MICROORGANIS

MS CAUSING
CARDIAC
INFECTIONS
Dr.TETTY AMAN NASUTION, MMedSc
Departemen Mikrobiologi FK USU
Medan

CARDITIS
Carditis inflammation of the heart
3 categories:
Pericarditis - Inflammation of the
pericardium

Myocarditis - Inflammation of the heart

muscle

Endocarditis - Inflammation of the

endocardium

Microorganisms Causing
Cardiac Infections
Endocarditis

Myocarditis /
Pericarditis

Streptococcus spp (60-80%)

Staphylococcus spp (20-35%)
Batang Gram Neg. (2-13%)
Bakteri lain2 (5%)
Jamur (2-4%)
Kultur negatif (5-25%)
Virus : Enterovirus, Adenovirus, Herpes virus,
Influenzae virus, Parainfluenza virus.
Bakteri : Staphylococcus aureus,
Streptococcus pneumoniae,
Enterobacteriaceae, Mycobacterium tuberculosis,
Mycoplasma pneumoniae
Fungi

INFEKSI

PENYEBAB TERBANYAK

DIAGNOSE LABORATORIUM

Endocarditis

Streptococcus spp (60-80%)

3 sampel untuk kultur darah yang di-ambil

pada 3 daerah berbeda dilakukan
pengambilan 1 2 jam sebelum pemberian
antimikroba.

Staphylococcus spp (2035%)

Batang Gram Neg. (2-13%)
Bakteri lain2 (5%)
Jamur (2-4%) (Candida)
Kultur negatip (5-25%)

Sampel darah diambil 1 sampel

untuk anaerob dan satu untuk kultur
aerobic masing2 10 20 ml

Myocarditis / Pericarditis
Virus

Enterovirus
Adenovirus
Herpes virus

Pemeriksaan serologic, jika perlu

dikombinasikan dengan kultur dan untuk
PCR.

Influenzae virus
Parainfluenza virus

Bakteri

Staphylococcus aureus
Streptococcus pneumoniae

Pemeriksaan mikroskopis dan kultur. Tes

DNA jika perlu

Enterobacteriaceae
Mycobacterium tuberculosis
Mycoplasma pneumoniae

Tes serologik

INFEKSI

PENYEBAB TERBANYAK

DIAGNOSE LABORATORIUM

Bakteri

Staphylococcus aureus

Pemeriksaan mikroskopis dan kultur. Tes

DNA jika perlu

Streptococcus pneumoniae
Enterobacteriaceae
Mycobacterium tuberculosis
Mycoplasma pneumoniae

Tes serologik

Neicceriae spp

Kultur dan mikroskopis

Gram negative anaerob

Actinomyces & Nocardia
Rickettsia

Tes serologik

Chlamydia trachomatis

Fungi

Candida spp
Aspergillus spp

Mikroskopik dan kultur jamur

Jika perlu PCR

Cryptococcus neoformans

Protozoa
Helminthes

Toxoplasma gondii
Trypanosoma cruzi

Mikroskopik dan kultur jamur

Jikas perlu PCR

Tricinella spiralis

Tes serologik

Kayser, Medical Microbiology, 2005

Sterile Site:

Blood
Cerebrospinal fluid
Pleural fluid
Peritoneal fluid
Pericardial fluid
Surgical aspirate, bone, or joint fluid
Amniotic fluid
Surgically obtained tissue

Non-Sterile Site:
Normal flora:

Respiratory Tract
Ear, Eye, Mouth
Skin ( Wound & Abscess)
Urine (Including Mid-Stream)
Feces

Infective Endocarditis

Febrile illness
Persistent bacteremia
Characteristic lesion of microbial infection of the
endothelial surface of the heart

the vegetation

Variable in size
Amorphous mass of fibrin & platelets
Abundant organisms
Few inflammatory cells

Classification

OLD

Subacute Bacterial Endocarditis

Acute Bacterial Endocarditis

Death in 3-6 months

Death in < 6 weeks

NEW
Native Valve Endocarditis
Prosthetic Valve Endocarditis

Epidemiology Infective
Endocarditis

Adult population :

Rheumatic Heart Disease

Congenital Heart Disease

20 25% of cases of IE in 1970s & 80s

7 18% of cases in recent reported series
Mitral site more common in women
Aortic site more common in men
10 20% of cases in young adults
8% of cases in older adults
PDA, VSD, bicuspid aortic valve (esp. in men>60)

Pediatric population

The vast majority (75-90%) of cases after the neonatal

period are associated with an underlying congenital
abnormality

Aortic valve
VSD
Tetralogy of Fallot

Risk of post-op infection in children with IE is 50%

Characteristics Infective
Endocarditis

Typically involves the valves :

May involve all structures of the heart

Chordae tendinae
Sites of shunting
Mural lesions

Infection of vascular shunts

endarteritis (lesion is the same)

Infective Endocarditis

Pathogenesis
Endothelial damage

Platelet-fibrin thrombi

Microorganism adherence

Pathogenesis
Endocarditis

Exposed extracellular matrix from

vascular damage can bind bacteria
Clotting cascade is stimulated by
exposed extracellular matrix,
which encapsulates the bacteria
within the lesion

Characteristics of Causative
Organisms

Adherence factors critical for growth in the

vegetation
Can adhere to damaged valves (Staph, Strep and
Enterococci have adhesins that mediate
attachment)
Staph adhesin binds fibrinogen and fibronectin
Bacteria trigger tissue-factor production from
local monocytes and induce platelet aggregation
so the organisms become enveloped in the
vegetation
Protection from immune clearance leads to large
numbers of bacteria (109-1010 per g of tissue)

In the vast
majority of
patients,
endocarditis
can be
effectively
treated with
medication
and/or surgery.

Nevertheless,
endocarditis
can cause
serious damage
or even death if
left untreated.

Risk Factors

Structural heart disease

Rheumatic, congenital, aging
Prosthetic heart valves

Intravenous drug abuse

Invasive procedures (?)
Indwelling vascular devices
Other infection with bacteremia (e.g.
pneumonia, meningitis)
History of infective endocarditis

Risk Factor Infective

Endocarditis

Intravenous Drug Abuse

Risk is 2 5% per patient/year
Tendency to involve right-sided valves

Distribution in clinical series

46 78% tricuspid
24 32% mitral
8 19% aortic

Underlying valve normal in 75 93%

S. aureus predominant organism
(>50%, 60-70% of tricuspid cases)

Prosthetic Valve IE

Staphylococci most common

Coagulase negative staphylococci

Enterococcus
Nutritionally variant streptococci
Fungi

Many species of bacteria and fungi

Portals of entry :
= Oral, skin, URI : S. viridans, Staphylococci,
HACEK
= GI : S. bovis (ass. Polyps & colonic tumors)
: Gram negative (Enterobacteriacae)
= GU : Enterococci
= Nosocomial : intravascular catheters : S.aureus

Etiologic agent Infective

Endocarditis
Microbiology

Neonates : S. aureus, coag staph, group B

strep
Older children: 40% strep, S. aureus

Adult Cases :

streptococcus,
staphylococcus,
enterococcus, or
fastidious gram negative cocco-bacillary forms :
Gram negative organisms :
P. aeruginosa most common
HACEK

Etiologic agent Infective

Endocarditis

Staphylococcus aureus (30-40%)

Viridans group streptococci (18%)
Enterococci (11%)
Coagulase-negative staphylococci (11%)
Streptococcus bovis (7%)
Other streptococci (5%)
Non-HACEK Gram negatives (2%)
HACEK Organisms (2%)
Fungi (2%)
Culture negative (2-20%)

Etiologic agent Infective

Endocarditis

Streptococcus viridans accounts for more than 50%

of streptococci causing infective endocarditis,
including S. defectivus and S. adjacens

Enterococci
~ 5% S pneumoniae,
Beta streptococci
rare

Staphylococci: especially post-operatives or in

normal hearts.
Staph. aureus
~ 10-15%
Coagulase-negative
~ 10%

Others -5% Fungi especially Candida

Infective Endocarditis

Gram negative organisms

P. aeruginosa most common
HACEK - slow growing, fastidious
organisms that may need 3 weeks to
grow out of culture

Haemophilus sp.
Actinobacillus
Cardiobacterium
Eikenella
Kingella

Streptococcus sanguis

Like other oral viridans streptococci, S. sanguis

commonly enters the bloodstream following dental
procedures

Adhesins (e.g. SsaB) and the glycocalyx contribute to

infectivity

By facilitating the formation of a vegetation on

damaged heart valves for S. sanguis to colonize, the
glycoprotein PAAP (platelet aggregation-associated
protein) is a particularly important determinant of
virulence that explains why S. sanguis is one of the
most prominent streptococcal species involved in IE

EctoATPase expressed on the surface of S. sanguis

enhances the platelet-aggregating properties of PAAP

Herzberg, M. C. Crit Rev Oral Biol Med 1996;7(3):222-236

DIAGNOSIS IE:
Because the clinical features of the disease can be
quite variable and often nonspecific, diagnosis is
mainly based on laboratory tests.
Blood culture and serologic testing are the most
important.
Always use venous blood to isolate the organism.
A positive blood culture with some or all of the
symptoms listed is needed to obtain the
diagnosis.

Microbiology Diagnostic

BLOOD CULTURE
MULTIPLE BLOOD CULTURES BEFORE EMPIRIC
THERAPY :
If not critically ill

3 blood cultures over 12-24 hour period

? Delay therapy until diagnosis confirmed
If critically ill
3 blood cultures over one hour
No more than 2 from same venipuncture
Relatively constant bacteremia

From another reference :

3 sampel untuk kultur darah yang di-ambil pada 3 daerah berbeda
Dilakukan pengambilan 1 2 jam sebelum pemberian antimikroba

Sampel darah diambil 1 sampel untuk anaerob dan satu untuk aerobic
Masing-masing 10 20 ml (Kayser, Medical Microbiology,
2005)

Intravascular infections

Originate from the cardiovascular system

Cardiac abnormalities, trauma from intraveneous
catheters

Damage cardiac endothelium

Deposition of platelets and fibrin
Transient bacteria

Organisms may stick to and then colonized

Bacterial multiplication (endocarditis)

Extravascular infections

Bacterial entering the blood circulation through the

lymphatic system from another site of infection
Portal of entry

Genitourinary tract 25%

Respiratory tract 20%
Abscesses 10 %
Surgical wound infections 5 %
Biliary tract 5%
Miscellaneous site 10%
Uncertain site 25%

Depend on the site of infection, severity, and organisms

Bacteremia

presence of viable bacteria in the blood

stream
may or may not have symptoms
positive blood culture

Bacteremic episodes

Intermittent bacteremia
bacteria are release into the blood
approximately 45 minutes before a febrile
episode
Common cause of bacteremia

Transient bacteremia
Appear for a brief period following dental,
colonoscopic
Bacterial are indigenous flora

Septicemia or sepsis

Septicemia is bacteremia plus a clinical

presentation of physical signs and symptoms of
the bacteria invasion and toxin production
fever, chills, tachycardia, hypotention, mental confusion

Complication : septic shock, DIC, acute renal

failure

Mortality rate: age, underlying condition and

therapy

Detection of Bacteremia

Specimen collection
Specimen volume
Number of blood culture
Miscellaneous

Specimen collections

Universal precautions
Aseptic techniques

Specimen volume & number of

blood cultures

Bacteremia in adults have a number

of CFU < 30 CFU/ml
Adults 10-20 ml, minimal 10 ml
Children 1-5 ml
Number of blood cultures
1 bottles 80-92%
2 bottles 90-99%
3 bottles 99.6% (be space an hour apart)

Timing of collection
> 1 hr

influx of bacteria

fever, chill

normal host defense mechanisms

bacteria was cleared

Ideal

30 min. before peak temperature

Blood culture media

Trypticase soy broth or Brain heart
infusion broth
Thio broth or thioglycolate broth
Blood : culture media = 1:10 (5:50)

neutralized

bactericidal property of blood

high ratio : prolonged detection time
low ratio : inhibit by serum factors

Anticoagulant

0.025-0.05% Sodium polyanetol

sulphonate (SPS)
Inactivate neutrophils
Inactivate antimicrobial (amonoglycosides,
polymixin)
Inhibit phagocytosis
Inhibit growth of Neisseria gonorrhoea, N.
meningitidis
Prevent by add 1-1.2% gelatin

Heparin, EDTA, and citrate inhibit numerous organisms

Additives
10-20% Hypertonic sucrose or sorbitol
Penicillinase
Antimicrobial-adsorbing (resin):
nonspecific adsorbtion

Incubation at 35-370C and 5% CO2

Ventilation for strictly aerobe
(Pseudomonas, and fungi)

Culture techniques

Conventional culture
Lysis centrifugation
Automated blood culture system

Conventional culture

Culture media
TSB 50 ml, 10 ml
0.025% SPS
1-1.2% gelatin
5% CO2

Blood sample
Adults 5 ml, 3 bottles
Children 1 ml, 2 bottles

Conventional culture

Blind subculture
Blind aerobic subculture : after 24 hrs
Blind anaerobic subculture : after 48 hrs
Early blind subculture : after 6- 18 hrs
Final subculture : after 5-7 days
(bacteria) or 14 days (fungal)

Chocolate agar at 35-370C and 5%

CO2

Conventional culture

Microscopic examination
Grams stain (105
CFU/ml)

Conventional culture

Macroscopic examination
Sign of growth (106-107CFU/ml)
Turbidity
Gas bubbles in the medium
Hemolysis of RBCs
The appearance of small aggregates
of bacterial or fungal growth on the
surface of sedimented RBC

Automated blood culture

system

Automated blood culture

system

BecT/Alert (Organon Teknika)

BACTEC 9240 (Becton Dickinson)

BecT/Alert

Detection unit
- 120, 240 cells

- agitate continuously
- monitored 144 times/days (10 min. interval)

Computer system

BecT/Alert

Culture medium

- 20, 30, 40 ml. Trypticase soy broth

- up to 4 ml. blood (pediatric)
- up to 10 ml. blood (adult)
- anticoagulant = SPS
- supplements with BHI solids and activated
charcoal

Positive

Negative

CO2

CO2 + H2O

semipermeable
membrane
H2CO3

colorimetric sensor
(saturated with water)
H+ + HCO3pH change
color of the sensor change
from dark green to yellow

BACTEC 9240

Continuous monitoring to provide the earliest

possible detection
Resin-based media to neutralize
a ntimicrobials and enhance recovery
Fluorescence-based technology to provide
high sensitivity

Culture Negative IE

Less common with improved blood

culture methods
Special media required :

Longer incubation may be required

Brucella, Mycoplasma, Chlamydia,

Histoplasma, Legionella, Bartonella
HACEK

Coxiella burnetii (Q Fever), Trophyrema

whipplei will not grow in cell-free media

Other microbiologic
methods

PCR

Coxiella burnetii
Tropheryma whipplei
Bartonella henselae

Serology

Coxiella burnetii
Bartonella
Brucella
Legionella
Chlamydophila psittaci

Candidal Endocarditis

Severe condition that has been traditionally associated with

an exceptional high mortality and recurrence rates.
Both native and prosthetic valves may be affected.
Combining medical with surgical interventions, the hospital
survival rates have been commonly below 50%.
The highest long term survival rate is 67%
Open heart surgery is one of the most frequent risk factors
for fungal endocarditis, with a rate of 0.23% to 1% of all
cardiac surgeries.
Fungal prosthetic valve endocarditis has been reported
to be 9.6% and 4.3%, respectively.
Intravenous drug abusers have the highest rates of fungal
endocarditis. Candida spp. account for between 50 and 60%
of cases
Neonates may develop endocarditis as part of the picture of
disseminated neonatal candidiasis . Candida spp. causes all of
the infections.

Candidal Pericarditis

Rare but serious condition that can lead to

severe sepsis, cardiac tamponade and death if
not diagnosed and treated promptly
Candidal pericarditis may occur in relation to
obvious hematogenous seeding from
invasive candidiasis
Candida albicans is the most frequent species,
followed by C. tropicalis.
Of the 26 cases reviewed by Rabinovici et al.
only 18 had species identification.
Of these 78% of them were caused by Candida
albicans.

Candidal Endocarditis (laboratory

diagnostic)
Blood cultures. The sensitivity of blood cultures to
detect invasive candidiasis is generally low. However,
the intravascular site of this infection changes that
rule.

Rates of 83 to 95% of positive blood cultures for

Candida spp. have been reported in reviews of fungal
endocarditis
In the review by Nguyen et al. of 18 prospectively
identified cases of candidal prosthetic valve
endocarditis, all patients had several positive blood
cultures.
The mean and median number of positive blood
cultures for this group were 7 and 5 respectively

Candida species and Candida Pericarditis

Candida albicans is the most frequent species, followed by C.
tropicalis.
Specific Diagnostic Strategies
To make the diagnosis of Candida pericarditis, one should :
Recognize the patient populations at risk,
Perform an echocardiogram when suspecting the picture,
Perform a pericardiocentesis,
Isolate Candida from the pericardial fluid or tissue ,
and
Ideally, have a histopathologic confirmation of yeast forms
in pericardial tissue.
Therapies
Treating Candida pericarditis requires an aggressive
approach that combines surgical and medical treatment .
Prolonged courses of amphotericin B but the precise
length of therapy is not defined

Less prevalent causative agents

include

Other bacteria
The HACEK Group
Haemophilus species, Actinobacillus
actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens, and Kingella
species
Usual bacterial causes
Bacillus cereus, Clostridium perfringens,
Mycobacterium tuberculosis, Nocardia
asteroides, Coxiella burnetii, etc.
Fungi
Candida and Aspergillis species

Pericarditis

An inflammation of the pericardium, the

thin, fluid-filled sac surrounding the heart. It
can cause severe chest pain (especially upon
taking a deep breath) and shortness of
breath.

Also called: Adhesive Pericarditis,

Postmyocardial Pericarditis, Acute
Pericarditis, Bacterial Pericarditis,
Polyserositis, Chronic Pericarditis,
Constrictive Pericarditis.

Most patients
with
pericarditis
also have
some fluid in
the
pericardial
sac.

Pericarditis

Often local manifestation of another

disease
May present as:
Acute pericarditis
Pericardial effusion
Constrictive pericarditis

63

Acute Pericarditis

Acute inflammation of the

pericardium
Cause often unknown, but commonly
caused by infection, uremia,
neoplasm, myocardial infarction,
surgery or trauma.
Membranes become inflamed and
roughened, and exudate may develop
64

Pericardial effusion

Accumulation of fluid in the

pericardial cavity
May be transudate
May be exudate
May be blood

Not clinically significant other than to

indicate underlying disorder, unless:
Pressure becomes sufficient to cause
cardiac compression cardiac
tamponade
65

Constrictive (chronic)
pericarditis

Years ago, synonymous with T.B.

Today, usually idiopathic, or
associated with radiation exposures,
rheumatoid arthritis, uremia, or
coronary bypass graft

66

Myocarditis

Also called: Fulminant Myocarditis, Acute

Myocarditis

An uncommon inflammation of the heart

muscle (myocardium).
can be caused by infectious agents,
toxins, drugs or for unknown reasons.
may be localized to one area of the heart, or
it may affect the entire heart.
Approximately 50% of the time, myocarditis
is classified as idiopathic although a viral
etiology is often suspected but unproved.

Myocardial damage mechanisms

Direct toxic action of the infectious

agent on the myocyte (C. Chauvoei,
L. monocytogenes)
Indirectly, through circulating toxic
products that are released from an
overwhelming infection (sepsis)
Immune-mediated mechanisms,
cellular or antibody-mediated
(chronic infections)

Pathogenesis

Three phases:
Viral Replication
Autoimmune injury
Dilated cardiomyopathy

Etiology Agents of
Myocarditis

Viral - Enterovirus, coxsackie B, adenovirus, influenza,

cytomegalovirus, poliomyelitis, Epstein-Barr virus, HIV-1, viral
hepatitis, mumps, rubeola, varicella, variola/vaccinia,
arbovirus, respiratory syncytial virus, herpes simplex virus,
yellow fever virus, rabies
Rickettsial - Scrub typhus, Rocky Mountain spotted fever, Q
fever
Bacterial - Diphtheria, tuberculosis, streptococci,
meningococci, brucellosis, clostridia, staphylococci,
melioidosis, Mycoplasma pneumoniae, psittacosis
Spirochetal - Syphilis, leptospirosis / Weil disease, relapsing
fever/Borrelia, Lyme disease
Fungal - Candidiasis, aspergillosis, cryptococcosis,
histoplasmosis, actinomycosis, blastomycosis,
coccidioidomycosis, mucormycosis

Viruses :

Etiology Agents of
Myocarditis

Bacteria :

Enteroviruses
Influenza A and B
Adenovirus
Herpes
HIV

Beta-hemolytic Streptococcus
Corynebacterium diphtheria
Borrelia burgdorferi
Enterococcus spp
Chlamydia psittaci
Neisseria meningitidis
Mycoplasma pneumonia
Staphylococcus aureus

pto

Viral Myocarditis

Coxsackievirus A9 is a self-limiting myocarditis,

whereas coxsackievirus B3 causes severe
myocarditis resulting in a high mortality rate.

Approximately 50% of the time, myocarditis is

classified as idiopathic, although a viral
etiology is often suspected but unproved
Viral - Enterovirus, coxsackie B, adenovirus,
influenza, cytomegalovirus, poliomyelitis,
Epstein-Barr virus, HIV-1, viral hepatitis,
mumps, rubeola, varicella, variola/vaccinia,
arbovirus, respiratory syncytial virus, herpes
simplex virus, yellow fever virus, rabies

Viral Myocarditis
Viral myocarditis results when the muscles in the
walls of heart become infected with a virus.
Enteroviruses and adenoviruses are the primary
causative agents of viral myocarditis.
Symptoms
Fever
Cough
Nausea
Vomiting
Myalgia
Arthralgia
Palpitation
Heart failure (in severe cases)

Candidal Myocarditis

Hematogenous seeding of Candida

into the myocardium was frequently
found in the early autopsy reviews of
patients dying with systemic invasive
candidiasis.

The lack of inflammatory response is

most notable in immunosuppressed
patients

Chlamydia pneumoniae as an emerging

risk factor in cardiovascular disease.

Seroepidemiologic studies have associated C. pneumoniae antibody with

coronary artery disease, myocardial infarction, carotid artery disease, and
cerebrovascular disease.
The association of C. pneumoniae with atherosclerosis is corroborated by
the presence of the organism in atherosclerotic lesions throughout the
arterial tree and the near absence of the organism in healthy arterial
tissue.
C. pneumoniae has also been isolated from coronary and carotid
atheromatous plaques.

Compelling evidence of the association between C. pneumoniae and

atherosclerosis has been obtained by polymerase chain reaction (PCR),
immunocytochemical (ICC) staining, and electron microscopy, which have
detected C. pneumoniae in atherosclerotic lesions

A causative role of C. pneumoniae infection in cardiovascular disease has

not yet been firmly established.
However, the high frequency of infection found in human atherosclerotic
tissue in comparison to normal tissue, the induction and progression of
atherosclerotic-like inflammatory changes in infected animal models of
atherosclerosis, and the early results from antichlamydial intervention
studies in humans are consistent with a causative role of C. pneumoniae in
the disease process.

Infection, inflammation
and atherosclerosis

C. pneumoniae, H. pylori,
Porphyromonas gingivalis,
Cytomegalovirus, Herpes simplex
virus, Hepatitis A, B, and C virus
linked with an increased risk of
cardiovascular diseases
Pro inflammatory effects of infection
increased CRP, cytokines

MYOCARDIAL INFARCTION

Myocardial infarction can occur in the

absence of the common risk factors such as
hypercholesterolemia, diabetes mellitus or
cigarette smoking.
The sequence of events that leads to acute
myocardial infarction includes atherosclerotic
plaque formation, plaque rupture, coronary
artery thrombosis and coronary occlusion.
Anything that leads to plaque rupture can
result in myocardial infarction.

ETIOLOGY:
Chylamydia pneumoniae, a Gram-,
pleomorphic, obligate intracellular parasite.

DIAGNOSIS MYOCARDIAL
INFARCTION :
1.Non-specific indices of tissue necrosis and inflammation
a.Polymorphonuclear leukocytosis
b.Erythrocyte sedimentation rate that rises more
slowly
than the WBC count
2.The electrocardiogram
3.Serum enzyme changes
a.Creatine phosphokinase (CK)
b.Lactic dehydrogeinase (LDH)
4.Cardiac imaging
5.Presence of chlamydia in the plaque
6.Presence of antibiodies to C. pneumoniae

Cardiovascular Syphilis

Although morphological involvement of the

cardiovascular system occurs in 80% of
cases of tertiary syphilis only about 10% of
these are manifested clinically.

The spirochetes evoke endarteritis in the

vasa vasorum of the aorta and coronary
ostia.
Clinical manifestations occur in 15 - 30
years after infection.

1 Aortic aneurysm
2 Aortic Valve Disease
3 Coronary Artery Disease

Mucous membrane or other

colonized

Valvular endothelium
tissue
trauma
turbulence
metabolic
Platelet-fibrin deposition

Trauma

Nonbacterial thrombotic
endocarditis (NBTE)
Ab

Bacteremia
Complement
Adherence

Colonization
bacterial division
fibrin depositon
platelet aggregation
extracellular proteases
neutrophils protection
mature vegetation