Infections of the

Cardiovascular System

Rizalinda Sjahril
Microbiology Department
Faculty of Medicine Hasanuddin University
2010
 Infections of the cardiovascular
system
Myocarditis
Pericarditis
Endocarditis: an infection of the
cardiac endothelium;
macroscopically seen as vegetations.
 Myocarditis
Myocarditis is an inflammation of the myocardium,
caused by:
infectious agents
allergic reaction
drug reaction
associated with systemic inflammatory disease
Acute Myocarditis: symptoms ranges from an
asymptomatic illness with reversible changes to
fulminant myocardial necrosis and death
Chronic myocarditis: lymphocytic infiltration of the
myocardium may cause subacute deterioration of
cardiac function
 Incidence of myocarditis
Incidence is unknown
Children and young adults are more
prevalent than older adults
Major cause of sudden cardiac death
in a person under 40 years old
 Clinical Feature of
Myocarditis
Asymptomatic progressive myocardial
disfunction death
Symptomatic: fever, fatigue, malaise,
chest pain, dyspnea, palpitation,
arthralgia, upper respiratory tract
symptoms

Diagnosis is often difficult! It is suggested

for an acute febrile illness with unexplained
heart failure or malignant arythmia
 Differential Diagnosis
Ischemia
Primary pulmonary
Primary congenital disease
Rheumatologic disease
Endocrinopathies
Electrolyte disturbances
Toxin exposure (ethanol, cocaine,
heavy metals)
 Laboratory values of
myocarditis refer to
Pathology Clinic lectures
Echocardiography
Definitive diagnosis:
endomyocardial biopsy
Microorganisms causing myocarditis

Viral
Bacterial, bacterial toxins (diphteria
toxin)
Fungi
Spirochetes (Borrelia burgdorferi)
Rickettsiae (Rickettsia ricketsii)
Parasites
 Infectious causes of Myocarditis
Region Normal host Immunocompromised
host
Develope Common VIRUSES: Coxsackie A and VIRUSES: HIV, CMV,
d World B, echovirus, CMV, EB Virus, EBV, VZV,
HHV-6, Influenza virus A and adenovirus,
B, adenovirus, Parvovirus, parvovirus
HBV, HCV FUNGI: Candidiasis,
BACTERIA: diphteria, Lyme aspergillosis,
disease, organisms cryptococcosis
associated with IE PARASITES:toxoplasm
PARASITES: American osis, American
Trypanosomiasis, trichinosis trypanosomiasis
Uncomm VIRUSES: Adenovirus, FUNGI:
on Parvovirus, Respiratory histoplasmosis,
syncitial virus, HBV, HCV blastomycosis,
BACTERIA: Staphylococci, coccidioidomycosis,
Streptococci, meningococci, zygomycosis
Salmonellae, listeria,
clostridia, rickettsia,
bartonellosis, ehrlichiosis
Developi VIRUSES: poliovirus, mumps, rubella, arenaviruses,
ng World dengue, rabies, chikungunya, ebola virus, yellow
fever
 Viral myocarditis:
Mild or asimptomatic
Cardiac Signs: damage to the myocard
(cardiomegaly, short breath,
palpitations, arrythmia
Non-cardiac signs: rash, fever, sore
throat
Chest pain
Bacterial myocarditis
 Pericarditis
Pericarditis: injury to the pericardium
causing cellular infiltration, fibrin
deposition and outpouring of pericard
fluid.
The cause of pericarditis:
Infectious agents
Non-infectious
 Infectious causes of pericarditis
Viruses
CMV, Herpes simplex virus, Coxsackie
A, B, echovirus, adenovirus, Influenza,
Mumps, VZV, EBV, HIV
Bacteria
Streptococcus pneumoniae,
Streptococcus spp., Staphylococcus
aureus, Neisseria meningitidis,
Listeria monocytogenes, Hemophilus
influenzae, Francisella tularensis,
Brucella melitensis, Enteric Gram
negative rods, Actinomyces spp.,
Nocardia asteroides, legionella
pneumophila, Tropheryma whippelii,
Salmonella spp., Campylobacter spp.,
Rickettsia/Q fever
Mycobacteria
Mycobacterium tuberculosis,
Mycobacterium chelonae,
Mycobacterium avium complex
Spirochetes
Borrelia burgdorferi
Mycoplasma
Mycoplasma pneumoniae,
Ureaplasma urealyticum, Mycoplasma
hominis
Fungi
Histoplasma capsulatum, Coccidioides
immitis, Cryptococcus neoformans,
Blastomyces dermatitidis, Candida
spp., Aspergillus fumigatus
Parasites
Toxoplasma gondii, Entamoeba
histolityca, Echinococcus granulosus,
Schistosoma spp
 Etiology of large pericardial effusions
Etiology % of 75 diagnosis
Malignancy 27
Viral 16
Collagen vascular 14
disease
Radiation 11
Uremia 11
Mycobacterial 5
Mycoplasma 3
Bacterial 1
Idiopathic 5
other 8

A study by Corey GR, et al (1993) on the etiology of large pericardial effusions

by performing an extensive microbiologic analysis of the pericardial effusions.
Difference in etiologies in different reports indicates variations occur depending
on the sample population and diagnostic strategies
 Bacterial causative of
pericarditis
Bacteria spread to the pericard through:
Hematogenous seeding during bacteremia
Extension of infection from a contiguous focus in the
chest (complication postoperative or post-traumatic)
or from a subdiaphragmatic abscesses
Invasive bacterial infection (staphylococcal
endocarditis)

Pathologic changes in the pericardium which are caused

by immune complex deposition sterile exudates
Most effusions resolve without specific therapy
Most common bacteria: streptococci and staphylococci
 Other causes may be....
Mycoplasma causing pericarditis were
isolated from culture (reported by
Fournier et al, 2001) Treatment is with
doxycyclin after drainage
Mycobacteria is an important cause in
developing countries; 1-8% cases
among pulmonary tuberculosis patients.
Histoplasma capsulatum; 6% of
symptomatic histoplasmosis
 Clinical Features of acute
pericarditis
Chief manifestation: chest pain
precordial/retrosternal, radiates to
the trapezius ridge or neck.
Exacerbated by lying supine,
coughing or deep inspiration.
Relieved when sitting upright or
forward.
Pericardial friction rub:
pathognomonic finding of acute
pericarditis
 Diagnosis of pericarditis
Pericardiocentesis
Pericardial biopsy
Effusion are subjected to microbial analysis: cultures
for aerobic, anaerobic bacteria, detection of viruses,
chlamydiae, mycoplasmas, fungi and mycobacteria

However, since specific etiology of pericarditis is not

apparent, and also their brief and benign course
full diagnostic evaluation becomes not appropriate.
Thus confirming a particular viral agent is not
necessary (costly) and retrospective diagnostic does
not affect treatment.
Management of pericarditis
Hospitalization to relief symptoms,
evaluate diagnosis and observe
complications
Specific treatment depends on the
etiology
To reduce symptoms in idiopathic or
viral pericarditis: Aspirin 2-6g/day or
use other NSAIDS
Appropriate intravenous antibiotics
and surgical drainage
Microbiological methods to diagnose
infection
Bacterial detection:
Culture, isolation and identification of specimen
Serologic examination of serum (Antibody titer)
Molecular Polymerase Chain Reaction (PCR)
Viral detection
Tissue culture
Serologic examination of serum
Molecular (PCR)
Fungal
Culture, isolation and identification
Molecular (PCR)
 Infective Endocarditis
Epidemiology relatively rare lacking report?
Risk factors:
acquired valvular disease (eg. chronic rheumatic heart disease)
cardiac structural abnormalities (eg. artificial (prosthetic) heart
valve, including bioprosthetic and homograft valves, previous
bacterial endocarditis, certain congenital heart diseases, Heart
valve disease that develops after heart transplantation,
Hypertrophic cardiomyopathy (HCM), Mitral valve prolapse with
valve regurgitation (leaking) and/or thickened valve leaflets
immunosuppressed status
prolonged surgery, reoperation
catheter related bacteremia
sternal wound infection
 By echocardiography you will be able
to visualize the heart valves and
deformities.
Understand well the anatomy of the
heart.
Vegetations growing on the valve
that may damage the function of the
valve.
 Predisposing host factor for
IE
At normal condition: Blood is clear of infectious
organisms and endothelium are resistant to
colonization
At times, bacteria or fungi can enter the blood from
other sites of the body or from wound, and it is more
common among intravenous drug users
Preexisting lesions of the layer of endothelial cells
covering the valve or endovascular surfaces (damaged
surfaces) make it susceptible to colonization
Once bacteria/fungi have colonized the heart internal
surface, the immune system cannot clear them off
 Most common causing
microorganism:
Most common cause (80%):
Staphylococcus aureus
Streptococcus spp.
Enterococci

Less common cause:

Coxiella burnetii (Q fever)
Chlamydia spp
Legionella spp
Bartonella spp
 Signs and symptoms
Acute IE: progress over several days to weeks to
valvular destruction, occurring less common caused
mostly by Staphylococcus aureus on a native valve
Bacterial proteases and exoproteins causes rapid
destruction of valve leaflets and development of
abscesses located in the valve ring and the
myocardium
o Fever and murmur 85%
o Hypotension, shock by septic state and by cardiac
failure
o Non specific: fatigue, weight loss, malaise, chills,
night sweats, musculoskleletal aches
 Subacute IE (=SBE) is caused by m.o.
other than Staphylococcus aureus
Occurs from a few days to 5 weeks or
more between the identifiable event
producing bacteremia (e.g. dental
procedure) to the time of diagnosis
Fever
Other signs reflect the existence of
cardiac or peripheral complications
 Categorization of microbial etiologies of

Infective endocarditis

Native Valve endocarditis Prosthetic valve endocarditis

Injecting Drug use Non injecting drug Early Lat

use e

Valvular heart Normal valve

disease

a1
a4
S. aureus
a2 a3 S.epidermidis a4a2 over time
Gram neg. rods
Streptoco S. aureus Gram neg. Rods
Enterococci
cci Enterococci S.Aureus
Candida
Enterococ Streptococci Candida
 Physical findings
Congestive heart failure
Neurologic findings: cerebral emboli,
encephalopathy, mycotic aneurism
leak, meningitis, brain abscess
Chorioretinitis, endophtalmitis
Systemic embolization
 Diagnosis
Precise clinical and microbiologic diagnosis is
mandatory to guide a therapy
The Duke criteria:
A. Microbiologic findings by culture or histologic examinations
in vegetation
Vegetation
Intracardiac abscess
B. Pathologic lesions Echocardiography
vegetation or intracardiac abscess present
Blood cultures
.In case of negative blood culture diagnosis is difficult
.Depends on the nature of causal m.o (blood volume,
methods used, previous antibiotics use, type of m.o)
 Interpretation of the Duke
criteria
Definite pathologic diagnosis: either A or B of the
patologic findings of Dukes criteria
Definite clinical diagnosis: two major criteria, or 1
major and 3 minor or 5 minor criteria
Possible diagnostic: findings consistent with IE,
including 1 major and 1 minor criteria, or 3 minor
criteria
Diagnosis is rejected when:
there is an alternative diagnosis for the clinical
manifestations
resolution of the disease within 4 days of antibiotics
no pathologic evidence upon surgery or autopsy
 Blood culture
Requires +10 ml blood, collected 2-3 times
within 24 hours
Negative culture: previously treated with
antibiotic or possible fastidious m.o. must
try serology, tissue culture (for intracellular
bacteria), immunohistology or PCR detection
Tissue culture is intended for isolation of
Coxiella burnetii, Chlamydia spp., legionella
spp., Bartonella spp..
 Serology tests
Agglutination test for Brucella
melitensis
Indirect fluorescense for L.
pneumophila
ELISA for M. pneumoniae
CF, ELISA and indirect IF for
Chlamydia spp..
 Management:
According to the causing bacteria
Surgery; the indications are:
Refractory cardiac failure
Persistent sepsis caused by a surgically
removable focus or a valvular ring or
myocardial abscess
Persistent life-threatening embolization
 Endarteritis
An inflammation of the arterial wall
Microbial pathogens:
Staphylococcus aureus
Staphylococcus coagulase negative
 Rheumatic fever/Rheumatic Heart
Disease
5 days-10 weeks after pharyngitis
caused by streptococcus pyogenes
Diagnostic criteria: 2 major or 1 major +
2 minor
Major: carditis, polyarthritis migran,
syndenham chorea, nodul subcutaneous,
erythema marginatum
Minor: fever, arthralgia, prolonged PR
interval, increased acute phase reactant
sudden onset of sore throat
pain on swallowing
Strep inf Asymptomatic
fever with symptoms strep infection
headache
red throat/tonsils
abdominal pain, nausea and
vomiting, especially in
children Infection of the pharynx

Infection Ab to strept +
subsided
Persistent
Antibiotics are required eventhough
symptoms have dissappeared
? Strep in the
throat
Hyaluronic acid
capsule

Ongoing Ab producing
Acute rheumatic fever
esp. anti M Ab

Rheumatic Heart Disease &

Post streptococcal Rheumatoid arthritis
streptokinase
streptolysin O (SLO)
DNAase
Hyaluronidase
major surface protein, M
protein

Infectious
materials Humoral immune response
of Group A antibody against Strept components
streptococ
cal
component Autoreactivity in susceptible hosts
s (in particular crossreacting
anti-M protein antibody)

Symptoms of
ARF:
fever
painful, tender, red swollen joints
pain in one joint that migrates to another
one
heart palpitations Acute Rheumatic Fever
chest pain
shortness of breath
skin rashes
fatigue
small, painless nodules under the skin
 REVIEW ON MICROBIAL CAUSE OF
CARDIOVASCULAR INFECTIONS
Streptococcus: major cause of
infections
Morphology:
Coccus, gram positive
On solid media: circular colony, convex,
translucent-opaque, pinpoint size (0.5-1
m)
Requires enriched medium: blood agar
In broth medium, they grow in pairs or
chains
 Classification based on
hemolysis
Hemolytic activity:
hemolytic
hemolytic
hemolitic
 lpha hemolytic: incomplete
hemolysis; green zone around colony
(Hb methHb)
e.g. Streptococcus viridans, usually
nonpathogenic opportunistic, may
cause subacute endocarditis
eta hemolytic: complete hemolysis of blood, clear
zone around colonies, 2-4 x larger the size of colony.
Streptococcus pyogenes (member of GAS = Group A
streptococcus) causing tonsillitis,
bronchopneumonie, scarlet fever, erysipelas, cellulitis,
glomerulonephritis, rheumatic fever
Streptococcus betahemolytic among group B (GBS) are
those found in vaginal mucosa causing puerperal
infection, neonatal meningitis, endocarditis
Streptococcus betahemolytic among group C are those
causing erysipelas, puerperal fever, throat infections
 gamma hemolysis: no hemolytic at
all;
usually non virulent streptococcus
 Virulence factor of
Streptococcus
1. Produces hemolysin alpha and beta
2. Leucocydin to destroy phagocytes
3. Erythrogenic toxin ( in scarlet fever)
4. Hyaluronidase hydrolyse tissue
cement/hyaluronic acid
5. Streptokinase fibrinolysin
6. Nuclease (ribonuklease,
dioksiribonuklease) destroys viscous
tissue debris
 Identification of group A
streptococci
Bacitracin Test
Streak streptococci on agar
Place Bacitracin impregnated filter paper
disc on agar, incubate 24 hours
Group A: observe zone of growth inhibition

Antigenic-antibody reaction
Extract the specimen, react with latex
particle coated with antibody to
streptococci, observe agglutination
 Identification of group B
streptococci
CAMP substance are produced by
group B streptococci that works
sinergically with betahemolysis of
Staphylococcus aureus
Streptococci streaked on to plate,
adjacent to a line streaking of
Staphylococcus aureus, incubate
If it is a Group B streptococcus: an
arrowhead zone of increased hemolysis,
other group shows normal hemolisis
around colony
 Identification of group D
streptococci
Bile esculin test : streptococcus
group D hydrolyses esculin into
6,7dihidroxycumarin, resulting
brownish black on the bile esculin
medium.
Grows in 6.5% NaCl broth. Other
groups do not.
REVIEW ON Staphylococcus
Staphylococcus: bacteria causing infection with
formation of abscesses, pneumoniae,
osteomyelitis, endocarditis, cystitis, pyelonephritis,
food intoxication & septicemia
Morphology:
Colony: circle, white opaque-yellow
Microscopic: irregular clusters, Coccus, gram positive
Major species:
Staphylococcus aureus
Stapylococcus saphrophyticus & S. epidermidis
(normally avirulent, sometimes cause skin lesions and
endocarditis)
 Metabolic end products of
Staphylococci
1. Coagulase (cause clot formation)
2. Leukocydin (lyse white blood cell)
3. Hemolysin
4. Enterotoxin (exotoxins secreted by
some strains of S. aureus)
5. Dnase, lipase, gelatinase non
toxigenic
6. Staphylokinase -- fibrinolysin
 Identification of
Staphylococcus
1. MSA test
Agar medium containing Mannitol and
high Salt concentration
S.aureus: yellow halo forms around the
colony
2. Coagulase test
Coagulase converts fibrinogen to
fibrin
specimen is mixed with citrated-
plasma, will cause coagulation
 3.Dioxyribonuklease test (DNase test)
Agar medium contains DNA
Specimen is spread on agar, hidrolisis of
DNA seen as pink halo around colony
4. Novobiocin sensitivity
Able to distinguish S. epidermidis from S.
saphrophyticus, and S. viridans from other
streptoccocci
Requires Mueller Hinton Agar and
novobiocin disc in sensitivity test.
 S. aureus normal flora in anterior nares and
perineum
S. epidermidis normal found in anterior nares
anterior and the skin
S. saphrophyticus normal in the urinary tract
Other Staphylococcus are common on other parts
of the human body
*all staphs may colonize cathether
*Among staphs only S. aureus produces exotoxins and
able to cause furuncles
*The exotoxins are the exfoliatin pyrogenic and
superantigenik toxins
 Staphylococcus
characteristics
No flagella
Non motile
Non spore producing
Aerob metabolism; can also undergo
facultative anaerob metabolism
Distinguishing Streptococcus from
Staph is by Staphs ability to produce
catalase
S. aureus cell membrane:
composed of a combination of peptidoglycan
and teichoic-ribitol acid molecules, determines
antigenicity and relatively specific for S. aureus
majority of S. aureus possess peptidoglycan
covered by a protein A.
protein A uniquely binds Fc part of IgG
molecule, thus leaving only Fab part of IgG free
to bind with antigen S. aureus becomes
more virulence because of its ability to deter
opsonisation.
The growth of S. aureus
Characteristic growth of S. aureus may be
viewed on medium containing 5% sheeps
blood 5 ml of blood is added into 95ml
autoclaved culture medium named
BLOOD AGAR.
Most S. aureus produces beta hemolysis
around its colony (complete hemolysis)
After incubation overnight whitish colony
formed with a tendency to turn to golden
colour
 HEMOLYSIS & NON
HEMOLYSIS

On this agar cleared area can be Note that the agar medium
seen around the bacterial colony remained red because no
lysis occurred
The difference of S. aureus as
compared to other Staphs:

Coagulase binds prothrombin (non

enzimatic rection) and causes
polimerization of fibrins
COAGULASE /Slide clumping test
S. aureus + plasma clots fibrin
(within hours)
or when concentrated emulsion of
S.aureus + plasma coagulates
readily
 Toxins of S. aureus
1. Alfa toxin
2. Exfoliatin
3. Pyrogenic Toxin Superantigen
Alpha toxin
All S. aureus produce Alpha toxin, except
when it is one of a coagulase-negative strain.
Lyse sitoplasm membrane and form a
transmembrane pore (reviewed in Bhadki S,
etal. Alpha toxin of S. aureus, Microbiol
Review, 1991;55: 733-751)
Alpha toxin acts similar with other cytolysins,
such as the Streptolisin-O, complements and
protein effector of cytotoxic T lymphocyte
Exfoliatin
Degrades intercellular bonds thus
causing the separation of epidermal
layer between the stratum spinosum
and stratum granulosum
Antigenic property:body produces
antibody against expholiatin
Pyrogenic Toxin
Superantigen
PTSAg stimulates a systemic effect when
absorbed from a S. aureus infected site
About 10% S. aureus cannot produce
PTSAg
One strain may produce one or more of
the Sag toxin
Physically, chemically and biologically
the PTSAg of staphylococcus is similar
with that of streptococcus
 References:
1. Medical Microbiology, 3rd edition, Cedric Mims, et al (eds),
Mosby, 2004.
2. Infectious Diseases, 2nd edition, Jonathan Cohen and
William G. Powderly (eds)
3. Zinsser Microbiology, 20th edition
4. Valvular Heart Disease, 3rd edition, Joseph S. Alpert,
James E.Dalen, Rahimtoola Shahbudin H., editors,
Lippincott Williams and Wilkins, 2000
5. Manual of Cardiovascular Medicine, 3rd edition, Brian P
Griffin and Eric J. Topol, editors, Lippincott Williams and
Wilkins, 2009.
6. Bhadki S, etal. Alpha toxin of S. aureus, Microbiol Review,
1991;55: 733-751.