SEPSIS NEONATORUM

Source: Nelson Textbook of

Pediatrics
20th Edition
Chapter 109; Pages 909-925;
Copyright 2016

ALCANTARA, EDUARD L.
Group 6 Subgroup A
August 12, 2016 (Friday)

Objectives:
O At the end of the presentation, will be able to:
O Define Sepsis Neonatorum.
O Describe the pathogenesis of the involved disease

entities.
O Interpret the signs and symptoms basing from the

given guidelines.
O Compare each disease entity.
O Integrate respect, integrity, compassion and esteem

to patient care.

O Figure 1-10 Global causes of child deaths

. CHERG, Child Health Epidemiology Reference Group; GBD,
Global

Burden of Disease study.

1 Neonatal Infections
1. Infectious agents mother fetus/newborn
infant (diverse modes).
2. The fetus and newborn infant (less capable
of responding to infection) immunologic
immaturity.
3. Coexisting conditions often complicate the
diagnosis and management of neonatal
infections.
4. The clinical manifestations of newborn
infections vary.

Neonatal Infections
5. Maternal infection (source of transplacental
fetal infection) is often undiagnosed during
pregnancy.
6. A wide variety of etiologic agents infect the
newborn bacteria, viruses, fungi, protozoa,
and mycoplasmas.
Very-low birthweight (VLBW) newborns, they
remain in the hospital for a long time in an
environment that puts them at continuous risk
for acquired infections.

2 Modes of Transmission and

Pathogenesis
O Intrauterine infection: a result of clinical or subclinical maternal infection

with a variety of agents and hematogenous transplacental transmission to

the fetus. Transplacental infection may occur at any time during gestation,
and signs and symptoms may be present at birth or may be delayed for
months or years (Fig. 109-1). Infection may result in early spontaneous
abortion,

congenital

malformation,

intrauterine

growth

restriction,

premature birth, stillbirth, acute or delayed disease in the neonatal

period, or asymptomatic persistent infection with sequelae later in life. In
some cases, no apparent effects are seen in the newborn infant.

Modes of Transmission and

Pathogenesis
O The timing of infection during gestation affects the

outcome.

First

trimester

infection

may

alter

embryogenesis, with resulting congenital malformations

(congenital rubella) (see Chapter 247). Third-trimester
infection often results in active infection at the time of
delivery (toxoplasmosis, syphilis). Infections that occur
late in gestation may lead to a delay in clinical
manifestations until after birth (syphilis).

Modes of Transmission and

Pathogenesis
O Maternal infection is a necessary prerequisite for transplacental

infection.

For

some

etiologic

agents

(rubella),

maternal

immunity is effective and antibody is protective for the fetus.

For other agents (CMV), maternal antibody may ameliorate the
outcome of infection or may have no effect (see Chapter 255).
Even without maternal antibody, transplacental transmission of
infection to a fetus is variable because the placenta may
function as an effective barrier.

PATHOGENESIS OF ASCENDING
BACTERIAL INFECTION
O In most cases, the fetus or neonate is not exposed to potentially

pathogenic bacteria until the membranes rupture and the infant

passes through the birth canal and/or enters the extrauterine
environment.

PATHOGENESIS OF LATE-ONSET
POSTNATAL INFECTIONS
O After birth, neonates are exposed to infectious agents:

nursery or in the community (including family).

O Postnatal infection: direct contact with hospital personnel,

the mother, or other family members; from breast milk

(HIV,

CMV);

or

from

inanimate

sources

such

as

contaminated equipment.
O The

most common source of postnatal infections in

hospitalized newborns is hand contamination of healthcare

personnel, underscoring the importance of handwashing.

3 Immunity
O 1st 3 mo life, the innate immune system

phagocytes, natural killer cells, antigen

presenting cells, and complement provide
defense against pathogens.
O With advancing age and exposures, the
acquired immune system develops and
assumes a more prominent role in host
defense.
O

function of neutrophils and low concentrations of

immunoglobulins increases the susceptibility of preterm
infants to invasive infection.

Immunity
A. IMMUNOGLOBULIN: IgG, actively transported across
the placenta, with concentrations in a full-term infant
comparable to or higher than maternal levels, because of
a combination of both acquired and neonatally produced
IgG in the third trimester.
O In

premature infants, cord IgG levels are directly

proportional to gestational age; @18-20 wk, IgG levels

are <100 mg/dL and reach 400 mg/dL by 30-32 wk of
gestation.

Immunity
O Physiologic hypogammaglobulinemia: Levels of maternally

derived IgG fall rapidly after birth in a process with notable

implications for premature and small-for-gestational-age
neonates, whose IgG levels are often reduced compared
with term and appropriate-for-gestational- age neonates.
O Other classes of immunoglobulins (IgA, IgM, IgD, and IgE)

are not transferred across the placenta, therefore elevated

cord blood levels of IgA and IgM may be evidence of an
intrauterine infection.

Immunity
O Term and premature infants are able to mount immune responses

to protein antigens including tetanus, diphtheria, hepatitis, and

polio but are impaired in their ability to respond to polysaccharide
antigens such as Haemophilus influenzae type b and group B
streptococci.
O Conjugate vaccines join polysaccharide antigens to immunogenic

proteins giving the appearance of a T-cell dependent antigen to

the immature neonatal immune system.

Immunity
B. COMPLEMENT - A fetus begins to synthesize complement
components: weeks 6-14; transplacental passage of complement
from the maternal circulation does not occur.
O It mediates bactericidal activity against certain organisms

such as E. coli and functions as an opsonin with antibody in

the phagocytosis of GBS.
O Fullterm newborn infants have slightly diminished classical

pathway complement activity and moderately diminished

alternative pathway activity.
O Premature infants: lower levels of complement components

and less complement activity, and have notably reduced

Immunity
C. NEUTROPHIL FUNCTION
O

Term and late preterm: have impaired neutrophil function compared with that of
older infants.

Quantitative and qualitative deficiencies of the phagocyte system contribute to

the newborns susceptibility to infection.

Neutrophil migration (chemotaxis), adhesion, aggregation, and deformability, all of

which may be impaired in the neonate, may delay the response to infection.
Abnormal expression of cell membrane adhesion molecules (the 2 integrins and
selectins) and abnormalities in the neonatal neutrophil cytoskeleton contribute to
impaired chemotaxis.

Immunity
O Impairment

of

the

oxidative

respiratory

burst

of

neonatal neutrophils is a factor in the increased risk of

sepsis (especially preterm infants).
O Neutrophil

granules

contain

enzymes;

one

noted

protein is bactericidal/permeability-increasing protein

(BPI) that binds to the endotoxin in the cell wall of
Gram-negative bacteria. BPI facilitates opsonization
and prevents the inflammatory response to endotoxin.
BPI activity may be decreased in neonates.

Immunity
NEUTROPHIL NUMBER
O Neutropenia: appears to be a better predictor of neonatal sepsis than

leukocytosis, although neutropenic ranges differ by gestational age,

mode of delivery, altitude of location of birth, and sampling methods.
O Neonates have a 70-80% reduction in bone marrow neutrophil stores

compared to adults and therefore are impaired in their response to

infectious and noninfectious stressors. Increasing neutrophil number
with granulocyte colony-stimulating factors (G-CSFs) o
granulocytemacrophage colony-stimulating factors (GM-CSFs),
cytokines that stimulate myeloid progenitor cells, does not appear to
affect clinical outcomes.

Immunity
O Natural Killer Cells: are a subgroup of lymphocytes that

are cytolytic against cells infected with viruses. NK cells

also lyse cells coated with antibody in a process called
antibody-dependent cell-mediated cytotoxicity.
O NK cells appear early in gestation and are present in

cord blood in numbers equivalent to those in adults;

neonatal NK cells have an approx. 50% decrease in
cytotoxic activity and antibody dependent cell-mediated
cytotoxicity in comparison with NK cells from adults.

Immunity
CYTOKINES/INFLAMMATORY MEDIATORS
O Several

adverse

outcomes

brain

injury,

necrotizing

enterocolitis, and bronchopulmonary dysplasia (BPD), may be

mediated by an unbalanced cytokine (proinflammatory vs.
antiinflammatory) response to infection.
O The release of tumor necrosis factor-, interleukin (IL)-1 (IL-

1), IL-4, IL-6, IL-8, IL-10, IL-12, platelet-activating factor, and

the leukotrienes offers the potential opportunity to facilitate
an early laboratory diagnosis of infection.

4 Etiology of Fetal and

Neonatal Infection
O

number

of

bacterial

and

nonbacterial (Table 109-1) agents

may

infect

newborns

intrapartum,
Intrauterine

or

in

utero,

postpartum.
transplacental

infections of significance to the

fetus

and/or

syphilis,

newborn
rubella,

include
CMV,

toxoplasmosis, parvovirus B19, and

varicella.

Etiology of Fetal and

Neonatal Infection
O Although HSV, HIV, hepatitis B virus, hepatitis C

virus, and tuberculosis (TB) can each result in

transplacental infection, the most common mode
of transmission for these agents: intrapartum,
during labor and delivery with passage through an
infected birth canal (HIV, HSV, hepatitis B virus),
or postpartum, from contact with an infected
mother or caretaker (TB) or with infected breast
milk (HIV).

Etiology of Fetal and

Neonatal Infection
O Any microorganism inhabiting the

genitourinary or lower gastrointestinal tract

may cause intrapartum and postpartum
infection the m.c. bacteria are GBS and E. coli.
O The more common viruses are CMV, HSV,
enteroviruses, and HIV.

Etiology of Fetal and

Neonatal Infection
O Common agents in

Healthcare-associated
infections (HAIs) in the newborn: coagulasenegative staphylococci, Gram-negative bacilli
(E. coli, Klebsiella pneumoniae, Enterobacter,
Pseudomonas
aeruginosa),
enterococci,
Staphylococcus aureus, and Candida. Viruses
contributing to HAIs in the neonate include
enteroviruses, CMV, hepatitis A, adenoviruses,
influenza, RSV, rhinovirus, parainfluenza, HSV,
and rotavirus.

Etiology of Fetal and

Neonatal Infection
O Community-acquired pathogens such as Streptococcus pneumoniae may

also cause infection in newborn infants after discharge from the hospital.
O Congenital pneumonia may be caused by CMV, rubella virus, and T.

pallidum

and,

less

commonly,

by

the

other

agents

producing

transplacental infection (Table 109-2).

O Microorganisms causing pneumonia acquired during labor and delivery

include GBS, Gram-negative enteric aerobes, Listeria monocytogenes,

genital Mycoplasma, Chlamydia trachomatis, CMV, HSV, and Candida
species.

Etiology of Fetal and

Neonatal Infection

Etiology of Fetal and

Neonatal Infection
O

Bacteria responsible for most cases of nosocomial pneumonia typically include

staphylococcal species, Gram-negative enteric aerobes, and occasionally,
Pseudomonas.

Fungi are responsible for an increasing number of systemic infections, usually

acquired during prolonged hospitalization of preterm neonates. Respiratory
viruses cause isolated cases and outbreaks of nosocomial pneumonia. These
viruses, usually endemic during the winter months and acquired from infected
hospital staff or visitors to the nursery, include RSV, parainfluenza virus,
influenza viruses, and adenovirus.

Etiology of Fetal and

Neonatal Infection
O Respiratory viruses: single most important cause of community-acquired

pneumonia and are usually contracted from infected household contacts.

O The m.c. bacterial causes of neonatal meningitis are GBS, E. coli, and L.

monocytogenes. S. pneumoniae, other streptococci, nontypable H.

influenzae,

both

coagulase-positive

and

coagulase-negative

staphylococci, Klebsiella, Enterobacter, Pseudomonas, T. pallidum, and

O Mycobacterium

tuberculosis infection involving the central nervous

system may also result in meningitis.

Epidemiology of Early- and

Late-Onset Neonatal Infections
O Early onset infections are acquired before or during delivery (vertical

mother-to-child transmission).
O Late-onset infections develop after delivery from organisms acquired

in the hospital or the community.

O The age at onset depends on the timing of exposure and virulence of

the infecting organism.

O Very-late-onset infections (onset after 1 mo of life) may also occur,

particularly in VLBW preterm infants or term infants requiring

prolonged neonatal intensive care.

Epidemiology of Early- and

Late-Onset Neonatal Infections
O The incidence of neonatal bacterial sepsis varies from 1-4/1,000 live births, with

geographic variation and changes over time.

O Studies suggest that term male infants (vs term females) have a higher incidence

of sepsis. This sex difference is less clear in preterm low birthweight (LBW)
infants.
O Attack rates of neonatal sepsis increase significantly in LBW infants in the

presence of maternal chorioamnionitis, congenital immune defects, mutations of

genes involved in the innate immune system, asplenia, galactosemia (E. coli),
and malformations leading to high inocula of bacteria (obstructive uropathy).

Epidemiology of Early- and

Late-Onset Neonatal Infections

Epidemiology of Early- and

Late-Onset Neonatal Infections
O Intrapartum antibiotics : are used to reduce vertical

transmission of GBS as well as to lessen neonatal

morbidity after preterm rupture of membranes.
O With introduction of selective intrapartum antibiotic

prophylaxis to prevent perinatal transmission of GBS,

rates of early-onset neonatal GBS infection in the
United States declined from 1.7/1,000 live births to
0.25/1,000, according to U.S. Centers for Disease
Control and Prevention (CDC) surveillance data.

Epidemiology of Early- and

Late-Onset Neonatal Infections
O Intrapartum chemoprophylaxis does not reduce

the rates of late-onset GBS disease and has no

effect on the rates of infection with non-GBS
pathogens. Of concern is a possible increase in
gram-negative infections (especially E. coli) in
VLBW and possibly term infants in spite of a
reduction in early GBS sepsis by intrapartum
antibiotics.

Epidemiology of Early- and

Late-Onset Neonatal Infections
O The

incidence of meningitis is 0.20.4/1,000 live births in newborn infants

and is higher in preterm infants.
O Bacterial meningitis may be associated
with sepsis or may occur as a local
meningeal infection.
O Up to one-third of VLBW infants with
late-onset meningitis have negative
blood culture results.

Epidemiology of Early- and

Late-Onset Neonatal Infections
OThe discordance between results of

blood and cerebrospinal fluid (CSF)

cultures suggests that meningitis may
be underdiagnosed among VLBW
infants and emphasizes the need for
culture of CSF in VLBW infants when
late-onset sepsis is suspected and in
all infants who have positive blood
culture results.

PREMATURITY
O The

most
important
neonatal
factor
predisposing to infection is prematurity or LBW.
Preterm LBW infants have a 3- to 10-fold higher
incidence of infection than full-term normal
birthweight infants.

109.6 HealthcareAssociated Infections (HAI)

O HAIs are responsible for significant morbidity
and late mortality in hospitalized newborns,
with almost 25% of VLBW infants (<1,500 g
birthweight)
experiencing
1
or
more
nosocomial infections.
O Majority HAIs: occur in preterm or term infants
who require intensive care.

109.6 HealthcareAssociated Infections (HAI)

Risk factors for HAIs in these infants: prematurity, low
birthweight,
catheters,

invasive
parenteral

procedures,
nutrition

indwelling

with

lipid

vascular
emulsions,

endotracheal tubes, ventricular shunts, alterations in the skin

and/or mucous membrane barriers, frequent use of broadspectrum antibiotics, and prolonged hospitalization.
O The

most

frequent

HAIs:

bloodstream

infections

a/w

intravascular catheters and ventilator-associated pneumonia.

O HAIs may also occur in the absence of a

catheter or ventilator.
O Infants receiving intensive care are at risk for
community or HAIs during seasonal epidemics
(RSV, influenza).
O Neonatal immunization during the birth
hospitalization most reliable point of
healthcare contact.

O The mean age at onset of the first episode of

late-onset HAI sepsis occurs during 2-3 wk of

life, independent of the infecting pathogen.
O HAIs increase the risk of adverse outcomes,
including prolonged hospitalization and
mortality.

O The

emergence of bacterial pathogens

resistant to multiple antibiotics is a growing
concern.
O The emergence of methicillin-resistant S.
aureus, vancomycin-resistant enterococci, and
multidrug-resistant Gram-negative pathogens
are
particularly
alarming.
Organisms
responsible for neonatal bacterial sepsis and
meningitis as well as HAIs fluctuate with
antimicrobial pressure.

O Viral pathogens including RSV, varicella,

influenza, rotavirus, and enteroviruses may be

responsible for sporadic infections or for out
breaks in the NICU.
O Infection prevention policies, including
immunization of healthcare providers, visitors,
and neonates, when feasible, are essential to
prevent and/or contain nursery infection
outbreaks.

O Prevention

of transmission: standard precautions with all patient

contact, maintaining a manageable unit census with appropriate nurse:

patient ratios, strict compliance with hand hygiene, meticulous neonatal
skin care, minimizing the risk of catheter contamination, decreasing the
number of venipunctures and heelsticks, reducing the duration of
catheter and mechanical ventilation days, encouraging appropriate
advancement of enteral feedings, providing education and feedback to
nursery personnel, and ongoing monitoring and surveillance of HAIs in
the NICU.

O Hand hygiene: the most important and effective means of

reducing HAIs.
O Proper hand hygiene with either soap and water or alcohol-

based hand sanitizers is essential before and after each

patient contact.
O The use of gloves
O Skin to skin contact has proven beneficial to the neonate.
O Ongoing education of staff regarding practices that are likely

to reduce HAIs and promote active surveillance are important

components of infection prevention.

Clinical Manifestations of
Transplacental Intrauterine
Infections

BACTERIAL SEPSIS

SYSTEMIC INFLAMMATORY
RESPONSE SYNDROME
O The clinical manifestations of infection depend

on the virulence of the infecting organism and

the bodys inflammatory response.
O Systemic inflammatory response syndrome
(SIRS) is most frequently used to describe this
unique
process
of
infection
and
the
subsequent systemic response (see Chapters
70 and 177). In addition to infection, SIRS may
result from trauma, hemorrhagic shock, other
causes of ischemia, necrotizing enterocolitis,
and pancreatitis.

O Patients with SIRS have a spectrum of clinical

symptoms that represent progressive stages of

the pathologic process.
O In adults, SIRS is defined by the presence of 2
or more of the following: (1) fever or
hypothermia, (2) tachycardia, (3) tachypnea,
and (4) abnormal white blood cell (WBC) count
or an increase in immature forms.

O In

neonates

manifests

and
as

pediatric

patients,

temperature

SIRS

instability,

respiratory dysfunction (altered gas exchange,

hypoxemia,

acute

respiratory

distress

syndrome), cardiac dysfunction (tachycardia,

delayed

capillary

refill,

hypotension),

and

perfusion abnormalities (oliguria, metabolic

acidosis).

O Increased vascular permeability results in

capillary leak into peripheral tissues and

the lungs, with resultant peripheral and
pulmonary edema. DIC results in the more
severely affected cases. The cascade of
escalating

tissue

injury

may

lead

multisystem organ failure and death.

to

Fever
O Fever - Only approximately 50% of infected newborn infants have a

temperature higher than 37.8C (100F) (axillary) (see Chapters 176, 177).
O Fever (newborn infants) does not always signify infection; it may be caused

by increased ambient temperature, isolette or radiant warmer malfunction,

dehydration, central nervous system (CNS) disorders, hyperthyroidism,
familial dysautonomia, or ectodermal dysplasia.
O A single temperature elevation is infrequently associated with infection;

fever sustained over 1 hr is more likely to be caused by infection.

Rash
O Rash: Cutaneous manifestations of infection

include omphalitis, cellulitis, mastitis, and

subcutaneous abscesses.
O Ecthyma gangrenosum is indicative of
infection with Pseudomonas species. The
presence of small salmon-pink papules suggests
L. monocytogenes infection.
O A vesicular rash is consistent with herpesvirus
infection.
O The mucocutaneous lesions of Candida albicans
are discussed elsewhere (see Chapter 234.1).

Rash
O Petechiae and purpura may have an infectious

cause. Purple papulonodular lesions are

referred to as blueberry muffin rash and
represent dermal erythropoiesis. Causes
include congenital viral infections CMV,
rubella, and parvovirus), congenital neoplastic
disease, and Rh hemolytic disease.

Omphalitis
O Omphalitis: a neonatal infection resulting from unhygienic

care of the umbilical cord, which continues to be a problem,

particularly in developing countries.
O The

umbilical stump is colonized by bacteria from the

maternal genital tract and the environment (see Chapter 105).

O The necrotic tissue of the umbilical cord is an excellent

medium for bacterial growth.

Tetanus
O D/t unclean delivery and unhygienic management of the

umbilical cord in an infant born to a mother who has not been

immunized against tetanus.
O Surveillance case definition: requires the ability of a newborn

to suck at birth and for the 1st few days of life, followed by an
inability to suck starting between 3 and 10 days of age,
difficulty swallowing, spasms, stiffness, seizures, and death.
O Bronchopneumonia

cause of death.

(aspiration),

is

common

complication;

Pneumonia
O Early signs and symptoms of pneumonia may

be nonspecific, including poor feeding,

lethargy, irritability, cyanosis, temperature
instability, and the overall impression that the
infant is not well.
O Respiratory symptoms of increasing severity
are grunting, tachypnea, retractions, flaring of
the
alae
nasi,
cyanosis,
apnea,
and
progressive respiratory failure.

Pneumonia
O Premature: s of progressive respiratory distress

may be superimposed upon RDS or BPD.

O For infants on mechanical ventilation, the need
to increase ventilator support may indicate
infection.

Intrapartum and Peripartum

Infections
O The maternal history provides important information about maternal

exposures to infectious diseases, bacterial colonization, immunity

(natural

and acquired),

and

obstetric

risk

factors (prematurity,

prolonged ruptured membranes, maternal chorioamnionitis).

O Sexually transmitted infections (STIs) acquired by a pregnant woman

are of particular concern to the fetus and newborn because of the

potential for intrauterine or perinatal transmission.
O All pregnant women and their partners should be queried about a

history of STIs.

CDC Recommendations
1. All pregnant women should be offered voluntary and
confidential HIV testing at the first prenatal visit, as early
in pregnancy as possible.
2. A serologic test for syphilis should be performed on all
pregnant women at the first prenatal visit.
3. Serologic testing for hepatitis B surface antigen
(HBsAg) should be performed at the first prenatal visit,
even if the woman has been previously vaccinated or
tested.

CDC Recommendations
4. A maternal genital culture for C. trachomatis should be performed at the
first prenatal visit.
5. A maternal culture for Neisseria gonorrhoeae should be performed at the
first prenatal visit.
6. All pregnant women at high risk for hepatitis C infection.
7. For asymptomatic women at high risk for preterm delivery, testing may be
considered.
8. Universal screening for rectovaginal GBS colonization of all pregnant women
at 35-37 wk gestation.

Suspected Intrauterine
Infection
O The acronym TORCH refers to toxoplasmosis,

other agents (syphilis, varicella, parvovirus

B19, HIV), rubella, CMV, and HSV. Although
the acronym may be helpful in remembering
some of the etiologic agents of intrauterine
infection, the TORCH battery of serologic tests
has a poor diagnostic yield. Instead, individual
diagnostic studies should be selected for each
etiologic agent under consideration.

Suspected Bacterial or
Fungal Infections

Suspected Bacterial or
Fungal Infections
PNEUMONIA AND PNEUMONITIS
O The differential diagnosis of pneumonitis in
neonates is broad and includes RDS, meconium
aspiration syndrome, persistent pulmonary
hypertension, diaphragmatic hernia, transient
tachypnea of the newborn, congenital heart
disease, and BPD.
O The diagnosis of infectious pneumonia in a
neonate is usually presumptive; microbiologic
proof of infection is generally lacking because
lung tissue is not easily cultured.

Suspected Bacterial or
Fungal Infections
MENINGITIS
O The diagnosis of meningitis is confirmed by
examination of CSF and identification of a
bacterium, virus, or fungus by culture, antigen,
or molecular analysis.
O For term infants with suspected early-onset
sepsis, many clinicians routinely obtain blood
cultures and a complete blood count, because
the etiology of 70-85% of term neonates with
bacterial meningitis may be demonstrated by
blood culture.

Management
O Although it is preferable to have specimens

obtained prior to the initiation of antimicrobial

therapy to optimize recovery of bacterial
organisms,
antimicrobial
therapy
administration should not be delayed for
specimen collection in clinically ill neonates.

O Initial empirical treatment of early-onset bacterial infections of ampicillin

and an aminoglycoside (usually gentamicin), or cefotaxime.

O HAIs acquired in a NICU are more likely to be caused by staphylococci,

various Enterobacteriaceae, Pseudomonas species, or Candida species.

Thus, an antistaphylococcal drug (oxacillin or nafcillin for S. aureus or, more
often, vancomycin for coagulase-negative staphylococci or methicillinresistant S. aureus) should be substituted for ampicillin in a previously
hospitalized neonate.

O A history of recent antimicrobial therapy or the presence

of antibiotic-resistant infections in the NICU suggests the

need for modification of empiric antimicrobial choices.
O When the history or the presence of necrotic skin lesions

suggests Pseudomonas infection, initial therapy should

consist of antipseudomonal agent, such as piperacillin,
ticarcillin,

meropenem,

aminoglycoside.

or

ceftazidime,

and

an

O Treatment of newborn infants whose mothers received antibiotics during

labor should be individualized. If early-onset sepsis is thought to be likely,

treatment of the infant should continue until the infant remains
asymptomatic for 24-72 hr and clinical and laboratory evidence of
recovery is apparent.
O Furthermore, in the context of intrapartum antibiotic use, it is important

to consider that the organism causing infection may be resistant to the

intrapartum therapy, thus influencing selection of empiric antibiotics for
the infant.

O ANTIMICROBIAL RESISTANCE: Although vancomycin

use cannot be avoided in neonatal units where

methicillin-resistant S. aureus is endemic, its use
can be reduced by limiting empirical therapy to
patients with a high suspicion of severe infection
with coagulase negative staphylococci (severely ill
neonate with an indwelling intravascular catheter)
and by discontinuing therapy after 2-3 days when
blood culture results are negative.

O BACTEREMIA: If a neonates condition permits, it is ideal to

obtain a repeat blood culture from the site of the positive

culture at the time of identification of the organism.
O This second culture may be helpful, especially in situations

where the organism isolated would not be susceptible to the

empiric or directed therapy that a neonate is receiving.
O Therapy for most bloodstream infections should be continued

for a total of 7-10 days, or for at least 5-7 days after a clinical
response has occurred.

O PNEUMONIA: A combination of ampicillin and an aminoglycoside or

cefotaxime is appropriate for pneumonia that develops during the 1st 710 days of life.
O Nosocomial pneumonia can be treated empirically with ampicillin or

vancomycin and an aminoglycoside or a third-generation cephalosporin.

O Pseudomonas pneumonia should be treated with an agent to which the

organism is susceptible. Some experts would consider the use of dual

therapy for multidrug resistant organisms; however, the benefits of this
therapy may vary based on host and pathogen. Pneumonia caused by C.
trachomatis usually presents between the 1st and 3rd mo of life and is
usually treated with oral erythromycin.

O MENINGITIS: Empiric antimicrobial therapy for bacterial meningitis

should include ampicillin in doses used for meningitis, unless

staphylococci are likely, in which case vancomycin may be
considered.
O Neonates with shunts may be predisposed to developing meningitis

and ventriculitis attributable to resistant Gram-positive organisms.

O Cefotaxime

or gentamicin in meningitic doses are appropriate

choices for empiric Gram-negative coverage.

Complications and Prognosis

O Complications

of

bacteremic

infections

include

endocarditis, septic emboli, abscess formation, septic

joints with residual disability, and osteomyelitis and
bone destruction. Recurrent bacteremia is rare (<5% of
patients).
O Candidemia may lead to vasculitis, endocarditis, and

endophthalmitis, as well as to abscesses in the kidneys,

liver, lungs, and brain. Sequelae of sepsis may result
from septic shock, DIC, or organ failure.

O Mortality rates from the sepsis syndrome

depend on the definition of sepsis.

O In adults, the mortality rate approaches 50%,
and the rate in newborn infants is probably at
least that high.
O The case fatality rate for neonatal bacterial
meningitis is between 20% and 25%.

Prevention
O Maternal Strategies
a. Vaccination
b. Diet and avoidance of exposure
c. Chemoprophylaxis and insecticide-treated

bed nets (malaria)

d. Timely diagnosis and appropriate early
treatment (Congeital syphilis)

O Antifungal Prophylaxis
a. Prophylactic application of Fluconazole
b. Neonatal practices that may reduce the risks

of invasive candidiasis
O.Other strategies for prevention of healthcare-

associated infections
a. lactoferrin and probiotic supplementation and
the administration of antistaphylococcal
monoclonal antibodies

O Antimicrobial stewardship
O a. This effort is designed to increase clinician awareness

and to improve diagnosis and appropriate treatment of

infection.
O The campaign supports involving infectious disease and

pharmacy

consultants,

antimicrobial

with

the

treating

infections

narrowest

with

spectrum

an
and

discontinuing therapy when adequate therapy has been

administered.

O The end