in the laboratory.
Treatment
The drug of
amphotericin
(Box 77-5).
the efficacy
marneffei Infection
First
Choice
Second
Choice
Comment
Prognosis
With early diagnosis and initiation of appropriate fungal
therapy, the prognosis is very good; however, among patients
in whom the diagnosis is delayed, the mortality rate is high.
Prevention
&
Control
PARACOCCIDIOIDOMYCOSIS
Essentials
Patients
of
usually
Diagnosis
immunocompetent.
General
fixation
or
immunodiffusion.
Considerations
Paracoccidioidomycosis
is
caused
by Paracoccidioides
Clinical
Findings
uncommon.
Patients with respiratory symptoms will present with cough,
purulent sputum production, and dyspnea (Box 77-6). Fever
may or may not be present. Many patients will have
nonspecific constitutional symptoms such as weight loss,
weakness, and malaise. Mucocutaneous involvement is
characterized by ulcerations in the mouth, cheilosis, and
dysphagia.
On physical examination, the pulmonary findings are often
less prominent than would be expected based on the
radiographic findings. Examination of the mouth may reveal
polymorphic ulcerations. The lips may be indurated and
painful. Lymphadenopathy is often present, and
spontaneous drainage commonly occurs. A variety of
cutaneous lesions may be seen including abscesses,
nodules, papules, ulcers, and verrucous lesions. It is very
common for pulmonary, mucocutaneous, and lymph node
involvement to coexist in the same patient.
Laboratory
Findings. Direct examination of sputum or
lymph node drainage with a potassium hydroxide smear may
reveal the yeast forms. Culture of sputum or drainage will
also be positive. Blood cultures may be positive in
disseminated disease, particularly among children and
young adults. Serologic tests will be positive in most
patients with infection.
Imaging. The chest x-ray will generally show diffuse
bilateral interstitial and alveolar infiltrates. Less frequently
encountered findings include multiple nodules, cavitation,
and hilar lymphadenopathy. Calcification occasionally occurs
but not as frequently as in histoplasmosis or tuberculosis.
Differential
Diagnosis. Tuberculosis may coexist with
paracoccidioidomycosis in as many as one-quarter of the
cases, and care must be taken to distinguish two diseases
that can resemble each other. The differential diagnosis also
includes histoplasmosis, blastomycosis, lymphoma,
leishmaniasis,
leprosy,
and
malignancies.
More
Common
Chronic
Fever
illness
Mucocutaneous involvement
nose, larynx)
Cutaneous
involvement
Lymphadenopathy
Pulmonary
Less
Common
(mouth,
involvement
Hepatosplenic
disease
CNS involvement
Bone and joint involvement
Arteritis
Diagnosis
The diagnosis of paracoccidioidomycosis can be suspected when
an appropriate clinical syndrome occurs in a patient who has
lived or traveled in Latin America. Given the syndrome's strong
propensity to become dormant and remain so for years, even a
remote history of exposure in the endemic area can be
considered significant. The presence of multiply budding yeast
cells on direct examination of sputum or pus is presumptive
evidence of paracoccidioidomycosis. These cells may also be
seen on histologic examination of a lymph node or other tissue.
Treatment
The azoles are now considered the treatment of choice for
paracoccidioidomycosis
(Box 77-7). In clinical trials, 95% of
patients responded to a standard ketoconazole regimen, and 8%
of patients relapsed. Itraconazole may be superior to
ketoconazole, but there is less experience with this agent. A
similar response rate has been observed but with a lower
relapse rate. Similar findings have been noted with fluconazole.
Paracoccidioidomycosis can also be treated with sulfonamides.
Although the response rate is excellent, there is a relapse rate
of ~ 15%. Therapy with sulfadiazine can be instituted and
continued for 4 weeks until a clear clinical response is detected.
The maintenance dose is continued for 35 years.
Amphotericin B can be used in life-threatening infections or in
patients who are intolerant of or have failed sulfonamide
therapy. Azole therapy should follow amphotericin therapy for
several months. Trimethoprim-sulfamethoxazole can be
substituted for sulfadiazine in both the initial and maintenance
phases of therapy and should be given lifelong in AIDS patients
with a history of paracoccidioidomycosis.
Prognosis
The prognosis for paracoccidioidomycosis is excellent when the
diagnosis is established early in the course of the disease and
therapy is promptly instituted. In patients with advanced
disease and a wasting syndrome characterized by weight loss,
fatigue, and malnutrition, the prognosis is less favorable but is
First
Choice
Second
Choice
Comment
Prevention
&
Control
prevent
primary
CHROMOMYCOSIS
Essentials
Patients
are
of
usually
Diagnosis
immunocompetent.
General
Considerations
Phialophora
verrucosa,
Botryomyces
caespitosus,
P.775
Prophylactic
Measures
Trimethoprimsulfamethoxazole
Isolation
None
Clinical
Precautions
Findings
chromomycosis
More
Less
Common
Common
Chronic infection
Foot involvement
Cauliflowerlike
appearance
Diagnosis
The diagnosis of chromomycosis requires scraping or biopsy.
The presence of the characteristic sclerotic body is diagnostic.
These are easily seen with a KOH stain, particularly when
collected from verrucous form of infection. Annular infections
tend to have a lower number of organisms and may require
biopsy. Scrapings and biopsy specimens submitted to culture
should be held in the mycology laboratory for 46 weeks
to allow sufficient time for growth to occur. There are no
serological tests to assist in the diagnosis of mucormycosis.
Treatment
Treatment of chromomycosis is difficult, and failure to
cure is common (Box 77-10). Early, localized infection
treated with wide surgical excision. Cryotherapy with
nitrogen has also been successful in eradicating early
achieve a
can be
liquid
infection.
More established infection will require antifungal therapy; 5flucytosine has been extensively used.
P.776
Many cases will have partial response, but relapse is common,
and resistance develops frequently. Retreatment with 5flucytosine is usually unsuccessful because resistance develops.
First
Choice
Second
Choice
Comment
Prophylactic
Measures
Isolation
Precautions
None
Prognosis
Untreated chromomycosis leads to a disfiguring, slowly
enlarging lesion. Elephantiasis can develop as a result of the
disruption and obstruction of lymphatics.
Prevention
&
Control
REFERENCES
Duong TA: Infection due to Penicillium
marneffei, an
emerging pathogen: review of 155 reported cases. Clin
Infect Dis 1996;23:125. (Authoritative review of the history,
epidemiology, mycology, clinical manifestations, diagnosis,
and treatment of Penicillium marneffei.).
Pseudallescheriasis.)
and
2001
McGraw-Hill
78
Dermatophytes
Scott D. Smith MS, MD
David A. Relman MD
Essentials
of
Diagnosis
General
Considerations
by
anthropophilic
dermatophytes.
genetic-susceptibility
markers;
abraded
skin;
P.778
footwear, or dressings; and the presence of other cutaneous diseases
like atopic dermatitis. The dermatophytes invade the keratinized
layers of skin by producing keratinases, enzymes that digest keratin.
While adhering to and invading host skin, the dermatophytes elicit a
diverse set of clinical responses. Most lesions are contained within a
certain anatomic boundary and may even be self-limited, but
widespread dermatophyte infection has been observed in patients with
AIDS, patients on immunosuppressive drug regimens, and those who
have endocrinopathies such as Cushing's disease. The pathogenic
features of superficial dermatophyte infections of the skin are
illustrated in Figure 78-1 .
Clinical
Findings
Figure
centrifigum,
circinate
lesions
with
erythematous
raised
KOH mount of skin scraping from leading edge and culture if indicated
Tinea unguium (onychomycosis)
T rubrum 1
T mentagrophytes 2
Small yellow spot begins at nail base; nail becomes brittle, friable,
thickened
Nail bed tumors, yellow-nail syndrome, pachyonychia congenita,
traumatic
onychodystrophy
KOH mount of nail shaving or nail bed detritus and culture if indicated
Other
nondermatophytes
Tinea versicolor
Pityrosporum ovale
P orbiculare (also called Malassezia furfur )
Not formally a dermatophyte
Begins as multiple small circular macules (white, pink or brown) that
enlarge radially
Usually
asymptomatic
May itch
Vitiligo, pityriasis alba, seborrheic dermatitis, secondary syphilis, and
pityriasis rosea
KOH mount of skin scraping
Wood's light = irregular pale yellow-white fluorescence; fades with
treatment (some lesions do not fluoresce)
Fungal id reaction
Not a dermatophyte at the local site but associated with certain tinea
infestations
Adults: vesicular eruption of the palms
Children: erythematous lichenoid papules
Adults: associated with tinea pedis
Children: associated with kerions of the scalp
Look for and diagnose the primary offending dermatophyte
1
Anthropophilic.
2 Zoophilic.
Geophilic.
Tinea
Type
Table
Figure
Dermatophytes
78-1.
Differential
Clinical
Presentation
Differential
Diagnosis
diagnosis
dermatophytoses.
for
Diagnosis
tanned skin. The lesions are usually asymptomatic, but they may itch
if there is inflammation.
Diagnosis
In addition to clinical recognition and diagnosis on clinical grounds, there
are three specific techniques that are useful in the work-up and more
definitive diagnosis of superficial mycoses: UV light examination, direct
microscopy, and culture. Direct examination of the patient's skin in a
darkened room by using UV light (a Wood's lamp) is useful only for
infectionsprimarily tinea capitis or corporiscaused by certain
species,
including M. audouinii, M canis , and T schoenleinii. These
infections give off a blue-green color.
Specimens for diagnosis by microscope or culture can be collected using a
razor or scalpel to scrape keratinized or flaking material from the leading
edge of the newest lesion. Nail scrapings are ideal if the nail is scraped
underneath the nail plate, initially to clean it and then to collect a
specimen onto a microscope slide or to inoculate culture. A few drops of
1020% KOH solution is placed on the slide to dissolve keratin. Heating
accelerates the process. This enables visualization of hyphae seen with
dermatophytes or of hyphae and spores seen in candidal and tinea
versicolor
infections.
Because KOH wet mounts cannot differentiate among dermatophyte
species, the organisms should be cultivated to reveal the distinguishing
forms of conidia. From a clinical perspective, it is usually not necessary to
identify the dermatophyte species, because topical and oral agents are
active against all of them. Species identification is important for scalp
infections, severe or inflammatory skin infections, and certain nail
infections, because systemic treatment is
P.782
P.783
necessary for scalp infections, treatment may be prolonged and
expensive, and species identification may enable prevention of zoophilic
infections. Some nail infections may be caused by a mold (eg,
Scopulariopsis spp.), which, despite being indistinguishable from
dermatophytoses on a gross visual basis, will not respond to the same
Tinea
Capitis
tonsurans;
Barbae
Corporis
indicated
Versicolor
Unguium
(Onychomycosis)
Choice
Second
Choice
measures
Treatment
The principles of treatment are outlined in Box 78-1 , according to the
specific clinical presentation. Most tinea infections involving the skin can
be treated with topical agents such as an imidazole twice a day for 2 or 3
weeks. Terbinafine is also available both in topical and oral formulations
and appears to be a more potent drug, requiring shorter dosing with
longer lasting clinical responses. Terbinafine and newer related drugs
block ergosterol synthesis at an earlier step than do the azole drugs.
If the infection is widespread, involving a large surface area, or if it is
particularly inflammatory, systemic drugs are indicated. For infections of
the hair and nails, dbridement is important prior to systemic
treatment. Several oral medications including itraconazole, fluconazole,
and terbinafine can be dosed on a daily basis or in so-called
pulsed regimens for effective treatment of infections of the
keratinized tissues. The concept underlying pulse dosing takes advantage
of drug deposition in the nail so that the total dose can be reduced;
elevated amounts of drug are given repeatedly for short intervals
corresponding to the length of time for a finger or toenail to grow. For
example, a slightly higher daily dose is given for 1 week each month for
the length of time estimated for the infected nail to grow again.
Treatment of tinea versicolor is with a 2.5% selenium sulfide suspension
applied to the entire skin surface from the lower posterior scalp area down
to the thighs for 10 min every day for 7 days. Another common regimen is
to apply the lotion and wash it off after 24 h, repeating once a week for a
month. Antifungal creams are useful. Single dose oral treatment with
ketoconazole, itraconazole, or fluconazole has also been shown to be
effective. Other important
P.784
adjunctive measures to minimize reinfection include discarding or boiling
frequently worn garments that are in contact with the skin. The lesions
may take months to clear as they result from depigmentation, which
persists despite eradication of the fungus.
Prophylactic
Measures
Isolation
Precautions
None
BOX 78-2 Prevention & Control of Dermatophytoses
Prevention
&
Control
REFERENCES
Aly R, Berger T: Common superficial fungal infections in patients with
AIDS. Clin Infect Dis 1996;22(Suppl 2):S128.
Assaf RR, Weil ML: The superficial mycoses. Dermatol Clin
1996;14(1):57.
Brautigam M: Randomised double blind comparison of terbinafine and
itraconazole for treatment of toenail tinea infection. Br Med J
1995;311:919.
Elewski BE: Onychomycosis: pathogenesis, diagnosis,
management. Clin Microbiol Rev 1998;11(3):415.
and
2001
McGraw-Hill
79
Pneumocystis
carinii
James J. Chamberlain MD
Kristen Ries MD
Essentials
of
Diagnosis
Pneumocystis
carinii, when examined using molecular
techniques, most closely resembles a fungus.
Stains of either bronchoalveolar-lavage (BAL) or
transbronchial-biopsy samples yield a diagnosis in > 90% of
patients and should be considered the gold standard in
diagnosis.
BAL with transbronchial biopsy increases diagnostic yield to
~ 100%.
P carinii has not yet been cultured in vitro.
Polymerase chain reaction (PCR) (especially on sputum)
increases sensitivity but reduces specificity.
The prophylactic use of aerosolized pentamidine reduces the
sensitivity of sputum and bronchoscopic samples.
General
Considerations
CLINICAL
P
SYNDROMES
CARINII
Clinical
PNEUMONIA
Findings
EXTRAPULMONARY P
INFECTIONS
CARINII
More
Common
Less
carinii
Common
Fever
Cough (usually
nonproductive)
Pneumothorax
(especially if
prophylactic
treatment
Dyspnea
(especially
with exertion)
Elevated lactate
dehydrogenase
Diffuse
interstitial
with pentamidine)
Pleural effusions rare
infiltrates on chest
radiograph
Diagnosis
The practice of diagnosing PCP morphologically by traditional
staining methods (silver methenamine and toluidine blue) of
induced sputum samples in HIV-infected individuals has fallen
out of favor. Although relatively simple and inexpensive, staining
of sputum samples induced by hypertonic saline inhalation is
clearly dependent on operator and laboratory experience, and
sensitivity varies tremendously between centers. These classic
staining techniques yield a diagnosis in only 3090% of
patients suspected of being infected with PCP. Subsequently, a
large number of patients may continue to be treated with
potentially toxic drug regimens without a definitive diagnosis.
The practice of indirect immunofluorescent stain with monoclonal
antibodies has increased the sensitivity of induced sputum
samples to ~ 70% or to > 90% in some reports.
Bronchoscopy with BAL with or without transbronchial biopsy has
become the gold standard in the diagnosis of PCP. Several
studies have demonstrated a sensitivity of > 90% for both BAL
results.
Treatment
The primary treatment of moderate to severe pulmonary or
extrapulmonary infection caused by P carinii remains the
combination of trimethoprim (TMP) and sulfamethoxazole (SMX),
either orally or intravenously (IV).
Several medications (atovaquone, trimetrexate, and
pentamidine) and combination regimens (dapsone + TMP and
clindamycin + primaquine) probably afford nearly equal efficacy
to TMP-SMX in mild to moderate PCP and may be better tolerated
in specific populations of patients (Boxes 79-2 and 79-3) .
TMP-SMX. TMP-SMX was the first regimen approved for use
in the treatment of PCP, and this regimen is still considered
the best initial treatment choice for PCP infection. If
tolerated, this combination should be regarded as the initial
treatment choice for all PCP infections.
In moderate to severe pulmonary infection with P carinii,
TMP-SMX has been shown to significantly improve survival
when compared with IV pentamidine (86% vs 61%) in
infections.
neutropenia,
and
gastrointestinal
complaints.
carinii Pneumonia
in Adults
Treatment
First
Choice
For mild to
moderate
infections:
Trimethoprim,
Comments
15
mg/kg/d, and
sulfamethoxazole,
100 mg/kg/d PO
or IV, three times
daily or four
times daily, for
1421 d (21 d
in AIDS)
For moderate to
severe infections
(see comments):
Trimethoprim as
above with or
without
Corticosteroids
(prednisone)
are currently
recommended
in patients
with PO <70
mm Hg or an
alveolararterial
oxygen
gradient (P(Aa)0) > 35 mm
Hg.
prednisone, 40
mg PO twice,
daily for 5 d then
20 mg PO daily
for 11 d
Second
Choice
Pentamidine,
34 mg/kg IV
Patients with
severe disease
should
probably
receive 4 mg
of petamidine.
Folinic acid
min) + folinic
acid (leucovorin),
20 mg/m/d PO or
IV divided every
must be
administered
at the
initiation of
6 h for 21 d
Atovaquone
suspension, 750
mg PO twice daily
trimetrexate
therapy and
continued for 3
d after
for 21 d
Clindamycin, 600
mg IV four times
daily or
300450 mg PO
four times daily,
+ primaquine, 15
mg PO daily for
21 d
Dapsone, 100 mg
PO daily +
trimethoprim 5
mg/kg PO three
times daily for 21
d
cessation of
therapy.
Atovaquone
should be
taken with
food; failure to
do so may
result in
threefold
reduction in
absorption.
Penicillin
No change; treat
Allergic
as above
carinii Pneumonia
Children
Treatment
Comments
First
Trimethoprim-
Steroids
Choice
sulfamethoxazole,
1520 mg
TMP75100 mg
SMX/ kg/d IV,
appear to be
beneficial in
moderate to
severe
disease
There are no
controlled
trials of
steroids in
young
children
Suggested
dosage 2
mg/kg/d for
710 days
followed by a
tapering
dose during
the next
1014 d
Second
Choice
Pentamidine
isethionate, 4 mg
base/ kg/d IVfor
1014 d
Alternatives:
trimethoprim and
dapsone; primaquine
and clindamycin;
trimetrexate and
folinic acid;
atovaquone; for
nonsevere
disease
1 Oral
Prognosis
Many clinical markers or scoring systems have been suggested to
diagnose and predict outcome in PCP. Most if not all of these
factors have been shown to have little value in the management
of disease. The degree of hypoxia is an important prognostic
factor that affects recommended treatment. The adjuvant use of
corticosteroids and choice of treatment regimen should be based
on whether the disease is classified as mild to moderate (PaO2 >
70 mm Hg and P[A-a]O 35 mm Hg) or moderate to severe
(PaO2 < 70 mm Hg or P[A-a]O 35 mm Hg). However, it is
probably better to err on the side of using corticosteroids.
Prevention
&
Control
infections.
Pentamidine
Isethionate.
Pentamidine
Adults
First
Choice
carinii
Children
TMP-SMX, 1 DS
tablet PO daily or
PO 3 times per
TMP-SMX, 5
mg TMP25
mg SMX/kg/d
week, usually on
Monday,
Wednesday, and
Friday
half given
every 12 h or
as single dose
daily for 3
consecutive
d/wk or 7 d/wk
Second
Choice
Pentamidine, 300
mg aerosolized via
nebulizer once per
Pentamidine,
300 mg
nebulized
month
Dapsone, 50100
mg PO daily or 100
mg PO two times
monthly or
dapsone 2
mg/kg (not to
exceed 100
mg) PO daily
REFERENCES
American Academy of Pediatrics, Committee on Infectious
Diseases: Pneumocystis. In Peter G: 1997 Red Book: Report
of the Committee on Infectious Diseases, 24th ed. American
Academy of Pediatrics, 1997.
Bozzette SA, et al: A randomized trial of three
antipneumocystis agents in patients with advance human
immunodeficiency virus infection. NIAID AIDS Clinical Trials
Group. N Engl J Med 1995;332:693.
Chien SM, et al: Changes in hospital admissions patterns in
patients with human immunodeficiency virus infection in the
era of Pneumocystis
carinii prophylaxis. Chest
1992;102:1035.
Dohn MN, et al: Oral atovaquone compared with intravenous
pentamidine for Pneumocystis
carinii pneumonia in patients
with AIDS. Ann Intern Med 1994;121:174.
Fulton B, Wagstaff AJ, McTavish D: Trimetrexate: a review of
its pharmacodynamic and pharmacokinetic properties and
therapeutic potential in the treatment of Pneumocystis
carinii
pneumonia. Drugs 1995;49(4):563.
Girard P-M, et al: Dapsone-pyrimethamine compared with
aerosolized pentamidine as primary prophylaxis against
Pneumocystis
carinii pneumonia and toxoplasmosis in HIV
infection. N Engl J Med 1993;328:1514.
Hughes W, et al: Comparison of atovaquone (566C80) with
trimethoprim-sulfamethoxazole for the treatment of
Pneumocystis
carinii pneumonia in patients with the acquired
immunodeficiency syndrome (AIDS). N Engl J Med
1993;328:1521.
Kennedy CA, Goetz MB: Atypical roentgenographic
manifestations of Pneumocystis
carinii pneumonia. Arch
Intern Med 1992;152:1390.
Kovacs JA, et al: Diagnosis of Pneumocystis
carinii
Lancet
1992;340:203.
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > A Protozoa > 80 - Malaria and Babesia
80
Malaria and Babesia
Gary W. Procop MD
David H. Persing MD, PhD
PLASMODIUM SPP.
Exposure history, such as travel, recent transfusion, or
living in close proximity to an international airport.
Nonfalciparum malaria: chills and fever spikes, followed by
defervescence and fatigue; symptoms may be cyclic every
4872 h.
Falciparum malaria: fever spikes and chills, often noncyclic
and associated with rapidly progressive systemic symptoms.
Detection and identification of a Plasmodium species in a
thick and thin blood smear, respectively.
Molecular detection of P falciparum 's histidine-rich protein
by enzyme-linked immunosorbent assay (ELISA) or
Plasmodium DNA by polymerase chain reaction (PCR)
followed speciation by probe hybridization or DNA
sequencing.
General
Considerations
Giemsa-stained
preparations,
small,
erythrocytes
predominantly
or relative
RBCs
Infected
RBCsize
Normocellular
Normocellular
Increased
RBC
stippling
Coarse
dots)
None
Fine
dots,
commalike,
occasionally
present
(Maurer's
present
stippling
(Schuffner's
stippling P ovale )
Rings
Parasite
load
Often high
Often low
Intermediate
> 1 organism/cell
Common
Low
Occasional
Appliqu
forms
Present
Usually
absent
Usually
absent
Advanced
forms
Advanced
forms
forms
N/A
Basket, band, and indistinct amoeboid forms
Indistinct
Number
forms
of
merozoites/cell
N/A
612 (average 8)
P vivax: 1224 (average 16)
P ovale: 812 (average 8)
Amount of RBC occupied by schizont
N/A
Entire cell
P vivax: entire cell
P ovale: fills 2/3 of cell
Distinctive
bananashaped
Present
Absent
Absent
Other
Features
Cycle of fever
Usually
without
72 h
48 h
Hypnozoitesb
Absent
established
cycle
gametocyte
Absent
Present
a
80-1.
P
falciparum
P
malariae
P vivax/P
ovale
magnification.)
of Plasmodium species.
Figure
slightly
FALCIPARUM
MALARIA
Clinical
Findings
parasitosis.
NONFALCIPARUM MALARIA
P OVALE, P MALARIAE )
Clinical
Findings
(P
VIVAX,
-associated
nephrotic
P vivax/ P ovale
Cyclic episodes that consist of chills followed by fever, which is
followed by defervescence and diaphoresis; cyclic every 48 h
P malariae
Cyclic episodes that consist of chills, followed by fever, which is
followed by defervescence and diaphoresis; cyclic every 72 h;
possible
immunecomplexmediated
glomerulonephritis
P falciparum
Continuous fevers with irregular spikes, possible
hyperparasitemia with microvascular damage and compromise.
This is a medical emergency in the nonimmune. Microvascular
compromise may lead to central nervous system damage, renal
and pulmonary failure, and death.
BOX
80-1
Plasmodium-Associated
Differential
Syndromes
Diagnosis
Nonfalciparum
malaria. Many of the signs and symptoms of
nonfalciparum malaria are nonspecific. There are many causes
of anemia and hepatosplenomegaly. Malaria is endemic in many
underdeveloped areas; indigenous people in these countries
may suffer from protein-calorie malnutrition and are exposed to
a wide variety of infectious agents. Impoverished children with
and
of advanced amoeboid
malarial pigment.
forms or schizonts,
form pigment. These
Diagnosis
The first clue to clinicians of the possibility of malaria is often
from a history of travel to a malaria-endemic area. Patients
should be asked
should probe for
endemic areas in
have traveled to
speciation.
Treatment
In the treatment of malaria, specific antiplasmodial therapy and
supportive care are essential to reduce morbidity and mortality.
The basic principles of antiplasmodial therapy are defined
below. Therapeutics and dosages for the most commonly used
antimalarial agents are listed in Box 80-2 . It should be noted
that antimalarial drugs exist in both salt and base formulations,
and potentially dangerous dosing errors may occur unless care
is taken. Updated information regarding the treatment and
prophylaxis of malaria are available through the Centers for
Disease Control and Prevention and the World Health
Organization.
P vivax, P ovale, P malariae , and chloroquine-sensitive P
falciparum. Chloroquine phosphate is given to eradicate the
RBC phase. Oral therapy is usually sufficient for infections with
P vivax, P ovale , and P malariae and for P falciparum infections
that are not severe. Intravenous administration of
antiplasmodial agents should be used for patients with severe
falciparum malaria. Side effects of chloroquine may include
gastrointestinal disturbances, pruritis, dizziness, and headache.
Chloroquine resistance is widespread among P falciparum and
rarely has been reported for P vivax. Alternative regimens
include mefloquine and quinine. Patients infected with either P
vivax or P ovale must also be given primaquine phosphate to
eradicate hepatic hypnozoites. The failure to use primaquine
may result in malarial relapse at a later date. Primaquine
phosphate may cause hemolytic anemia in patients with
glucose-6-phosphatase deficiency; additional side effects
include gastrointestinal and central nervous system
disturbances. In infections caused by these organisms during
pregnancy, chloroquine is the drug of choice, and quinine is an
in
pregnancy.
Prognosis
The prognosis of nonfalciparum malaria is generally good. These
organisms are usually responsive to therapy. Relapses of P
vivax or P ovale malaria can be avoided with appropriate
Prevention
&
Control
Choice
Therapy
Children
Adults
Control
Measures
BABESIA SPP.
Essentials
Nonspecific
of
Diagnosis
clinical
manifestations.
General
Considerations
white-tailed
expanding
of both the
reservoir also
Clinical
Findings
More
Common
Asymptomatic
Less
Common
80-4
BabesiaAssociated
Syndrome
Diagnosis
Many Babesia infections are subclinical and are discovered
incidentally. Babesiosis should be suspected in patients with
mild, nonspecific symptoms who have recently visited endemic
wooded areas and report a tick bite. Babesiosis should be
considered in patients who have recently received an RBC
transfusion. Babesia species, like Plasmodium species, may also
be transmitted by this blood product. The symptoms of
babesiosis are nonspecific. Therefore the definitive diagnosis of
babesiosis is made in the laboratory.
Treatment
Mild Babesia infections in immunocompetent individuals usually
resolve without antimicrobial therapy. In cases of severe
disease or in immunocompromised patients, the combination of
clindamycin and quinine is the treatment of choice (Box 80-5 ).
The clindamycin may be given orally, intravenously, or
intramuscularly. Intravenous quinidine may also be used.
Prognosis
The vast majority of patients infected by B microti have
subclinical infections that usually resolve without incident. The
prognosis for immunocompromised
P.806
individuals and the elderly is guarded, because these patients
may have a more severe course. Patients who are coinfected
with B burgdorferi carry a worse prognosis than do patients
infected by either organism alone. Prognostic information is not
available for infections caused by the WA-1 agent because so
few cases have been reported. Splenectomized patients who
may be infected by B divergens in Europe have a grave
prognosis.
First
Choice
Adults
Prophylactic
Measure
Prevention
&
Control
The avoidance of outdoor activities in tick-infested, Babesia endemic areas is the most effective means of prevention (Box
80-6 ). If avoidance of these areas is impractical, tick repellents
should be used, and appropriate clothing should be worn. After
leaving tick-infested areas, one should perform a thorough body
and scalp search for ticks.
REFERENCES
Breman JG, Campbell CC: Combatting severe malaria in
African children. Bull WHO 1988;66:611.
Gelfand JA: Babesia. In Mandell GL, Bennett JE, and Dolin R,
Principles and Practice of Infectious Diseases , 4th ed.
Churchill Livingstone, 1995.
Krause PJ et al: Concurrent Lyme disease and babesiosis:
evidence for increased severity and duration of illness. JAMA
1996;275:1657.
Krogstad DJ: Plasmodium species (malaria). In Mandell GL,
Bennett JE, and Dolin R, Principles and Practice of Infectious
Diseases , 4th ed. Churchill Livingstone, 1995.
Parra ME, Evans CB, Taylor DW: Identification of Plasmodium
falciparum histidine-rich protein 2 in the plasma of humans
with malaria. J Clin Microbiol 1991;29:1629.
Persing DH et al: Detection of Babesia microti by polymerase
chain reaction. J Clin Microbiol. 1992;30:2097.
Pruthi RK et al: Human babesiosis. Mayo Clin Proc
1995;70:853.
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > A Protozoa > 81 - Toxoplasma gondii
81
Toxoplasma
gondii
Jose G. Montoya MD
General
Considerations
in
Clinical
Findings
or
generalized
lymphadenopathy
Chorioretinitis
Intensely white focal retinal lesions with overlying vitritis,
with or without associated scars; may result from
reactivation of congenital or postnatally acquired disease or
from recently acquired acute disease
Myocarditis
Arrythmias,
pericarditis,
heart
failure
Polymyositis
Patients with acute toxoplasmosis have developed
polymyositis/dermatomyositislike
syndromes
Systemic
Lowgrade fever, general malaise, headache, sore throat,
myalgia
immunity
impairment
Chorioretinitis
Can present atypically and/or with significant retinal
necrosis
Myelopathy
Cervical, thoracic, or lumbar
Pneumonitis
Interstitial
infiltrates
Systemic
Fever, multiorgan involvement,
and septic shocklike syndrome
acute
respiratory
failure,
Pregnant
Asymptomatic
90% of acute infection goes unrecognized
Lymphadenitis
Regional
or
generalized
lymphadenopathy
Fetus
Neurologic
disease
Generalized
disease
disease
disease
Fever, hepatosplenomegaly,
thrombocytopenia,
anemia
1
exam,
lymphadenopathy,
jaundice,
Syndromes
involved are
axillary, and
cervical,
inguinal.
suboccipital, supraclavicular,
Lymphadenopathy
P.810
IgM
result
Interpretation and
Recommendation
leukoencephalopathy,
respectively.
Differential
The
differential
Diagnosis
diagnosis
of
toxoplasmic
lymphadenitis
P.813
includes lymphoma,
mononucleosis, CMV
disease, sarcoidosis,
Complications
In rare instances, toxoplasmosis causes myocarditis,
polymyositis, pneumonitis, hepatitis, or encephalitis in
healthy
Treatment
Infection in Immunocompetent Adults and Children.
Immunocompetent adults and children with toxoplasmic
lymphadenitis do not require treatment unless symptoms
are severe or persistent. Infections acquired by laboratory
accident or transfusion of blood products are potentially
more severe, and these patients should always be treated.
The combination of pyrimethamine, sulfadiazine, and folinic
acid for 46 weeks is the most commonly used and
recommended drug regimen (Box 81-2 ). Treatment should
be administered for 24 weeks, followed by reassessment
of the patient's condition.
The decision to treat active toxoplasmic chorioretinitis
should be based on the results of an examination performed
by an ophthalmologist. Pyrimethamine and sulfadiazine plus
folinic acid are commonly used for this syndrome.
Lymphadenitis
None
No therapy1
No therapy1
Chorioretinitis
(active),
myocarditis,
polymyositis,
systemic2
Pyrimethamine PLUS
Loading dose: 2 mg/kg/d (maximum, 50 mg) for 2 days,
then maintenance, 1 mg/kg/d (maximum 25 mg)
Loading dose: 75100 mg over 24 h, followed by 25 to 50
mg/d
Sulfadiazine3 PLUS
Loading dose: 75 mg/kg, then maintenance, 50 mg/kg every
12 h (maximum 4 g/d)
Loading dose: 24 g initially, followed by 1 g four times
per day
Folinic
acid
mg/d
Corticosteroids
(if
indicated)
Syndrome
Drug
Children
Adults
Drug
Dosages
Pyrimethamine PLUS
Sulfadiazine1 PLUS
Folinic acid
Loading dose: 2 mg/kg/d (maximum, 50 mg) or 2 d, then 1
mg/kg/d for 2 or 6 mo. After 2 or 6 mo, 1 mg/kg/d every
Monday, Wednesday, and Friday
50 mg/kg every 12 h
520 mg 3 times weekly
Corticosteroids (if indicated)
1 mg/kg/d in 2 divided doses
1 Clindamycin is an alternative in patients allergic to
sulfonamides.
Drug
Dosages
Prevention
&
Control
12 h (maximum 4 g/d)
Loading dose: 24 g initially, followed by 11.5 g four
times per day
Folinic
acid
Children
Adults
Form
Preventive
Measure
Regimen
REFERENCES
Dubey JP, Lindsay DS, Speer CA: Structures of Toxoplasma
1997;35:174.
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > A Protozoa > 82 - Pathogenic Amebas
82
Pathogenic
Amebas
Christopher R. Fox MD
Merle A. Sande MD
ENTAMOEBA
ENTAMOEBA
Essentials
of
HISTOLYTICA &
DISPAR
Diagnosis
General
Considerations
cyst or a trophozoite. Infection is generally through fecaloral spread with ingestion of the cyst form, which is
resistant to killing by the low pH of the stomach. Within the
small bowel, the cyst divides into trophozoites, which then
colonize the large intestine. The trophozoites may
subsequently encyst and be shed into the stool. Once shed,
they may remain viable for weeks to months.
During acute colitis, trophozoites may be shed into the
stool. Unlike the cyst, the trophozoite cannot live outside
the host because it is rapidly killed by poor environmental
conditions and, if ingested, is degraded in the acid stomach
environment.
CLINICAL
SYNDROMES
Common
(cough,
pleuritic
chest
pain,
anchovy
paste effusion)
Peritoneal (abdominal painranges from mild to acute)
Less
Common
Fever
Volume depletion
Ameboma
Megacolon
Perforation
Diarrhea
Hepatomegaly
Pericardial (fever, chest pain, congestive heart failure,
tamponade)
Cerebral (change in mental status, focal neurologic deficits)
Genitourinary (painful ulcers with profuse discharge)
Intestinal
Hepatic
Extrahepatic
INTESTINAL
Clinical
DISEASE
Findings
AMEBIC
LIVER
Clinical
Findings
ABSCESS
cancer.
Diagnosis
The diagnosis of intestinal infection with E histolytica or E
dispar is made by demonstration of cysts or trophozoites in the
stool or by examination of biopsy specimens of mucosal tissue.
Amebic trophozoites are destroyed by many agents, including
antibiotics, antidiarrheal agents, barium, and tap water.
Therefore, stool specimens should be examined by preparing
wet mounts of specimens within 20 min of collection and
examining immediately. Staining with iodine and trichrome
maximizes the yield of positive specimens. Pathogenic
trophozoites of E histolytica may be distinguished from
nonpathogenic species by the presence of ingested erythrocytes
within the organism.
Serology is useful in diagnosis of E
histolytica
infection.
Treatment
Treatment of amebic disease requires both the elimination of
Prognosis
Although infection with E histolytica can be debilitating, it is
generally not life threatening. Once infection is identified,
effective treatment exists. Relapse or reinfection is not unusual.
Only a small minority of patients develops severe complications,
such as colonic perforation, toxic megacolon, ruptured hepatic
abscess, or cerebral amebiasis.
Prevention
&
Control
Choice
Asymptomatic
Cyst Passage
Intestinal
Disease
Hepatic
Extrahepatic
First
Choice
Intestinal
Disease
Hepatic
Extrahepatic
Prophylactic
Measures
Precautions
under
development
PATHOGENIC
FREE-LIVING
ACANTHAMOEBA
AMEBAS
INFECTION
NAEGLERIA
Naegleria
FOWLERI
INFECTION
REFERENCES
Marciano-Cabral F, Petri WA Jr: Free-living amebae. In
Mandell GL, Bennett JE, Dolin R: Principles and Practice of
Infectious
Diseases , 4th ed. Churchill Livingstone, 1995.
Ravdin JI: Amebiasis. Clin Infect Dis 1995;20:1453.
Reed SL: Amebiasis: an update. Clin Infect Dis 1992;14:385.
Reed SL, Wessel DW, Davis CE: Entamoeba
histolytica
infection and AIDS. Am J Med 1991;90:269.
Seidel J: Primary amebic meningoencephalitis. Pediatr Clin
North Am 1985;32:881.
Warhurst DC: Diagnosis of amebic infection. In Rickwood D,
Practical
Approach.
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > A Protozoa > 83 - Cryptosporidium, Cyclospora, & Isospora
Species & Microsporidia
83
Cryptosporidium, Cyclospora, &
Isospora Species & Microsporidia
Stephanie Boade Silas MD
DeVon Hale MD
Within the last decade, the AIDS epidemic has heightened awareness of
several gastrointestinal spore-forming protozoan pathogens. The genera
Cryptosporidium,
Isospora , and Cyclospora are members of the subclass
Coccidia and phylum Apicomplexa; the microsporidia are a group of
organisms belonging to the phylum Microspora. The spectrum of disease
caused by these protozoans goes beyond gastrointestinal manifestations,
and the significance of these protozoan infections is becoming increasingly
appreciated in both immunocompromised and immunocompetent hosts.
CRYPTOSPORIDIUM
Essentials
of
Diagnosis
transmission.
Patients at risk for person-to-person transmission include household
contacts, sexual contacts, health care workers, and children in day
care.
Symptoms are prolonged and more severe in immunocompromised
patients.
Acid-fast staining of fixed stool specimens allows identification of
oocysts; immunofluorescence and enzyme-linked immunosorbent assay
techniques are also available.
General
Considerations
More
Common
Watery diarrhea
Abdominal pain
Nausea
Vomiting
Fever
AIDS patient
Right upperquadrant pain
Fever
Nausea/vomiting
High alkaline phosphatase
Immunocompromised
Cough
Dyspnea
Hoarseness
Less
Common
Malaise
Weight loss
Myalgia
Headache
Malabsorption
Diarrhea
High bilirubin
Sinusitis
Laryngotracheitis
Enteric
BOX
83-1
Cholecystitis
Respiratory
Cryptosporidiosis
CLINICAL
Syndromes
SYNDROMES
1.
ENTERIC
Clinical
CRYPTOSPORIDIOSIS
Findings
prolonged
P.826
considerably more severe in compromised patients. Patients complain
of watery diarrhea in variable quantities of 25 L/day leading to
significant dehydration. Abdominal cramps, malaise, low-grade fever,
and anorexia are frequently reported. Nausea, vomiting, myalgia,
headache, and weight loss may also occur. Symptoms are usually selflimited in immunocompetent hosts, lasting 514 days, although cases
lasting several months have been reported in normal hosts. Oocysts
can still be found in stool 2 weeks after symptom resolution.
Laboratory
cryptosporidiosis.
2.
CHOLECYSTITIS
Clinical
Findings
Diagnosis.
Microsporidial
and
cytomegalovirus
infections
3.
RESPIRATORY
INFECTION
Diagnosis
The majority of diagnoses of C parvum infection are made by identification
of the organism in stool specimens (Table 83-1 ). Stool should be
examined while it is fresh or fixed in 10% formalin or polyvinyl alcohol.
Oocysts can be identified by light microscopy without specific staining but
are more readily seen with modified acid-fast staining. Phase-contrast
microscopy reveals birefringent oocysts. Oocysts in duodenal aspirates or
respiratory secretions can be similarly identified. Submitting three to four
separate stool samples has been recommended for increased diagnostic
yield. However, in a study of AIDS inpatients, one stool specimen resulted
in 96% sensitivity, increasing to 100% with only two specimens. Orders
should specify suspected C parvum because most laboratories do not
routinely
use
acid-fast
staining.
83-1.
Laboratory
diagnosis
of
cryptosporidiosis.
Figure
a routine ova and parasite exam. They are acid-fast positive but are most
easily detected with a direct fluorescent antibody stain. This picture
compares the size of the C parvum oocyst (46 m) with that of a
Giardia cyst (912 m), using a combined-fluorescent-antibody stain
(Meriflour stain reproduced with permission from Meridian, Inc.).
P.827
Hematoxylin and eosin staining of intestinal biopsy specimens reveals
basophilic organisms on the brush border that appear to project into the
lumen because of the intracellular but extracytoplasmic location of the
organism. Direct immunofluorescence can also be used on these biopsy
specimens, and electron microscopy provides greater detail. However, the
invasiveness of biopsy is rarely warranted and is not 100% sensitive.
Serologic antibody identification is available for C parvum infection but is
still investigational and not clinically useful for diagnosis due to the
persistence of antibody after infection. It is valuable as an epidemiologic
tool, however.
Treatment
No reliable treatment is available at this time for cryptosporidiosis (Box
83-2 ). Supportive care with fluids and antidiarrheal agents can be offered
while awaiting resolution in immunocompetent hosts or while addressing
the underlying etiology of immunosuppression in compromised hosts.
Paromomycin sulfate is currently the drug of choice for C parvum ,
surpassing spiramycin, for which there are no controlled studies.
Choice
Choice
Children
Prognosis
Although cryptosporidiosis is self-limited in immunocompetent patients,
patients with AIDS with enteric cryptosporidiosis present with disease, the
Prevention
&
Control
C parvum oocysts are 30-fold more resistant to chlorine than are Giardia
cysts. Oocysts are killed in water kept above 65C for 30 min as well as
water boiled for 1 min at any altitude. Oocyst death is also reported in
water kept at < 20C for 30 min, although more recent information
suggests greater resistance to freezing than previously thought (Box 83-3
).
Enteric precautions and good hygiene should reduce most person-to-person
transmission as well as animal-to-human exposures because family
contacts account for 50% of secondary cases. Also, apple juice and
cider should be pasteurized or boiled before consumption. No prophylactic
regimen for patients with AIDS is yet available, although paromomycin
sulfate and azithromycin are being studied. Immunocompromised patients
should be instructed to drink bottled or boiled water if water supplies are
suspect.
Prophylactic
Measures
Precautions
No specific measures
Good hygiene
BOX 83-3 Prevention & Control of Cryptosporidiosis
P.828
CYCLOSPORA
Essentials
of
Diagnosis
General
Considerations
Clinical
Findings
cryptosporidiosis,
isosporiasis,
microsporidiosis,
and
sarcocystosis.
Diagnosis
Diagnosis is made by identification of the Cyclospora oocyst in fresh or
iodine-preserved stool, duodenal aspirates, or small-bowel biopsies. With
acid-fast or safranin O staining, oocysts can be seen as 10 m spheres
with clusters of refractile globules. The oocysts autofluoresce blue under
UV light with a 365-nm excitation filter (Table 83-2 ).
More
Common
Cyclical diarrhea
Fatigue
Anorexia
Less
Common
Dyspepsia
Nausea
Abdominal cramps
Weight loss
Vomiting
Myalgia/arthralgia
BOX
83-4
Oocysts
Cyclosporiasis
are
Syndromes
10-mdiameter
nonrefractile
spheres
that
contain
infection.
Treatment
TMP-SMX is the first-line treatment for cyclosporiasis, with symptom
resolution noted 23 days into therapy (Box 83-5 ). Immunosuppressed
patients may require long-term suppressive therapy owing to an increased
relapse rate. In addition to TMP-SMX, metronidazole, tinidazole, and
ciprofloxacin hydrochloride have also been reported to stop oocyst
excretion.
Prognosis
Infection is generally self-limited in immunocompetent hosts, but
prolonged diarrhea with possible symptoms of malabsorption may occur in
immunocompromised
patients.
Prevention
&
Control
Choice
Children
Prophylaxis
Measures
Agricultural measures to
raspberries are ongoing
Isolation
decrease
waterborne
contamination
of
Precautions
No specific measures
Good hygiene
BOX 83-6 Prevention & Control of Cyclospora and Isospora spp.
and Microsporidia
ISOSPORA
Essentials
of
Diagnosis
General
Considerations
infections.
Clinical
Findings
More
Common
Diarrhea
Malaise
Anorexia
Less
Common
Abdominal
cramps
Weight loss
Headache
Vomiting
Flatulence
Chronic diarrhea
Eosinophilia
Malabsorption
BOX 83-7 Isosporiasis Syndromes
Diagnosis
Diagnosis of isosporiasis depends on identification of the oocyst in stool by
wet mount with subsequent confirmation using modified acid-fast or
trichrome staining. Colonoscopy aspiration or the duodenal string test may
be helpful to obtain the necessary sample. Oocysts autofluoresce in UV
light when viewed through a 450- to 490-nm excitation filter (Table 83-3 ).
Treatment
TMP-SMX has been shown to be effective treatment (Box 83-8 ). Patients
with AIDS have a 50% chance of relapse, and low-dose suppressive
treatment with TMP-SMX, pyrimethamine-sulfadoxine, or pyrimethamine
alone is recommended. Alternative treatments include metronidazole,
ciprofloxacin hydrochloride, roxithromycin, and diclazuril.
Prognosis
Untreated isosporiasis in the immunocompromised patient can lead to
severe malnutrition and dehydration and may be fatal.
Prevention
&
Control
MICROSPORIDIA
Essentials
of
Diagnosis
General
Considerations
microsporidial
infections
have
all
been
identified.
First Choice
TMPSMX 160/800 orally four times daily 10 d
TMP, 5 mg/kg; SMX, 25 mg/kg orally twice daily 7 d
Second Choice
Pyrimethamine, 75 mg orally once daily 10 d
Prophylaxis in AIDS
TMPSMX, 160/800 orally once daily 3/wk
Pyrimethamine/sulfadoxine, 25/500 orally
Pyrimethamine, 25 mg orally daily
Adults
once
daily
3/wk
Children
isolated from the cerebrospinal fluid and the urine. Computed tomography
of the brain and electroencephalography were normal. Corneal infection
has been caused by Nosema spp., Microsporidium
ceylonensis , and
Microsporidium
africanum. Patients have presented with decreased visual
acuity, conjunctivitis, and corneal ulcers. Corneal biopsy reveals the
organism.
Patients presenting with generalized muscle weakness have been
diagnosed with myositis caused by Pleistophora spp. Laboratory tests
revealed normal
P.833
creatine kinase levels, and electromyograms showed myopathy. Muscle
biopsies revealed scarring, fibrosis, inflammation, and Pleistophora
infiltrate. Self-limited diarrhea caused by E
an immunocompetent host. A patient with
who had undergone allogenic bone marrow
on autopsy to have microsporidial infection
acuity
muscle
weakness
diarrhea
Nosema
spp.
Pleistophora
spp.
E bieneusi
CLINICAL SYNDROMES
PATIENTS
IN
HIV-INFECTED
pulmonary
infection,
E bieneusi
S intestinalis
E bienusi
S intestinalis
E bienusi
E cuniculi
E hellem
Pleistophora
spp.
sensation
keratoconjunctivitis,
and
myositis
(Box 83-
Photophobia
Blurry vision
Diffuse
Enteric
muscle
weakness
Biliary
Pulmonary
Keratitis/Conjunctivitis
Myositis
4.
GASTROINTESTINAL
INFECTION
Clinical
Findings
Signs and Symptoms. Symptoms can persist over months and are
associated with anorexia and a 1020% weight loss. The diarrhea is
usually loose and watery, with patients reporting 120 stools/day.
The diarrhea is worse in the mornings and exacerbated by eating. A
crampy abdominal pain can precede defecation. Nausea and vomiting
are rarely present, and patients are afebrile.
Laboratory
Findings. Stool specimens are negative for leukocytes or
erythrocytes. Serum electrolytes can reveal low potassium,
magnesium, and
P.834
zinc. Malabsorption is indicated by abnormal D-xylose absorption, low
B 12 levels, and increased fecal fat.
Differential
Diagnosis. Differential diagnosis includes C parvum and
other coccidial protozoa. Coinfection with Mycobacterium
avium
complex, Giardia spp., and C parvum in the small bowel and
cytomegalovirus
and C parvum in the large bowel has been reported.
Complications. Complications of gastrointestinal infection include
5.
BILIARY
INFECTION
Clinical
Findings
6.
PULMONARY
INFECTION
7.
KERATOCONJUNCTIVITIS
8.
sinusitis,
nephritis,
cystitis
MYOSITIS
Diagnosis
The small size of the Microsporidium spore makes diagnosis difficult (Table
83-4 ). The sensitivity and specificity of different identification techniques
are not known. Microsporidial spores are gram positive and birefringent,
and they have a positive periodic acid-Schiffstaining polar body. Spores
can be found in stool, duodenal aspirates, urine, respiratory secretions,
and conjunctival scrapings. Diagnostic yield may be enhanced by collecting
three stools daily over 3 subsequent days. Spore concentration and
sedimentation techniques can increase yield. Weber's modified trichrome,
Gram, Giemsa, and chitin-binding fluorochrome stains have all been used
successfully to identify spores. Diagnostic yield can be increased by
preserving stool in formalin, pretreating in 10% potassium hydroxide, and
centrifuging for 5 min before staining with the Weber's modified trichrome
stain. Biopsy specimens can be similarly stained, but sensitivity may be
decreased due to normal-appearing mucosa. If < 25 spores are identified
from a stool specimen per coverslip, the likelihood of identifying organisms
by electron microscopy of a biopsy specimen is low. E bieneusi usually
involves the distal duodenum and proximal jejunum, and S intestinalis can
also involve the colon.
Electron microscopy can more readily identify the small spores and is
useful in speciation. Immunofluorescence and polymerase chain reaction
techniques are also valuable for speciation.
Treatment
Microsporidial treatment efficacy is anecdotal at this time (Box 83-11 ).
Albendazole has had the best success thus far in alleviating
gastrointestinal and biliary symptoms. However, eradication of spores is
rare, and relapse occurs 12 months after completion of 4 weeks of
83-4.
Adults
Children
Prevention
&
Control
REFERENCES
Abramowitz M (editor): Drugs for parasitic infections. Med Lett Drugs
Ther 1995;37:961.
Blackman E et al: Cryptosporidiosis in HIV-infected patients: diagnostic
sensitivity of stool examination, based on number of specimens
submitted. Am J Gastroenterol 1997;92(3):451.
Bryan RT: Microsporidia. In Mandell GL, Bennett JE, Dolin R: Principles
and Practice of Infectious Diseases , 3rd ed. Wiley, 1995.
Bryan RT: Microsporidiosis as an AIDS-related opportunistic infection.
Clin Infect Dis 1995;21(suppl 1):S62.
Carter PL et al: Modified technique to recover microsporidia spores in
sodium acetate-acetic acidformalin-fixed fecal samples by light
microscopy and correlation with transmission electron microscopy. J
Clin Microbiol 1996;34(11):2670.
Dupont HL et al: The infectivity of Cryptosporidium
volunteers. N Engl J Med 1995; 332:855.
parvum in healthy
Am
Clin
1996;25:691.
of
of
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > A Protozoa > 84 - Giardia
84
Giardia
Stephanie Boade Silas MD
DeVon Hale MD
Essentials
of
Diagnosis
General
Considerations
CLINICAL
SYNDROMES
1.
ACUTE
Clinical
GIARDIASIS
Findings
and
blood.
Differential
Diagnosis. C parvum, rotavirus, and toxigenic
Escherichia coli may all have similar presentations.
Complications. Rare associations with urticaria and
reactive arthritis have been reported in giardiasis. Biliary
tract disease and pancreatitis have been reported, as have
retinal arteritis and iridocyclitis. Gastric infections have
been seen in G lamblia patients with achlorhydria.
Acute
More
Common
2.
Chronic
Diarrhea
Malaise
Flatulence
Abdominal
Diarrhea
Alternating
diarrhea with
constipation
cramps
Abdominal pain
worsening by
eating
Malaise
Less
Nausea
Malabsorption
Common
Weight loss
Vomiting
Urticaria
Macrocytic anemia
Lactose
intolerance
Weight loss
Headache
CHRONIC
GIARDIASIS
Clinical
Findings
world.
Diagnosis
The key to diagnosis of G lamblia infection is the identification
of trophozoites or cysts, both of which can be seen in stools by
standard ova and parasite exam (Table 84-1). Trophozoites
have a short survival time outside the small bowel when not
contained within cysts and are more likely to be seen in fresh
wet mounts of liquid stool. Semiformed stool may be preserved
in formalin or polyvinyl alcohol. Staining with trichrome or iron
hematoxylin reveals cysts. Formalin or zinc flotation
concentration techniques may increase the yield of diagnosis.
Generally, one stool exam has a 5070% diagnostic yield,
which improves to 8590% after 3 stools collected over 23
days because of cyclic shedding. Purged samples have no effect
on diagnostic yield.
Enzyme immunoassay and direct fluorescent-antibody assay kits
are commercially available for testing for G lamblia infection.
Both methods have reported sensitivities of 87100% and
Table
alcohol;
IFA,
immunofluorescent
antibody
assay
Treatment
Historically, quinacrine hydrochloride has been the drug of
choice for the treatment of giardiasis, with 90% efficacy.
However, this drug is no longer produced in the United States.
Despite having never received a Food and Drug Administration
indication for giardiasis, metronidazole is the first-line
treatment, with 8095% efficacy after a 7-day course (Box
84-2). Its efficacy is considered to be related to inhibition of
attachment. Because of the disulfiram effect of metronidazole,
patients should be warned that concurrent use of ethanol could
cause flushing, tachycardia, and nausma. Tinidazole is also
considered a first-line agent with 90% efficacy, but it is also not
Adults
First
Choice
Second
Choice
Children
Metronidazole, 5 mg/kg
three times daily 7 d
OR
Furazolidone liquid, 6 mg/kg
divided 4/day for 10 d
Pregnancy
1 Not
Prognosis
The natural history of untreated giardiasis is unknown. Chronic
persistent diarrhea may develop in a small number of patients,
some of whom, particularly children, may develop malnutrition
and growth impairment. The prognosis of treated giardiasis,
however, is excellent.
Prevention
&
Control
Prophylactic
Measures
Isolation
Precautions
Good
hygiene
practices
REFERENCES
Abramowitz MD: Drugs for parasitic infections. Med Lett
Drugs Ther 1995;37:971.
Backer HD: Effect of heat on the sterilization of artificially
contaminated water. J Travel Med 1996;3:1.
Farthing MJG: Giardiasis. Gastroenterol Clin North Am
1996;25:493.
Hill DR: Giardia lamblia. In Mandell GL, Bennett JE, Dolin R:
Principles and Practice of Infectious Diseases, 3rd ed. Wiley,
1995.
Marshall MM et al: Waterborne protozoan pathogens. Clin
Microbiol Rev 1997;10:67.
Schwartz DA, Mixon JP, Owen RL: Giardiasis. In Connor DH,
Chandler FW: Pathology of Infectious Diseases. Appleton &
Lange, 1997.
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > A Protozoa > 85 - Leishmania & Trypanosoma
85
Leishmania
&
Trypanosoma
D. Scott Smith MD
David A. Relman MD
The genera Leishmania and Trypanosoma are members of the family
Trypanosomatidae. These protozoans cause diseases with widely
varied clinical presentations as well as geographic distributions,
including leishmaniasis, American trypanosomiasis (Chagas' disease),
and African trypanosomiasis (sleeping sickness). For example, the
endemic zones for African and American trypanosomiasis do not
overlap, the diseases are transmitted by different vectors, they
involve distinct mechanisms of pathogenesis, and they follow
different clinical courses. Nonetheless, the causative agents share
important biological features. Each is a hemoflagellate with a
kinetoplast containing its own chromosomal DNA with highly
conserved and repeated elements, each forms a single flagellum at
some point during its life cycle, and each is highly adapted to life
within an insect.
LEISHMANIA
Essentials
of
Diagnosis
General
Considerations
confirmation.
provides an
reservoirs to
reservoirs but only
for example, the
Clinical
Cutaneous
Findings
Leishmaniasis. Cutaneous leishmaniasis begins as
Leishmaniasis.
Mucocutaneous
leishmaniasis
involves the mucosal membranes of the nose and mouth but may
also involve the oropharynx and the larynx. L braziliensis is the
cause of most mucocutaneous disease. An estimated 3% of
patients with infection by this species develop mucosal disease.
The disease begins as a primary cutaneous ulcer at the site of
inoculation. During early stages it cannot be distinguished
clinically from the more benign cutaneous forms of disease. The
time delay from cutaneous disease to development of mucosal
involvement can vary from 1 month to 24 years. Mucosal disease
may present as nasal obstruction or epistaxis. A slight reddening
and swelling in the septum can be seen, which may progress to
perforation. Although the disease is termed mucocutaneous,
tracheal and genital mucosal involvement is rare.
Visceral
Diagnosis
The first step in diagnosis should be to establish an exposure history.
It is important to distinguish the more innocuous cutaneous forms of
leishmaniasis from the mucocutaneous forms, which are not usually
Fungal
Histoplasmosis
Sporotrichosis
Lobomycosis
Coccidioidomycosis
Blastomycosis
Chromomycosis
Histoplasmosis
Paracoccidiodomycosis
Rhinosporidiosis
Histoplasmosis
Viral
Orf
Infectious
mononucleosis
Protozoan
Drucunculiasis
Acute
Chagas'
disease
Schistosomiasis
Amebic liver abscess
Malaria
Other
(non-infectious)
Foreign-body
granuloma
Cutaneous
Mucocutaneous
Visceral
Treatment
The drugs of choice for leishmaniasis include the organic antimonial
compound stibogluconate sodium and meglumine antimoniate (Box
85-1 ). Anti-Leishmania drugs can be obtained from the CDC by
calling (404) 639-3670.
Several alternative regimens and therapies are used, because of
increasing resistance and treatment failures including higher dosing
and, in some instances, combination therapy to decrease the
duration of treatment. The newer drugs include liposomal
amphotericin B, pentamidine, as well as paromomicin, and cytokines
(eg, interferon gamma), which are used in combination with the
antimonials.
Cutaneous
Leishmaniasis. Cutaneous leishmaniasis is usually
self-limited, but, if it persists > 6 months or is disfiguring or
disabling, then treatment is indicated. The challenge for local
therapy is that the disease characteristically involves the dermis
Cutaneous
Meglumine antimonate (glucantime), 20 mg/kg/d IM or IV for 10
d
Stiboguconate, 20mg/kg/d IV or IM, preferably in two divided
doses for 10 d
Pentamadine, 24 mg/kg IM every other day 715
injections
Local treatment with intralesional injection of stibogluconate,
every other day 824 injections for nondisseminated
infections
Mucocutaneous
Stibogluconate, 20 mg/kg/d IVor IM, preferably in two divided
doses, 30 d
Visceral
Stibogluconate, 20 mg/kg/d IV or IM, preferably in two divided
doses, 30 d
If resistance: pentamidine, 4 mg/kg 3 times week for 5 weeks
OR
Amphotericin B, 1 mg/kg IV every other day 20 d
May reduce the course from 28 to 15 d by adding aminosidine
(paromomycin), 15 mg/kg/d IM
First
Choice
Comments
and
Alternatives
Prevention
&
Control
Measures
Precautions
None
BOX 85-2 Control of Leishmaniasis
TRYPANOSOMA
Three human pathogens are members of the genus Trypanosoma.
These are T cruzi , the agent of American trypanosomiasis (also
known as Chagas' disease), and T brucei subspecies rhodesiense and
gambiense , both of which cause African sleeping sickness. Both of
these diseases involve persistent circulation of parasites in the blood
during some part of the disease course; these organisms are
therefore referred to as hemoflagellates.
Trypanosomes have morphologically and physiologically different
developmental stages in their insect and mammalian hosts. Like
Leishmania spp., each stage contains a kinetoplast with highly
conserved and repeating DNA sequences. Aside from morphology, the
agents of African and American trypanosomiasis have little in
common. The endemic zones of disease do not overlap, the
organisms use different vectors, and their patterns of transmission
are distinct. Furthermore, the clinical courses and response to
therapy of these diseases are different.
AMERICAN
DISEASE)
Essentials
TRYPANOSOMIASIS
of
(CHAGAS'
Diagnosis
exam:
General
Considerations
Clinical
Findings
and right bundle branch block. Death can result from arrhythmia or
congestive heart failure. Sudden death occurs in 40% of congestive
heart failure patients with Chagas' disease. The second most
commonly affected organ system is the gastrointestinal tract. The
autonomic ganglia are destroyed, resulting in functional denervation,
impaired motility, and thus dilation, leading to megaesophagus and
megacolon.
Congenital Chagas' disease is characterized by hepatosplenomegaly,
sepsis, myocarditis, and hepatitis; however, two-thirds of cases of
congenital Chagas' disease are asymptomatic. Thus, routine testing
for disease in the infants of infected mothers is warranted.
Acute infection and
transplant recipients
severe clinical signs,
reactivation has led
Diagnosis
The diagnosis of acute Chagas' disease is made by detecting
parasites in the blood, by using a wet preparation of anticoagulated
blood or buffy coat or by using a Giemsa-stained smear of the blood.
P.849
Both enzyme immunoassay and ELISA tests are available
commercially and are approved by the US Food and Drug
Administration for the diagnosis of Chagas' disease. False-positive
results using these tests are an ongoing challenge, because there is
cross-reactivity among patients with syphilis, malaria, leishmaniasis,
and other parasitic diseases. PCR tests are also actively being
studied and evaluated, although they are not yet available for
routine clinical use. Serum samples can be sent to the CDC for
indirect immunofluorescence and complement fixation testing
(phone: [770] 488-4414).
Treatment
Acute American trypanosomiasis should be treated with nifurtimox
(Box 85-3 ). In the United States, this drug is available through the
Prevention
&
Control
Choice
Pediatric
Prophylactic
Measures
Precautions
None
BOX 85-4 Control of American Trypanosomiasis (Chagas'
Disease)
Travelers to endemic areas are advised to avoid sleeping in
structures that may harbor the insect vector and to use appropriate
barriers to avoid contact with the insects.
AFRICAN
TRYPANOSOMIASIS
Essentials
of
Diagnosis
periodic
fevers,
wasting,
nutritional
deficiencies.
posterior
cervical
lymphadenopathy.
indirect
immunofluorescence,
ELISA.
fluid
motile
(CSF):
lymphocytic
pleocytosis,
elevated
trypanosomes.
P.850
General
Considerations
Figure
from one VSG to another. This antigenic switching not only allows
evasion of the host's immune system but also poses a major
challenge to the development of a vaccine. Acquired immunity
does develop, but it is specific for a limited number of VSGs.
Resistance to African trypanosome infections depends on the
presence of host interferon gamma and a strong Th1 cytokine
response, as is the case for host resistance to Leishmania
infections. Humoral and cellular immune responses are directed
against the VSGs, among other trypanosomal components.
Clinical
Findings
First
Choice
Pediatric
Diagnosis
A Giemsa or Wright-stained smear of peripheral blood during the
acute febrile period is the best means of obtaining a diagnosis
(Figure 85-4 ). T brucei rhodesiense tends to have higher parasite
loads and may be easier to detect than T brucei gambiense , which
may require more frequent repeated blood smears or use of
concentration techniques, eg, microhematocrit centrifugation with
examination of the buffy coat. If a chancre is present, aspiration and
staining may yield a diagnosis before parasitemia is present.
Organisms may be demonstrated from aspirates of lymph nodes and
bone marrow. The CSF should be examined even if parasitemia is
confirmed. This should be done after clearance of the parasites from
the blood so that parasites are not introduced into the CSF. In CNS
trypanosomal infection, the CSF reveals a lymphocytic pleocytosis,
elevated protein, and sometimes motile trypanosomes. Often morular
or so-called Mott cells are seen, which are plasma cells with large
eosinophilic inclusions containing immunoglobulin G. Several
immunodiagnostic tests are available including indirect
immunofluorescence, ELISA, and a card agglutination test that uses a
commonly occurring variant antigen.
Treatment
The two forms of African sleeping sickness can be treated in a similar
fashion. Eflornithine (difluoromethyl-ornithine) inhibits ornithine
decarboxylase, an essential parasite enzyme, and is an effective drug
in both the early and later CNS stages of disease (Box 85-5 ). The
side effects include vomiting, abdominal pain, and diarrhea. Seizures
occur in < 5% of cases. Unfortunately, there is a current shortfall in
drug supply, with no signs of immediate improvement. Suramin has
also been shown to be effective. It is available in the United States
only through the CDC. The urine should be checked prior to each
dose for protein, and the dose or interval between doses should be
altered if the specimen is positive. Pentamidine has been used as an
alternative agent, but it is not US Food and Drug Adminstrationapproved for this indication. Drug information is available through
Measures
not
available
Precautions
None
BOX 85-6 Control of African Trypanosomiasis
African sleeping sickness tends to relapse, even after appropriate
therapy; in this event, treatment should be repeated. Because
parasitic confirmation of relapse may not be possible, increasing CSF
protein or pleocytosis may be used as a marker of relapse. Infection
does not confer immunity, and reinfection presents as new infection,
often with chancres. Despite treatment, this disease is fatal in ~ 7%
of patients.
Prevention
&
Control
REFERENCES
(Chagas'
disease).
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > B Helminths > 86 - Nematodes
86
Nematodes
James M. Steckelberg MD
Walter R. Wilson MD
Essentials
of
Diagnosis
Intestinal nematodes:
or parasites in stool.
demonstration
of
characteristic
eggs
General
Considerations
INTESTINAL
NEMATODE
INFECTIONS
ASCARIASIS
Worldwide, more than 1 billion people are infested with Ascaris
lumbricoides , the causative agent of ascariasis or roundworm.
More than 4 million people are estimated to be infected in the
United States. Infection occurs predominately in the
southeastern states and more commonly in younger children,
and it is associated with lower socioeconomic status. The
organism is acquired through ingestion of embryonic forms of
the worm, which are found in fecally contaminated soil. After
ingestion, the embryonic eggs hatch in the small intestine, and
the larvae undergo a tissue migration phase. During the
migration, the larvae penetrate the intestinal wall and travel
intravenously to the pulmonary alveoli. In the lungs, the
organisms provoke a cough, are swallowed by the host, and
subsequently mature into the adult worm in the small intestine.
A single adult female ascarid may produce 200,000 ova daily,
which are shed in the feces.
Clinical
Findings
Differential
Diagnosis
Treatment
All patients with ascariasis should be treated, even if
asymptomatic, to prevent biliary migration and obstruction (Box
86-2 ). Ascarids should be treated first in mixed parasitic
infections, and they should be treated before general anesthesia
because of the risk
P.856
of inducing migration of hypermotile worms. In some cases,
endoscopic removal of worms may be indicated. Stools should
be reexamined 2 weeks after therapy and treatment repeated as
necessary.
Intestinal
Ascaris
lumbricoides
Ancylostoma
braziliense or A. caninum (dog and cat
intestinal hookworms; cutaneous larva migrans in humans)
Enterobius
vermicularis (pinworm)
Ancylostoma duodenale (Old World), Necator
americanus (New World) (hookworms)
Strongyloides
stercoralis
Trichuris trichiura (whipworm)
Capillaria
philippinensis (intestinal capillariasis)
Trichostrongylus spp.
Anisakiasis (larval fish nematode)
Tissue dwelling
Filariasis
tissue
nematodes
Dracunculus
medinensis (Guinea worm)
Trichinella
spiralis
Toxocara spp. (larval stagesvisceral larva migrans)
Angiostrongylus
cantonensis (meningitis)
1
Prognosis
Prognosis is generally excellent, although reinfection is possible.
In rare cases, obstruction of the small intestine by a mass of
worms may cause an acute abdominal syndrome. In addition,
obstruction of the common bile duct may cause acute biliary
colic.
Prevention
Roundworm infection can be prevented by avoiding ingestion of
fecally contaminated soil. Measures to accomplish this include
hygienic disposal of fecal waste, avoidance of the use of night
soil and proper washing of foods contaminated by soil, hand
washing, and avoidance of pica.
ENTEROBIASIS
Also known as pinworm, infection by Enterobius
vermicularis is
the most common helminth infection in the United States.
Clinical
&
Laboratory
Findings
Differential
Diagnosis
Treatment
Treatment suggestions are given in Box 86-2 .
Prognosis
Prognosis is excellent, although reinfection is common in the
setting of continued exposure.
Prevention
Reinfection is common in households with an infected person;
examination for asymptomatic carriers and simultaneous
treatment of all infected household members may be required.
Household members should practice hand washing before meals
and after defecation and should launder bedding and bedclothes
to eliminate environmental eggs.
ANCYLOSTOMIASIS
&
NECATORIASIS
Enterobiasis
Pyrantel pamoate, 1011 mg/kg once
Mebendazole, 100 mg once, repeat in 2 wk
Albendazole, 400 mg once, repeat in 2 weeks
Pyvinium pamoate, 5 mg/kg once, repeat in 2 weeks
Hookworm
Pyrantel pamoate, 1011 mg/kg once daily for 3 d
Mebendazole, 100 mg twice daily for 3 d
Albendazole, 400 mg once (Ancylostoma1 ) or once daily for
3 d (Necator1 )
Strongyloidiasis
Albendazole, 400 mg/d once or twice daily for 37 d, may
repeat in1 wk
Ivermectin, 200 g/kg once daily for 2 d
Thiabendazole, 25 mg/kg twice daily for 3 d; continue for
57 d in disseminated infection
Trichuriasis
Albendazole, 600 mg once
Mebendazole, 100 mg twice daily for 3 d
Oxantel pamoate, 15 mg/kg once
1
Choice
Second
Choice
Clinical
&
Laboratory
Findings
Differential
Diagnosis
Treatment
Re-treatment at 2-wk intervals may be necessary to reduce the
worm burden to low levels (see Box 86-2 ). Because light
infections are usually asymptomatic, complete eradication may
not be therapeutically necessary. In patients with iron
deficiency, supplemental iron therapy (eg, ferrous sulfate, 200
mg 3 times daily for several months, followed by 200 mg daily
until iron stores are repleted) may be necessary.
Prognosis
Prognosis with treatment is excellent.
STRONGYLOIDIASIS
Infection by S stercoralis (threadworm) is especially notable
because the worm is parthenogenetic and larvae mature to an
Clinical
&
Laboratory
Findings
Many patients with chronic but low worm burden infections are
asymptomatic or have irregular intestinal symptoms. During
initial skin penetration, local skin irritation, pruritic dermatitis,
urticaria, and serpiginous tracts (larva currens) may be
seen. During pulmonary migration, symptoms and signs of
infection are similar to those of other nematodes that travel
through the lung; that is, dry cough, wheezing, low-grade fever,
dyspnea, and hemoptysis. Symptoms of chronic intestinal
infestation are varied and nonspecific, and they may include
bloating, abdominal distension, dyspepsia, epigastric pain,
pruritus ani, diarrhea, and flatulence. In immunocompromised
patients, hyperinfection syndrome may be manifested by
gastrointestinal ulceration, peritonitis, ileus, biliary obstruction,
cholecystitis, or hepatic granulomas. Invasion of extraintestinal
organs, including meningitis, central nervous system invasion,
pericarditis or myocarditis, or pleuritis, may also occur. Gram-
Differential
Diagnosis
fistula.
Treatment
Eradication is the goal of therapy (see Box 86-2 ). When
immunosuppression can be anticipated, such as in patients
being evaluated for organ transplantation, screening for S
stercoralis and eradication should occur before
immunosuppression.
Prognosis
In immunocompetent hosts, prognosis is good. Severe infection
with multiple complications may occur in immunocompromised
hosts with hyperinfection syndrome.
TRICHURIASIS
Trichuriasis or whipworm is caused by Trichuris trichiura. These
small (30- to 50-mmlength) whiplike nematodes attach to
the mucosa of the large intestine, especially the cecum; there is
no extraintestinal phase. Infection occurs by ingestion of
infective eggs from soil contaminated with feces; 24 wk of
maturation in soil are required for the larvae within the eggs to
become infective; thus, direct person-to-person transmission
does not occur.
Clinical
&
Laboratory
Findings
Treatment
Treatment of symptomatic trichuriasis is outlined in Box 86-2 .
Prognosis
Prognosis
is
TISSUE
excellent.
NEMATODE
LYMPHATIC
INFECTIONS
FILARIASIS
Clinical
&
Laboratory
Findings
Treatment
Symptomatic treatment of acute filarial lymphangitis (eg,
antihistamines and aspirin) may be helpful in reducing the
intensity of symptoms. DEC is an effective microfilaricidal drug,
but the adult worms require a longer course of therapy and
sometimes multiple courses of therapy to be eradicated. DEC (2
mg/kg) is administered 3 times daily for 23 wk. Allergic
reactions (eg, fever, urticaria, or lymphangitis) to injured
parasites may occur early in therapy; some authorities suggest
smaller doses of DEC (50 mg on the first day, increasing to full
dosage over 34 d) to minimize these reactions.
Antihistamines may also be of benefit. Nonspecific side effects
include headache, vertigo or dizziness, malaise, fever, or
myalgias. Onchocerciasis should be excluded before DEC
treatment. DEC is available in the United States from Lederle
Laboratories
(800-934-5556).
Prevention
Because transmission depends on mosquito vectors, control
measures are directed at reducing mosquito populations and
OTHER
1.
FILARIAL
INFECTIONS
LOIASIS
Clinical
Findings
Treatment
Treatment is with DEC, 3 mg/kg 3 times daily for 21 d.
Localized inflammatory reactions to dying adult worms in tissues
2.
ONCHOCERCIASIS
Clinical
Findings
Treatment
The treatment of choice is ivermectin, 150 5g/kg orally as a
single dose, which kills microfilariae but is less effective against
adult worms. Treatment is repeated at 3-mo intervals for 23
years. Diethylcarbamazine has been used historically but is less
effective and more toxic than ivermectin, and it is no longer
recommended by the World Health Organization. Cutaneous
nodules, especially on the scalp, may be surgically excised.
OTHER TISSUE
INFECTIONS
1.
NEMATODE
TRICHINOSIS
Clinical
&
Laboratory
Findings
Treatment
Treatment for trichinosis remains controversial and is primarily
supportive. If ingestion is known to occur within 24 h,
albendazole (400 mg twice daily, (60 days), mebendazole
(200400 mg 3 times daily for 3 days, then 400500 mg 3
times daily for 10 days), or thiabendazole (25 mg/kg/day for 1
wk) has been proposed to prevent infection. The drug is not
beneficial for established infection or muscle larvae. No specific
therapy has been unequivocally demonstrated to be of benefit
during the muscle invasion stage.
Prognosis
Spontaneous recovery is the rule, although full recovery may
require weeks to months. Death, typically from myocarditis,
encephalitis, or pneumonitis, is rare.
P.861
Prevention
The incidence of human trichinosis has declined in developed
countries with measures designed to reduce the prevalence of
trichinosis in hogs. Trichina in wild game (or pork) can be killed
by thorough cooking (internal temperature > 62C) throughout
all parts of the meat or to > 56C for > 15 min, freezing < -
3. TOXOCARIASIS
MIGRANS)
(VISCERAL
LARVA
the bitch.
shed copious
become
to harsh
Clinical
&
Laboratory
Findings
Treatment
No specific therapy has been proven effective. In many cases,
Prevention
&
Prognosis
4.
DRACUNCULIASIS
Clinical
Findings
Treatment
No specific antihelminthic therapy is available to kill adult
worms. Mechanical removal of worms has been practiced for
centuries. General treatment is focused on controlling
complications, including bed rest, elevation of the affected
extremity, wound care, and antibacterial therapy for secondary
bacterial wound infections. Metronidazole, 250 mg orally 3 times
daily, mebendazole, 400800 mg orally daily, or
thiabendazole 25 mg/kg twice daily may be helpful in promoting
the expulsion of the worm, as is immersion of the affected limb
in water several times daily.
Prevention
Noncontaminated drinking water is
dracunculiasis. The World Health
program has focused on provision
using tube wells, hand pumps, or
water supplies with temephos (to
REFERENCES
Markell EK et al: Medical
Saunders, 1992.
Strickland
GT
(editor): Hunters
Tropical
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > B Helminths > 87 - Cestodes
87
Cestodes
Andrew D. Badley MD
James M. Steckelberg MD
Walter R. Wilson MD
Human infections caused by cestodes, or tapeworms, may occur
within the lumen of the bowel, where adult cestodes attach
themselves to the host intestine (Box 87-1). Alternatively, human
infection may be the result of dissemination of cestodes from the
bowel to involve extraintestinal sites, often by larval forms of the
parasite. The life cycle of cestodes is determined by definitive
hosts, in whom the mature adult worm lives, and intermediate
hosts, which harbor the larval forms of the parasite. Humans are a
definitive host for six cestodes: Diphyllobothrium latum, Taenia
solium, Taenia saginata, Hymenolepis diminuta, Hymenolepis
nana, and Dipylidium caninum. In addition, humans may be
intermediate hosts for Echinococcus
granulosis and Echinococcus
multilocularis. All forms of disease associated with infections
caused by cestodes are treatable; therefore, a careful history and
physical examination to identify potential patients is warranted.
Cestodes attach themselves to the intestinal mucosa by means of
a specialized organ called the scolex, which has a distinctive
morphology for each species of cestode. Attached to the scolex are
DIPHYLLOBOTHRIUM
INFECTION
Essentials
of
LATUM
Diagnosis
proglottid
General
contains
rosette-shaped
central
uterus.
Considerations
Clinical
Findings
Differential
Diagnosis
BOX 87-1
Syndrome
Diphyllobothrium
latum infection
More
Common
Less
Common
Bloating,
abdominal
Intestinal
obstruction,
pain,
B 12
diarrhea
vitamin
deficiency
Taenia solium
infection
Asymptomatic
Indigestion,
nausea
Cysticercosis
(extraintestinal
T solium
infection)
Headache,
seizures,
neurologic
deficits
Myositis, liver or
heart failure
Taenia saginata
infection
Asymptomatic
Abdominal
malaise
Hymenolepis
nana infection
Abdominal
pain
Dizziness,
anorexia;
childrenbehavioral
disturbance
Hymenolepis
Asymptomatic
cramps,
diminuata
infection
Dypylidium
Asymptomatic
caninum
infection
Echinococcal
infection
Indigestion,
anorexia,
pruritis
Abdominal
pain, mass
anal
Seizures,
headache,
neurologic
deficits,
bone pain
Complications
The complications vary with the clinical syndrome associated with
infection. Chronic diarrhea may lead to malnutrition. Megaloblastic
anemia secondary to B12 deficiency results when the parasite
disrupts the B12-intrinsic factor complex, resulting in B12 becoming
unavailable for absorption by the host. B12 deficiency may lead to
neurologic sequelae including peripheral neuropathy, dementia,
and possible severe combined degeneration of the posterior
columns. Also, infection with D latum may rarely result in
intestinal obstruction caused by a mass of entangled worms.
Treatment
Therapy for infection with D latum consists of either praziquantel
or niclosamide (Box 87-2). Follow-up examinations of stool should
be performed 1 and 3 months after treatment.
Prognosis
Since the disease is not commonly associated with severe
symptoms, the prognosis of infected individuals is excellent. One
exception is with patients who manifest B12 deficiency, in whom
the neurologic complications are reversible only if recognized and
treated early.
Prevention
&
Control
TAENIA
Essentials
Spheroidal
SOLIUM
of
INFECTION
Diagnosis
yellow-brown
eggs
(3143
m).
General
Considerations
BOX 87-2
Syndrome
Adult
treatment
Pediatric
treatment
Diphyllobothrium
Praziquantel,
Praziquantel,
latum infection
1020
mg/kg once
OR
Niclosamide 2
g once
1020
mg/kg once
OR
Niclosamide
(1134
kg), 1 g
once; (>34
kg), 1.5 g
once
Taenia solium
infection
Cysticercosis
(extraintestinal
T solium
infection)
Praziquantel,
1020
mg/kg once
OR
Praziquantel,
1020
mg/kg once
OR
Niclosamide,
2 g once
Niclosamide
(1134
kg), 1 g
once; (>34
kg), 1.5 g
once
Surgery and
either
Praziquantel,
20 mg/kg
three times
daily
1530 d
Surgery and
either
Praziquantel, 20
mg/kg three
times daily
1530 d
OR
OR
Albendazole,
7.5 mg/kg
three times
daily 8 d
Taenia saginata
infection
Albendazole,
7.5 mg/kg
three times
daily 8 d
Praziquantel,
1020
Praziquantel,
1020
mg/kg once
OR
Niclosamide,
2 g once
mg/kg once
OR
Niclosamide
(1134
kg), 1 gm
once; (>34
kg), 1.5 g
once
Hymenolepis
Praziquantel,
Praziquantel,
nana infection
1020
mg/kg once
OR
Niclosamide,
1020
mg/kg once
OR
Niclosamide
2 g once
(1134
kg), 1 gm
once; (>34
kg), 1.5 g
once
Hymenolepis
diminuta
infection
Niclosamide,
2 g once
Niclosamide
(1134
kg), 1 g
once; (>34
kg), 1.5 g
once
Dypylidium
Niclosamide,
Niclosamide
caninum
infection
2 g once
(1134
kg), 1 g
once; (>34
kg), 1.5 g
once
Echinococal
infection
Clinical
Surgery and
albendazole,
Surgery and
albendazole,
400 mg
divided into 2
daily doses
3 mo
OR
15 mg/kg/d
divided into 2
daily doses
3 mo
OR
Mebendazole,
50 mg/kg/d
divided into 3
daily doses
Mebendazole,
50 mg/kg/d
divided into 3
daily doses
3 mo
3 mo
Findings
including
indigestion
and
Laboratory
Findings. Patients with intestinal T solium
infection will frequently have abnormal results of stool
examinations for ova and parasites and occasionally will have
a mild leukocytosis with eosinophilia.
BOX 87-3
Syndrome
Preventative
Measures
Diphyllobothrium
latum infection
Taenia
solium infection
pork
products
Cysticercosis
(extraintestinal T
solium infection)
As for T solium
Taenia saginata
infection
Hymenolepis
infection
nana
Hymenolepis
infection
diminuta
Dypylidium
infection
Echinococcal
caninum
infection
Differential
Diagnosis
Complications
T solium infection of the intestine is not commonly associated with
symptoms; however, in patients with high parasite loads,
obstruction may occur.
Treatment
Therapy for T solium infection of the intestine consists of either
praziquantel or niclosamide (see Box 87-2). Follow-up
examinations of stool should be performed 1 month after
treatment.
Prognosis
The prognosis for patients with intestinal T solium infection is
excellent.
Prevention
&
Control
CYSTICERCOSIS
(CYSTICERCUS
CELLULOSEA INFECTION)
Essentials
of
Diagnosis
aspiration
of
cysts
(characteristic
cytomorphology).
General
Considerations
Clinical
Findings
P.867
that occurs in response to the larva. Within the brain,
cysticercosis may cause arachnoiditis or chronic meningitis,
with associated headache, vertigo, vomiting, and cranial
neuropathies. Alternate presentations include obstructive
hydrocephalus with ataxia and dementia, intracranial vasculitis
with focal neurologic signs and neuropsychiatric changes, or
mass effect with seizures, headache, or focal neurologic
deficits. In addition, cord compression with lower limb
weakness and loss of bowel and bladder continence may occur.
Cysts outside the central nervous system tend to occur within
muscle, are most often asymptomatic, and eventually die,
calcify, and may be incidentally detected on radiographs.
Occasionally, muscle cysts will cause pseudohypertrophy that
may be associated with myositis, high fever, and eosinophilia.
Cysts may also occur within critical organs (commonly heart
and liver) where they present as mass lesions with pain or
obstructive
symptoms.
Laboratory
Differential
Diagnosis
Complications
Visceral cysticercosis is also commonly asymptomatic, but may
obstruct local structures (eg, biliary obstruction in hepatic
cysticercosis). Neurocysticercosis may lead to
neurologic impairment, coma, or even death.
permanent
Treatment
Therapy for cysticercosis includes surgery when feasible and
necessary, in combination with praziquantel or albendazole (see
Box 87-2). Therapy of cysticercosis commonly increases the local
inflammation, thereby transiently causing a paradoxical worsening
of the patient's symptoms. Whether corticosteroids should be used
as adjunctive therapy for patients being treated for
neurocysticercosis remains in debate.
Prognosis
The mortality rate for untreated neurocysticercosis approaches
50%, but treatment decreases this rate to 515%.
Prevention
&
Control
TAENIA
Essentials
SAGINATA
of
Stool examination
(3143 mm).
INFECTION
Diagnosis
reveals
spheroidal
yellow-brown
eggs
General
Considerations
Clinical
Findings
Differential
Diagnosis
Complications
Usually no complications are associated with T saginata; however,
regurgitation and aspiration of proglottids may occur.
Treatment
Therapy for infection with T saginata is similar to treatment of
intestinal T solium, a single dose of either praziquantel or
niclosamide (see Box 87-2). Follow-up examinations of stool
Prognosis
The prognosis for patients with intestinal T saginata infection is
excellent.
Prevention
&
Control
HYMENOLEPIS
Essentials
of
NANA
INFECTION
Diagnosis
General
Considerations
Clinical
Findings
Differential
Diagnosis
Complications
Through a mechanism that is still unclear, seizures have been
reported with H nana infections.
Treatment
Cysts of H nana are more resistant to therapy than adult worms.
Therefore higher doses or longer courses of therapy are required
to eradicate cysts than with other cestode infections. Therapy for
infection by H nana consists of a single dose of either praziquantel
or niclosamide (see Box 87-2). Follow-up examinations of stool
should be performed at 2 weeks and 3 months after therapy.
P.869
Prognosis
Since infection with H nana is usually asymptomatic and infection
responds to therapy, the prognosis is excellent.
Prevention
&
Control
HYMENOLEPIS
Essentials
of
DIMINUTA
Diagnosis
General
Considerations
Clinical
Findings
Differential
Diagnosis
Complications
No complications have been reported.
Treatment
Therapy for infection for H diminuta consists of niclosamide in a
one-time dose (see Box 87-2) .
Prognosis
H diminuta responds promptly to therapy, so the prognosis is
excellent.
Prevention
&
Control
DIPYLIDIUM
Essentials
of
CANINUM
INFECTION
Diagnosis
General
Considerations
Clinical
Findings
Laboratory
Findings. Microscopic stool examination will
frequently reveal characteristic egg clusters and proglottids.
As with other cestode infections, blood examination may
demonstrate
mild
Differential
leukocytosis
with
eosinophilia.
Diagnosis
Complications
No complications are associated with D caninum
infection.
Treatment
Therapy for D caninum infection is niclosamide in a one-time dose
(see Box 87-2) .
P.870
Prognosis
The prognosis for D caninum infections is excellent.
Prevention
&
Control
ECHINOCOCCAL
INFECTION
Essentials
of
Diagnosis
echinococcal
serology
General
Considerations
Clinical
Findings
Differential
Diagnosis
obstruction, or
primary differential
malignancy of each
the radiographic
Complications
On occasion, hydatid cysts may leak fluid into the systemic
circulation of the host, causing sensitization of the host.
Subsequent fluid leaks may then be responsible for the induction
of an allergic response or even anaphylaxis. In addition, release of
cyst tissue may be associated with embolization and the
development of additional cysts at distant alternate sites. Cysts
also may become secondarily infected, producing abscesses.
Treatment
Therapy for hydatid cysts caused by infection with E
combines surgical and pharmacological interventions
granulosus
(see Box 87-
Prognosis
The prognosis of hydatid disease is variable. With early diagnosis
and treatment of simple unilocular cysts, the outlook is excellent;
in contrast, advanced multilocular disease at multiple sites with
advanced portal hypertension is a potentially lethal condition.
Medical therapy of inoperable E granulosus cysts is associated with
cure in 30% of cases and improvement in 50%. Inoperable E
multilocularis is associated with a 10-year mortality rate in 90% of
cases. In such cases, indefinite treatment with albendazole or
mebendazole is recommended by some authorities.
Prevention
&
Control
REFERENCES
Garcia LS, Bruckner DA (editors): Diagnostic
Parasitology, 3rd ed. ASM Press, 1997.
Strickland
Saunders,
GT (editor): Hunters
1991.
Tropical
Medical
2001
McGraw-Hill
> Table of Contents > Section VII - Parasitic Infections > B Helminths > 88 - Trematodes
88
Trematodes
Walter R. Wilson MD
James M. Steckelberg MD
Essentials
of
Diagnosis
(Table 88-1 ).
CLINICAL
SYNDROMES
Considerations
The final habitat for blood flukes is the venous system of the bowel
mesentery or the urinary bladder.
Epidemiology. It is estimated that schistosomiasis occurs in >
200 million people worldwide and is endemic
America, and other parts of the world where
engaged in freshwater agriculture. The total
individuals in the United States is estimated
Clinical
Findings
The three different stages (cercariae, mature flukes, and eggs) of the
blood fluke in humans result in three major disease syndromes in
chronologic order: dermatitis (swimmers' itch), fever and
constitutional complaints (Katayama fever), and finally chronic fibroobstructive disease (Box 88-1 ).
Signs and Symptoms. Dermatitis (swimmers' itch) is the acute
form of schistosomiasis and is characterized by a pruritic and
papular rash that usually occurs within 13 days after
penetration of the cercariae. Swimmers' itch rarely occurs after
primary
P.873
exposure and is more common in individuals who have been
sensitized by earlier exposure.
Blood
Schistosomiasis
S mansoni
S japonicum
S haematobium
S mekongi
S intercalatum
Snails
Snails
Snails
Snails
Snails
None
None
None
None
None
Inferior
mesenteric
veins
Small bowel
Lung
Paragonimiasis
P westermani
Snails
Crabs and crayfish
Lungs
Intermediate
Type
Infection
Species
Primary
Host
Secondary
Site
Parasitic
in
Humans
Blood flukes
S mansoni
S japonicum
S makongi
S intercalatum
S haematobium
Pulmonary schistosomiasis,
with seizures
Transverse
myelitis
Liver
central
nervous
flukes
C sinensis
D felineus
F hepatica
Most patients have no symptoms
Early stageRight upper quadrant pain,
hepatomegaly,
eosinophilia
Biliary
obstruction,
cholangitis
Intestinal flukes
F buski
Most patients have no symptoms
Abdominal
Lung
flukes
pain,
diarrhea,
malabsorption
system
involvement
westermani
Many patients have not symptoms
Cough productive brown sputum, hemoptysis,
Chronic
bronchitis,
Trematode
More
bronshiectasis,
Common
Less
lung
eosinophilia
abscess
Common
S mansoni
Praziquantel, 20 mg/kg twice daily 1 day
Oxamniquine, 15 mg/kg single dose. Africanacquired infection, 20
mg/kg daily 3 days
S haematobium
Praziquantel, 20 mg/kg twice daily 1 day
Metrifonate, 7.5 mg/kg single dose, weekly 2 weeks
S intercalatum
Praziquantel, 20 mg/kg twice daily 1 day
No satisfactory alternative
S japonicum S mekongi
therapy
alternative
therapy
alternative
therapy
No satisfactory
F buski
P westermani
alternative
therapy
satisfactory
Species
alternative
First
Choice
therapy
Second
Choice
Differential
Diagnosis
Treatment
The treatment for patients with schistosomiasis is shown in Box 88-2
. Praziquantel is
schistosoma that
after treatment,
obtained several
Prognosis
The prognosis of schistosomiasis is excellent among patients who are
treated before end-stage hepatic or renal disease develops. In these
patients, prognosis depends on the magnitude of end-organ disease.
Prevention
The only effective means of prevention is to avoid contact with fresh
&
Considerations
The final common habitat for the liver flukes is the bile ducts. The
liver flukes that are the most common cause of human infections are
Clonorchis
sinensis (clonorchiasis), Opisthorchis spp.
(opisthorchiasis),
and Fasciola hepatica (fascioliasis).
C sinensis (Chinese or oriental liver fluke) is a flat, elongated fluke (~
15 mm (3 mm) that inhabits the distal biliary capillaries. Humans are
incidental hosts, and the infection is endemic in China, Hong Kong,
Korea, and Southeast Asia. Eggs eliminated in the feces are then
ingested by the specific snail intermediate host. After ingestion, the
eggs hatch into miracidia. The organisms multiply
extremely high numbers of cercariae that exit the
the skin of freshwater fish. Once the cercariae are
they encyst as metacercariae, which are infective
and produce
snail and penetrate
on the fish skin,
for humans.
h. The cercariae emerge from snails and encyst on aquatic plants and
sometimes in soil. The plants are consumed by humans, sheep, or
cattle. The organisms excyst in the duodenum. The larvae penetrate
through the intestinal wall into the peritoneum, enter through the
capsule of the liver, and migrate to the bile ducts.
Clinical
Findings
Differential
Diagnosis
Treatment
Praziquantel is effective therapy for symptomatic patients with C
sinensis or O felineus infection. Bithionol is the drug of choice for F
hepatica infection (Box 88-2 ).
Prognosis
The prognosis for treated patients with liver fluke infection is
excellent.
Prevention
Avoiding consumption of raw or undercooked freshwater fish is the
only effective means of prevention of C sinensis or O felineus
infection. Individuals should avoid consumption of undercooked
aquatic plants and grasses in areas where F hepatica is endemic.
P.876
Considerations
Clinical
&
Laboratory
Findings
Differential
Diagnosis
Treatment
Praziquantel is effective therapy for intestinal flukes (Box 88-2 ).
Prognosis
The Prognosis is excellent.
Prevention
Individuals residing in endemic areas should avoid consumption of
undercooked aquatic plants and grasses.
Considerations
Paragonimus
westermani is endemic in the Far East Indian
subcontinent, Central and South America, and West Africa. Human
lung flukes produce eggs in sputum that are swallowed, excreted in
the feces, and mature in fresh water into miracidia, which penetrate
snails. The mature cercariae exit the snail, penetrate into freshwater
crayfish and crabs, and encyst. Infection in humans occurs after
ingestion of raw, undercooked, or pickled freshwater crustacea. After
ingestion, the organisms excyst in the duodenum, penetrate through
the bowel wall, enter the peritoneal cavity, pass through the
diaphragm into the pleural space, and enter the lungs where they
mature into flukes that measure 715 mm (58 mm. Ectopic eggs
in the brain may result in space-occupying lesions and focal seizures.
Clinical
Findings
Differential
Diagnosis
Treatment
Praziquantel is effective therapy (Box 88-2 ).
Prognosis
The prognosis is excellent in patients who are treated before the
development of chronic bronchitis or bronchiectasis.
Prevention
Individuals should avoid the consumption of raw or undercooked
freshwater crustacea from areas where P westermani is endemic.
REFERENCES
Mahmoud AAF: Trematodes (schistosomiasis) and other flukes. In
Mandel GL et al: Principles and Practices of Infectious Diseases ,
4th ed. Churchill Livingstone, 1995.
Mahmoud AAF, Abdel Wahab MF: Tropical
, 2nd ed. McGraw-Hill, 1990.
and
Geographic
Medicine
2001
McGraw-Hill
89
Infections
in
Travelers
DeVon C. Hale MD
Caroline Milne MD
Essentials
of
Diagnosis
Fever
Weight loss
Diarrhea
Myalgia
Headache
Skin rash
General
Considerations
International travel has become a normal part of life. Physicians who are
knowledgeable regarding common infections encountered in international
travel and ways to prevent infection can provide a great service to their
patients.
Most travelers will not encounter tropical disease; a study of >
PRETRAVEL
EVALUATION
(Table 89-1 ).
Tape
Syringes
Needles
Scissors
Tweezers
Pain relievers (acetaminophen,
Cough suppressants
ibuprofen)
Decongestants
Antihistimines
Antacids
Antidiarrheal
agents
Topical antibiotics
Anti-itch lotions
Sunscreen
(calamine)
Medications
Routine
Immunization
Recommendations
Killed Virus
Data on safety in pregnancy are not available. Should weigh the
theoretical risk of vaccination against the risk of disease
Hepatitis B
Recominant produced, purified hepatitis B surface antigen
Pregnancy is not a contraindication
Influenza
Inactivated type A and type B virus vaccines
Usually recommended only for patients with serious underlying
disease. Consult health authorities for current recommendations
Japanese
Encephalitis
Killed virus
Should reflect actual risks of disease and probable benefits of vaccine
Poliomyelitis
Disease
Vaccination
Table
Vaccine
Type
Supplementary
1
Give dose 4 to children 46 years of age
Additional
1
Give a dose, once, to persons traveling to developing countries
Doses
Table
Other
Number of Doses
Comments
Recommended
Vaccinations
series
As indicated by manufacturer
Give doses 1 and 2 48 wk apart; give dose 3 612 mo after
dose 2
Booster
1
Give dose 4 to children 46 years of age
Additional
1
Give a dose, once, to persons traveling to developing countries
Doses
Table
Number of Doses
Dose
Volume
Comments
Rarely
Indicated
Vaccinations
Booster
PRP-OMP
Dose 1
Dose 2
Booster
PRP-D1
Single dose
1 PRP-D is recommended only for children 15 months of age.
Vaccine
Table
2
months
4
months
6
months
12
months
15
months
the CNS (see also Chapter 7 ). The illness may present as a febrile
headache, meningitis, or encephalitis. Transmission occurs from the
bite of the mosquito Culex
tritaeniorhynchus , which is the major
vector species. Risk of acquiring Japanese encephalitis virus is low
and of exhibiting clinical manifestations of disease is lower; only
1:300
seroconverters
develop
encephalitis.
10
Children and adolescents 1119 y old
5.0
10
Adults 20 y old
10.0
20
Dialysis patients and other immunocompromised persons
40.03
4 04
1 HBsAG, Hepatitis B surface antigen.
2 Both vaccines are routinely administered in a three-dose series.
Engerix-B also has been licensed for a four-dose series administered
at 0, 1, 2, and 12 months.
3 Special formulation (40 g in 1.0 mL).
4 Two 1.0-mL doses given at one site, in a fourdose schedule at 0,
1, 2, 6 months.
Dose (g)
Group1
Recombivax
Table
HB2
EngerixB2
and
adolescents4
218
720
0.5
2
0, 612
Adults
> 18
1400
1.0
2
0, 612
1 Hepatitis A vaccine, inactivated, SmithKline Beecham Biologicals.
2
Table
Age
Dose
Volume
No.
Schedule
(Years)
(EL.U.)2
(mL)
Doses
(Months)3
should be taken.
Three typhoid vaccines are available in the United States, an oral
live-attenuated vaccine, a parenteral heat-phenolinactivated
vaccine, and a capsular polysaccharide vaccine. The parenteral heatphenolinactivated vaccine is an older vaccine, has more
associated side effects, and is no longer commonly used. The
vaccines have comparable efficacy rates. See Table
and schedules.
adolescents
Adults
> 17
50
1.0
2
56
1 Hepatitis A vaccine, inactivated, Merck & Company, Inc.
2
Units
0 months represents timing of the initial dose; subsequent numbers
represent months after the initial dose.
3
Group
Table
Age
(Years)
Dose
(U)2
Volume
(mL)
No.
doses
Schedule
(months)3
2345
>45
0.5
1.0
2.0
Dose volume depends on body
weight and length of stay
Long-term travel (35 mo)
<22
<50
50100
>100
<10
<23
2345
>45
0.5
1.0
2.5
5.0
1
Kg = ~ 2.2 lbs.
2 For intramuscular injection.
Body
Weight
Length of
Stay
Table
Dose
lb
k g1
Volume2
(ml)
Comments
risk and the low benefit, cholera vaccine is indicated only for highrisk people working and living in endemic areas and in poor sanitary
conditions. Endemic areas are present in South and Central America,
Africa, and Asia. The vaccine is given as two subcutaneous,
intradermal, or intramuscular doses at least 1 week apart. An
additional booster dose is required every 6 months. See Table 89-15
for dosing recommendations.
Meningococcal
Meningitis. Neisseria
meningitidis causes a bacterial
meningitis that is responsible for multiple epidemics of disease (see
also Chapters 7 and 5 2 ). Epidemic areas include sub-Saharan Africa
during the dry season (DecemberJune). This area is know as the
meningitis belt. Recent epidemics have also occurred in
Kenya, Tanzania, Burundi, and Mongolia. All travelers planning to
visit countries in the meningitis belt during the dry season or any of
the above-mentioned countries should receive the meningitis vaccine.
The vaccination is required for pilgrims to Mecca, Saudi Arabia, for
the annual Hajj.
The formulation of meningococcal polysaccharide vaccine available in
the United States offers activity against serotypes A, C, Y, and W135.
Serotype A is responsible for most of the disease outside the United
States and Europe. Serotype C is now the most common cause of
Neisseria meningitis and is part of the vaccine. Quadrivalent
A/C/Y/W135 vaccine can be given in a single subcutaneous dose, in
the volume indicated by the manufacturer.
Primary series
1
2 & 3
1.0
0.2
Give doses 1 and 2, 13 mo apart; dose 3 is given 56 mo after
dose 2
Booster
0.2
Give booster doses 13 at 6mo intervals for persons with
ongoing exposure risks; give booster doses 4 and above at 12
year intervals after the preceding booster dose
Table
DISEASES
1.
REQUIRING
TRAVELERS'
General
Comments
SPECIAL
ATTENTION
DIARRHEA
Considerations
Ty21a
vaccine
4
48 h
5
Booster
6 y
1 Capsule1
4
48 h
Every 5 y
Vi capsular Polysaccharide
Primary series
2 y
vaccine
0.50 mL 2
1
Booster
2 y
0.50 mL 2
1
Every 2 y
Heat-phenoinactivated
Primary series
6 mo10 y
10 y
0.25 mL 3
0.50 mL 3
2
2
4 wk
4 wk
Booster
6 mo10 y
10 y
6 mo
parenteral
vaccine
0.25 mL 3
0.50 mL 3
0.10 mL 4
1
1
1
Every 3 y
Every 3 y
Every 3 y
1
, Not applicable.
Vaccination
Age
Dosage
Dose/Mode of
administration
Table
Number
of
Doses
Interval
Between
Doses
Boosting
Interval
Clinical
Findings
Diagnosis
The diagnosis of traveler's diarrhea is a clinical one. Traveler's diarrhea
is caused by a variety of bacteria, viruses, and parasites. The majority of
cases are secondary to bacterial agents. Because cultures are time
consuming and the natural course of the illness is relatively short, a
clinical diagnosis and antibiotic treatment are an appropriate approach to
treating this disease.
Treatment
Oral Rehydration. Oral rehydration is the cornerstone of therapy for
uncomplicated traveler's diarrhea. Parents should be warned that
infants and young children who are unable to communicate their
thirst and fluid needs are at risk of dehydration. Most often,
increased water intake is all that is necessary for otherwise healthy
adults. For children or persons with severe dehydration, several oral
rehydration formulations are currently marketed, or a rehydration
solution can be made with simple ingredients: a half-teaspoon of salt
can be mixed with 8 teaspoons of sugar in 1 liter of water.
Primary
series
1 & 2
0.2 mL
0.2 mL
0.3 mL
0.5 mL
Give 1 wk to 1
Booster
0.2 mL
0.2mL
0.3 mL
0.5 mL
1 dose every 6
1 Higher levels
5 years of age
mo or more apart
mo
of protection (antibody)may be achieved in children <
by the subcutaneous or intramuscular routes.
Intradermal
Route1
Doses
Table
Subcutaneous or
Intramuscular
Route
5 y of age
6
mo4
510
y of
>10
years
of
and over
y of Age
Age
Age
Comments
Antimotility
Drugs. Antimotility drugs such as loperamide
(Immodium) are safe to use for relief of symptoms in typical cases of
traveler's diarrhea. Loperamide has been shown to decrease intensity
of symptoms and shorten the course of the illness. Should the
traveler experience prolonged diarrhea, high fevers, or blood or
mucoid stools, antimotility agents should be discontinued and medical
attention sought.
Antimicrobial
415%
Rotavirus
036%
*3
Protozoa (Giardia
09%
*
spp.
Entamoeba
histolytica)
Campylobacter spp.
*
*
Vibrio
parahemolyticus
*
116%
1 Adapted from Black 1986 and Taylor & Echeverria 1986.
2 ETEC, Enterotoxigenic E coli.
3 *, Not studied.
Agent
Table
Latin
America
Asia
Prevention
Because of the large number of agents responsible for this disease,
vaccination is not an ideal form of prevention. Although investigation is
underway directed at enterotoxigenic E coli , the most common pathogen,
travelers will remain at risk of infections by the other etiologic agents.
Current forms of prevention can be directed at two routescareful
selection of food and water or chemoprophylaxis. As discussed earlier, it
is extremely important for advising physicians to educate their patient
Dose
89-17. Antimicrobial treatment of traverlers' diarrhea.
2.
TYPHOID
General
FEVER
Considerations
one of the
improved
is still some
and
Clinical
Clinical
Findings
manifestations
vary
from
asymptomatic
P.887
Diagnosis
Diagnosis is made by isolation of the bacteria in a blood culture. Stool
cultures may be negative both early and late in the illness.
Treatment
Treatment is different depending on disease manifestations. The
treatment of chronic carriers is important because they are the likely
source of disease spread. Eradication of the pathogen is difficult. Current
therapeutic options are outlined in Table 89-18 . If antibacterial therapy
is not successful, cholecystectomy may become necessary because the
bacteria tend to live in the scarred biliary tree or in the presence of
gallstones.
The treatment of choice for enteric fever is a fluoroquinolone. If
antimicrobial-agent resistance is a problem, trimethoprim-sulfa can be
used.
Prevention
Prevention of typhoid fever via vaccination (Table 89-14 ) is
recommended for travelers to developing countries who will have
prolonged exposure to contaminated food and water. As always, careful
selection of food and drink is strongly encouraged (see Pretravel
Evaluation above and Table 89-2 ).
3.
MALARIA
General
Considerations
Dose
89-18. Antimicrobial treatment of typhoid fever.
The high rate of disease and the continuing emergence of antimicrobialagent resistance are concerns with malaria treatment. Chloroquineresistant P falciparum is now reported in all countries except the
Dominican Republic, Haiti, Central America west of the Panama Canal
Zone, Egypt, and most of the Middle East (Figure 89-1 ). Pyrimethaminesulfadoxine (Fansidar) resistance has been reported in Thailand,
Myanmar, Cambodia, the Amazon area of South America, and
sporadically in sub-Saharan Africa.
Clinical
Findings
Cyclic fevers are the hallmark of plasmodium infection. The fevers occur
as the red blood cells lyse, releasing new plasmodium into the
bloodstream. Typically, the victim experiences a cold or chilling stage,
followed by a febrile stage lasting several hours, followed by a third
sweating stage. The timing of the fevers differs depending on the
infecting species48 h for P vivax and P ovale and 72 h for P malariae.
P falciparum usually causes a continuous fever with intermittent spikes.
Most victims also experience shaking chills, hypotension, cough,
headache, and back ache. Complications of the illness vary but can
include CNS involvement with delirium, seizures, coma, and renal failure.
Clinical manifestations vary somewhat depending on species.
P falciparum causes the most severe manifestations. The complications
are thought to result from diffuse microvascular disease secondary to
adherent, parasitized red blood cells that aggregate and obstruct blood
flow. Infection with P falciparum can lead to severe anemia, renal failure,
pulmonary edema, and CNS complications, referred to as cerebral
malaria, which has a range of manifestations from impaired
consciousness to seizures.
P vivax and P ovale typically cause less severe illness. The red blood cells
do not aggregate with these infections; thus the microvascular
manifestations are not seen. There is a dormant stage in the life cycle of
these plasmodia; therefore, a late secondary illness can manifest as late
as 12 months or longer after initial infection.
P malariae causes a low parasitemic infection, and associated symptoms
are typically mild. Parasitized red blood cells do not aggregate; thus,
with this infection, as well as with P vivax and P ovale , no microvascular
damage is seen later in the infection. An immune complex
glomerulonephritis is sometimes seen. The actual infection may persist
for years.
The typical laboratory findings seen with malaria are related to the
parasitized red blood cells and cell lysis. Anemia and increased lactate
dehydrogenase,
P.888
bilirubin, and reticulocyte counts are typically seen. Depending on the
extent of the disease, increased blood urea nitrogen and creatinine
associated with acute renal failure and thrombocytopenia can also be
seen.
Information
for
International
Travelers
Diagnosis
The standard diagnosis of plasmodium infection is by Giesma-stained
blood smears to visualize the parasite. The infected red blood cells can
usually be seen on a Wright's stain as well. If the clinical suspicion is
strong, and the initial blood smear is negative, the blood smear should
be repeated in 612 h.
Treatment
Successful treatment of malaria requires rapid diagnosis and initiation of
treatment. The species responsible should be confirmed via a peripheral
blood smear before initiation of treatment. The selection of the
antimalarial agent will depend on the infecting species and whether the
patient is able to take oral medications.
Patients
with P
of
of
Chloroquine-Resistant P
falciparum
Infection.
P.889
moderate malaria where the patient can take oral medication. It is
given as four tablets as a single dose daily for 3 d. It is
contraindicated in infants, pregnancy, and while breast feeding. Side
effects are rare and include nausea, vomiting, abdominal pain, and
headache. It should not be used in patients with severe renal
impairment.
P vivax, P ovale
Chloroquine phosphate, 1.0 g initially, then 500 mg at 6 h, then 500
mg daily for 2 d (Pediatric dose, 10 mg base/kg orally, then 5 mg/kg
BASEat 12, 24, and 36 h
PLUS
Primiquine phosphate, 26.3 mg daily for 14 d (Pediatric dose, 0.25
mg BASE/kg/d orally for 14 d
Side effects include nausea, anorexia, and pruritis; safe for use in
pregnancy
Contraindicated for use in G6PD-deficient patients secondary to
hemolysis risk; Contrainidicated in pregnancy
Chloroquine-sensitive
P falciparium or
P malariae
Chloroquine phosphate, 1 g orally, then 500 mg in 6 h, then 500 mg
daily for 2 d (Pediatric dosing as above)
As above
Chloroquine-resistant
P falciparum
Quinine sulfate, 600 mg (500 mg base), three times daily for 7 d
PLUS
Doxycycline 100 mg, two times dialy for 7 d
Not recommended for patients using cardiac beta blockers or those
with epilepsy or psychiatric disorders
Contraindicated in pregnancy and children under 8 y old
Malarone
Atovaquone 250 mg PLUS Proguanil
Table
Drug and
Dosages
Prevention
Prevention
against Plasmodium infection is twofold, consisting of
personal-protection measures and chemoprophylaxis. Despite complete
compliance with both medication and personal-protection measures,
infection with Plasmodium spp. is still possible. This information should
be stressed to the traveler, because a febrile illness after exposure
should be taken seriously.
Travel to areas where chloroquine resistance has not been reported
Chloroquine, 500 mg/wk. Start 2 wk before travel and continue 4 wk
after leaving malarious area [Pediatric dose 8.3 mg/kg/wk (maximum
500 mg)]
Mild; nausea, vomiting, puritis reported; safe for use in pregnancy
Travel to areas where chloroquine resistance has been reported
Mefloquine, 250 mg/wk; start 1 wk before travel and continue for 4 wk
after leaving malarious area (Pediatric doses: 1519 kg = 1/4
tablet/wk; 2030 kg = 1/2 tablet/wk; 3145 kg = 3/4 tablet/wk; >
45 kg = 1 tablet/wk)
Contraindicated in 1st trimester of pregnancy and in travelerswith history
of neuropsychiatric disorders or seizures; side effects include seizures
and psychosis reported in 1/13,000 users, nausea, dizziness, and
insomnia
OR
Doxycycline,2 100 mg/d: start 12 d before travel and continue daily
for 4 wk after leaving malarious area [Pediatric dose (after age 8 only): 1
mg/kg/d; maximum 100 mg/d]
Contraindicated in pregnancy and children < 8 y old
OR
Malarone (atovaquone 250 mg PLUS proguanil 100 mg), start one day
before travel and continue daily for 7 d after leaving the malaria area
(Pediatric dosing: 1120 kg 62.5/25, 2130 kg 125/50, 3140 kg
187.5/75, >40 kg adult dose)
Contraindicated in pregnancy, infants, nursing mothers, and renal
insufficiency Side effects nausea, vomiting, abdominal pain, and
headaches
1 Adapted from Sanford et al 2000.
2
89-20.
Malaria
Personal-protection
Side
Effects
chemoprophalactic
measures
include
the
and
Contraindications
regimens.1
general
arthropod
protection
REFERENCES
Avery ME, Snyder JD: Oral therapy for acute diarrhea. The underused
simple solution. N Engl J Med 1990; 323:891.
Black RE: Pathogens that cause travelers' diarrhea in Latin America
and Africa. Rev Infect Dis 1986;8(Suppl 2): S131.
Information
for
1981;84:239.
Health
2001
McGraw-Hill
90
Zoonotic
Infections
Scott D. Smith MD
David A. Relman MD
Essentials
of
Diagnosis
General
Considerations
zoonoses are farmers, hunters, and those that handle and work with ani
vectors and those that work in and near water are at increased risk for
disease agents; ie, they do not contribute to overall, long-term persistenc
most common reservoirs for human zoonotic diseases are domestic anima
their homes and move into the habitats of the primary reservoirs, their
lists some of the more common associations of animals with zoonotic ag
P.893
Biological vectors on the other hand may have a sophisticated and acc
and cyclic development within vector gut or salivary glands. It is commo
respond to the relevant cues by expressing a unique set of genes and
For example, B burgdorferi preferentially expresses the surface protein Os
its translocation through the tick gut wall. Nocturnal biting patterns of t
human filariasis, match the nocturnal periodicity of parasitemia of the m
enhance transmission efficiency or competence; for example, the Simuliu
dwelling microfilaria of Onchocerca
volvulus.
P.895
multocida from animal bites) or by direct inoculation (eg, cutaneous ant
or Chlamydia psittaci ), and (3) by ingestion (eg, Giardia lamblia or Bruc
nature of the ensuing clinical syndrome in the human host, especially wi
transmitted to humans by more than one route; for example, C burnetii
can be acquired from a tick as well as through
P.896
direct inoculation of the skin from an abrasion while handling an infected
from the route between reservoir hosts.
Virus
Rabies
Rabies
Rabies
Hanta
virus
Rabies
virus
Influenza
Lymphocytic
Viral
Viral
choriomeningitis
encephalitis
encephalitis
Bacterium
Pasteurella
multocida
Pasteurella
multocida
Campylobacter
jejuni
Pasteurella
multocida
Pasteurella
multocida
Salmonella spp.
Salmonella spp.
Salmonella spp.
Salmonella spp.
Salmonella spp.
Bacillus anthracis
Bacillus anthracis
Bacillus anthracis
Bacillus anthracis
Brucella
canis
virus
Campylobacter
jejuni
Salmonella spp.
Francisella
tularensis
Salmonella spp.
Yersinia
enterocolitica
Yersinia
enterocolitica
Streptococcus
iniae
Campylobacter
jejuni
Yersinia
enterocolitica
Brucella spp.
Brucella spp.
Brucella spp.
Brucella spp.
Campylobacter
jejuni
Capnocytophaga
canimorsus
Listeria
monocytogenes
Yersinia pestis and Y enterocolitica
Yersinia pestis and Y enterocolitica
Campylobacter
jejuni
Campylobacter
jejuni
Mycobacterium
marinum
Listeria
monocytogenes
Edwardsiella tarda
Babesia spp.
Leptospira spp.
Leptospira spp.
Borrelia
burgdorferi
Yersinia pestis
Leptospira spp.
Streptobacillus
moniliformis or Spirillium
Pasteurella spp.
Aeromonas spp.
Erysepelotrix
rhusiopathiae
Pasteurella spp.
Plesiomonas spp.
minus
Campylobacter spp.
Campylobacter spp.
Borrelia spp.
Leptospira
interrogans
Coxiella burnetti
Leptospira spp.
Leptospira spp.
Vibrio cholerae
Chlamydia psittaci
Leptospira spp.
Erysipelothrix
rhusiopathiae
Francisella
Francisella
Salmonella
Salmonella
tularensis
tularensis
spp.
spp.
Yersinia
enterocolitica
Listeria
monocytogenes
Listeria
monocytogenes
Salmonella spp.
Listeria
monocytogenes
Francisella
tularensis
Francisella
tularensis
Borrelia spp.
Leptospira spp.
Campylobacter
jejuni
Yersinia
enterocolitica
Coxiella burnettii
Coxiella burnettii
Rickettsia
rickettsiae
Francisella
tularensis
Francisella
tularensis
Salmonella spp.
Salmonella spp.
Salmonella spp.
Pasteurella
multocida
Yersinia
enterocolitica
Yersinia
Yersinia
enterocolitica
enterocolitica
Rickettsia
rickettsiae
Parasite
Giardia lamblia
Giardia lamblia
Giardia lamblia
Cheyletiella parasitovorax
Babesia microti
Hymenolepis nana
Diphyllobothrium
latum
Cryptosporidium
Cryptosporidium
Cryptosporidium
Cryptosporidium
(rabbit
fur
mite)
spp.
spp.
spp.
spp.
Cryptosporidium spp.
Toxocara canis
Toxocara cati
Toxocara spp.
Toxoplasma
gondii
Toxoplasma gondii
Cryptosporidium
parvum
Cryptosporidium
parvum
Taenia saginata
Giardia lamblia
Ancylostoma spp.
Toxoplasma gondii
Fungus
Dermatophytes
Dermatophytosis
Dermatophytosis
(Trycophyton
mentagrophytes )
(T. mentagrophytes )
Cryptococcus
neoformans
Taenia solium
Taenia solium
Histoplasma
1
capsulatum
These lists are not all-inclusive, but rather are meant to highlight dise
Animal
Table
Dog
Cat
Ferret
Rabbit
Rats
and
Mice
Hamster
and
Guinea
Pig
Turtle
Fish
More
Frequent 1
Listeria
monocytogenes
Toxoplasma gondii (in immunocompromised hosts)
Coxiella burnetii
Histoplasma
capsulatum
Giardia lamblia
Cryptosporidium
parvum
Salmonella spp.
Campylobacter
jejuni
Rickettsia rickettsii, R. typhi, R. conorii
Dengue fever virus
Salmonella
typhi
Borrelia
burgdorferi
Pasteurella
multocida
Trypanosoma cruzi
Toxoplasma gondii
Bartonella
henselae
Less
Frequent 1
gambiense
or
rhodiense
Bacillus anthracis
Chlamydia psittaci
Francisella
tularensis
Toxocara canis
Yersinia pestis
Sin Nombre hantavirus
Echinococcus
granulosus
Brucella spp.
Trichinella
spiralis
Anisakis spp.
Echinococcus
granulosus
Taenia solium (pig) or saginata (cow)
Listeria
monocytogenes
Yersinia
enterocolitica and Y.
pseudotuberculosis
Campylobacter
jejuni
Isospora belli
Babesia microti and related spp.
Ehrlichia spp.
Brucella abortus
Pseudomonas mallei
Spirillum minor
Borrelia
recurrentis
Trichinella
spiralis
Histoplasma
capsulatum
Acute infection:
African Trypanosoma
Francisella
tularensis
Bacillus
anthracis
Cowpox virus
Orf virus
Erysipelothrix
rhusiopathiae
Rickettsia conorii
Orientia
tsutsugamushi
Mycobacterium
marinum
Spirillum minor
Streptobacillus
moniliformis
Seal finger agent
Yersinia pestis
Francisella
tularensis
Dengue virus
Brucella spp.
Histoplasma
capsulatum
Leishmania spp.
Acute Trypanosoma infection: African and American
Francisella
Trichinella
1
tularensis
spiralis
Nervous
System
Pulmonary
Clinical
Findings
associated with zoonotic disease reflect the route of transmission. For examp
local cutaneous disease such as ulcers, cellulitis, or regional lymphadenopath
syndromes; and agents that are transmitted by ingestion usually lead to ab
limited to the subset of zoonotic agents that use that route of transmission.
cutaneous eschar (eg, Mediterranean and other spotted fevers and scrub ty
anthrax); and fever, preauricular lymphadenopathy, and conjunctivitis or Pa
Figure 90-2. The overlap and interplay between emerging infectious disease
permission, from Daszak P et al: Emerging infectious diseases of wildlife. S
Diagnosis
Treatment
The diversity of zoonotic agents precludes any simple protocol for empiric th
to empiric therapy because of a restricted
P.897
P.898
list of possible zoonotic pathogens that share susceptibility to a few common
States in a person with a recent tick bite can be treated empirically with d
reasonably good treatment for the following tick-borne diseases: Lyme disea
fever. Some zoonoses such as Rocky Mountain spotted fever and anthrax ar
therapy.
Fever Rash and Animal/Vector Exposure3
First Choice
Chloramphenicol,
50100
mg/kg/d
Choice
Lymphadenopathy,
and
Animal/Vector
Exposure5
Choice
Choice
Choice
Allergic
and
Animal/Vector
Exposure7
Choice
and
Animal/Vector
Exposure8
Choice
Trimethoprim-sulfamethoxazole,
Trimethoprim-sulfamethoxazole,
1
612
160
mg/kg/d
mg/800
mg
twice
daily
The route of administration for any of these antibiotics depends on the sev
specific drug (eg, streptomycin, intramuscularly).
3 Must make diagnosis immediately if malaria is suspected.
4
Adults
Prophylactic
Measures
parturient
animals
Precautions
Fever,
and
Lymphadenopathy,
Animal/Vector
Exposure
Fever, Local
Lesion, and A
Expos
Control
The complexity that governs the origin and spread of zoonoses also provides
intervention and interruption (Box 90-3 ). Lyme disease is a useful example
detection and removal of attached ticks, tick reduction, by making acaricidevaccination of humans. OspA is a potent immunogen and is the basis of the
be expanded in some cases to other hosts: the spread of rabies in the easte
vaccine-laden bait) and peridomestic animals that have close contact with p
REFERENCES
Chomel BB: Zoonoses of house pets other than dogs, cats and birds. Ped
Talan DA et al: Bacteriologic analysis of infected dog and cat bites. N Engl
Tan JS. Human zoonotic infections transmitted by dogs and cats. Arch Inte
Walker DH et al: Emerging bacterial zoonotic and vector-borne diseases. J
2001
McGraw-Hill
91
Ectoparasitic Infestations
Arthropod Stings & Bites
&
Walter R. Wilson MD
James M. Steckelberg MD
Ectoparasitic infestation is extremely common worldwide and
virtually every human who resides in nonpolar climates is bitten
repeatedly by arthropods. Specific infectious diseases
transmitted by arthropod bite are reviewed elsewhere in this
book. This chapter describes ectoparasitic infestations and toxic
reactions to arthropod stings and bites. There is considerable
overlap between infestations and bites because ectoparasites
either bite or burrow under the skin of their human host.
ECTOPARASITIC
Essentials
of
INFESTATION
Diagnosis
or clothing
Fleas: history of exposure or capture of organism
Myiasis: demonstration of maggots in tissue
Leeches: history of exposure, capture of organism
General
Considerations
Table
Species
Ticks
Ixodes spp.
Dermacentor spp.
Site
Infested
Amblyomma
americanum
Mites (Sarcoptes
scabiei)
Lice
P humanus var.
capititis
P humanus var.
corporis
Pthirus pubis
axillary
Fleas
Ctenocephalides
spp.
Xenopsylla
cheopis
Leeches
H medicinalis
Haemadipsa spp.
Medicinal leech
Aquatic and land leeches
attach to exposed human skin
Myiasis (maggots)
Dermatobia
hominis
Gasterophilus
intestinalis
hair,
eyelashes
Phoenicia spp.
pustulates,
and
ulcerates.
carpets,
on shed
rhinitis,
in sensitized
creatures.
Ectoparasite
(infestation)
Ticks
Mites
(scabies)
Lice
More
Common
Less
Common
Pruritic
papulonodule,
Fever,
malaise,
erythema
Eschar
myalgias,
paralysis
Erythematous,
pruritic
Crusted thick
keratotic
maculopapular
rash
Pruritic
erythematous
burrows
lesions,
scaling,
dystrophic
nails
Head: crusted,
pruritic oozing
lesions, matted
hair
Blepharitis
Body: pruritic,
erythematous
maculopapular
rash
Pubic: pruritic
maculopapular
bluish lesions
Fleas
Pruritic,
erythematous
papules,
urticaria
Flies
(myiasis)
Maggots in
furuncles,
Vesicles,
anaphylaxis
wounds, or
body cavities
Creeping
dermal myiasis
Secondary
bacterial
infection
Leeches
Shallow
bleeding
ulcers
Sepsis
secondary
bacterial
infection from
Aeromonas
hydrophila
Differential
Diagnosis
Treatment
The treatment for ectoparasitic infestation is shown in Box 91-2.
Secondary bacterial infections should be treated with appropriate
antimicrobial therapy. Tetanus toxoid should be administered as
needed in patients with significant cutaneous wounds, such as
those caused by myiasis, leeches, or other infestation.
Prognosis
Prevention
Prevention of tick infestation is facilitated by avoiding brushy
vegetation, wearing protective clothing, tucking the trouser cuffs
inside socks, and spraying clothing with 0.5 permethrin or an
application of repellents containing N, N-diethyl-m-toluamide
(DEET). Health care workers who treat patients with crusted
scabies should wear protective gowns and gloves. Close contacts
with patients with scabies should be treated even if they are
asymptomatic. Bedding and clothing should be washed with hot
soapy water. Combs and brushes belonging to patients infested
with lice should be disinfected in hot water (65C) for 515
min or soaked in insecticide for at least one hour. Clothing and
bedding may be deloused by washing in hot water and drying in
a clothing dryer at 65C for 3045 min or by fumigation with
insecticide. Thorough cleaning of carpets, furniture, curtains,
and other fabrics may reduce house mites. Fleas may be killed
by spraying or dusting their nesting sites with insecticide.
Myiasis risk may be reduced by good hygiene, including washing
with soap and water after horseback riding or fly exposure.
Openly draining wounds should be cleaned and dressed
regularly. Wearing protective clothing reduces the risk of
infestation by land or aquatic leeches.
Ectoparasite
(infestation) and
patient group
Ticks
(tick
paralysis)
First
Choice
Alternative 1
remove
tick
Scabies (mites)
Immunocompetent
5% Permethrin
cream from chin
Ivermectin,
200 g/kg,
patients
Immunosuppressed
patients (AIDS)
to toes; remove
8 h later with
soap and water;
repeat in 1
single
dose
oral
Lice
1% Permethrin
to hair, body, or
pubic areas kills
lice and eggs;
comb hair with
nit comb after
rinsing hair.
See text for
clothing
treatment
Fleas
Myiasis
Leeches
0.5%
Malathion is
less
effective. 1%
Lindane is
less effective
and more
toxic
P.903
ARTHROPOD
Essentials
STINGS
of
&
BITES
Diagnosis
vesiculopustule,
history
of
exposure
General
Considerations
Table
Species
Apis
mellifera
Common
Name
Honey bee
Apis spp.
Wasps, hornets,
jackets
Bombus spp.
Bumble bee
Solenopsis spp.
Ants
Loxosceles
reclusa
yellow
Latrodectus
mactans
Centruroides spp.
Scorpions
Arthropod
More
Common
Hymenoptera
Immediate
(bee, wasp,
hornet,
yellow
pain,
flair
jacket,
Less
Common
Anaphylaxis
wheel,
ant)
Ant
Immediate
pain,
erythema,
edema,
vesicle,
pustule
Spider
Brown
recluse
(Loxosceleus
reclsa)
Minimal
initial pain
Later pain,
pruritic
Extensive
necrosis
Myalgias,
nausea,
lesion central
induration
surrounded
vomiting,
hemolytic,
anemia, death
by zones of
ischemia,
erythema
Hemorrhagic
neurosis,
eschar
necrosis
Black
widow
Minimal
initial pain,
Extreme
rigidity,
(Latrodectus
mactans)
two
erythematous
fang bites,
painful
rhabdomyolysis,
respiratory
arrest, death
muscle
cramps
Scorpion
Most
Immediate
scorpions
pain, wheal
flair
erythema,
edema
C
sculpturatus
Pain,
paresthesia,
muscle
cramps,
twitching,
profuse
salivation
Anaphylaxis
Cranial nerve or
muscle
paralysis,
rhabdomyolysis,
respiratory
arrest, death
Differential
Diagnosis
sculpturatus
Treatment
Treatment of arthropod stings and bites is outlined in Box 91-4.
Administration of antihistamines, topical corticosteroids, and
antimicrobial agents for secondary bacterial infection are general
therapeutic measures for symptomatic arthropod stings.
Anaphylaxis is treated by the administration of subcutaneous or,
in severe cases, intravenous epinephrine, fluid resuscitation,
bronchodilators, and, if necessary, endotracheal intubation and
vasopressors. Patients with a history of severe allergy or
anaphylaxis associated with insect stings should carry
commercially available kits to treat anaphylaxis and other
serious reactions when engaging in activities that place them at
risk of arthropod exposure. Desensitization injections reduce the
risk of recurrent anaphylaxis in hypersensitized individuals for
bee and hornet stings.
Arthropod
Hymenoptera
Treatment
See text for symptomatic therapy
Spiders
Brown recluse
(Loxosceles
reclusa)
Black widow
(Latrodectus
mactans)
Scorpions
Most species
Centruroides
sculpturatus
Prognosis
The prognosis for most individuals after arthropod stings is
excellent. Most deaths result from anaphylaxis. Deaths are rare
in treated patients envenomated by brown recluse spiders, black
widow spiders, or C sculpturatus scorpions.
Prevention
Spraying insecticides in dark areas inhabited by spiders reduces
the risk of exposure. When camping outdoors, individuals should
check their shoes, backpacks, and sleeping bags for scorpions.
REFERENCES
Goddard