• Prototype lesion is the vegetation, which is a mass of platelet, fibrin, microorganisms and

inflammatory cells

• Develops on damaged valves, low pressure side of VSD, intracardiac devices and damaged
endocardium

Classified into:

• Acute endocarditis is a febrile illness that rapidly damages cardiac structures, seeds extracardiac
sites hematogenously, and can progress to death within weeks

• Subacute endocarditis follows an indolent course, rarely causes metastatic infection, and
progresses gradually unless complicated by a major embolic event or a ruptured mycotic
aneurysm

EPIDEMIOLOGY

• In developed countries, the incidence of endocarditis ranges from 4 to 7 cases per 100,000
population per year, with higher rates among the elderly

• Predisposing conditions include association with health care, congenital heart disease, illicit IV
drug use, degenerative valve disease, and the presence of intracardiac devices

• Chronic rheumatic heart disease is a risk factor in low-income countries

• Of endocarditis cases, 16-30% involve prosthetic valves, with the greatest risk during the first
6-12 months after valve replacement

ETIOLOGY AND MICROBIOLOGY

• Native-valve endocarditis (NVE)

◦viridans streptococci, staphylococci, and HACEK organisms (Haemophilus spp.,

Aggregatibacter spp., Cardiobacterium spp., Eikenella corrodens, and Kingella kingae)

◦Enter the bloodstream from oral, skin, and upper respiratory tract portals

• Health care-associated NVE

◦Frequently due to Staphylococcus aureus, coagulase-negative staphylococci (CONS), and

enterococci

◦May have a nosocomial onset (55%) or a community onset (45%) in pts who have had
extensive contact with the health care system in the preceding 90 days.

• Prosthetic-valve endocarditis (PVE)

◦Within 2 months of surgery, due to intraoperative contamination or a bacteremic

postoperative complication and is typically caused by CONS, S. aureus, facultative gram-
negative bacilli, diphtheroids, or fungi

◦Cases seen>1 year after valve surgery are caused by the same organisms that cause
community-acquired NVE

• Cardiovascular implantable electronic device (CIED)- related endocarditis

◦Involves the device itself or the endothelium at points of device contact

◦Occasional concurrent aortic or mitral valve infection

◦One-third of cases of CIED endocarditis present within 3 months after device implantation or
manipulation, one-third present at 4-12 months, and one-third present at >1 year

◦S. aureus and CoNS (often methicillin-resistant strains) cause the majority of cases

• Endocarditis occurring among IV drug users

◦Mainly involving the tricuspid valve

◦Commonly caused by S. aureus (often a methicillin-resistant strain)

◦Left-sided valve infections among IV drug users are caused by Pseudomonas aeruginosa
and Candida, Bacillus, Lactobacillus, and Corynebacterium spp. in addition to the usual
 causes of endocarditis

• Culture negative endocarditis,

◦Accounts for 5-15% of cases

◦One-third to one-half of these cases due to prior antibiotic exposure

◦infection by fastidious organisms, such as the nutritionally variant bacteria Granulicatella and
Abiotrophia spp., HACEK organisms, Coxiella burneti,

PATHOGENESIS

• Endothelial injury allows direct infection by more virulent pathogens (e.g., S. aureus) or the
development of a platelet-fibrin thrombus (a condition referred to as nonbacterial thrombotic
endocarditis (NBTE]) that may become infected during transient bacteremia

• NBTE arises from cardiac conditions (e.g., mitral regurgitation, aortic stenosis, aortic
regurgitation), hypercoagulable states (giving rise to marantic endocarditis, which consists of
uninfected vegetations), and the antiphospholipid antibody syndrome

• After entering the bloodstream, organisms adhere to the endothelium or sites of NBTE via surface
adhesin molecules

• The clinical manifestations of endocarditis arise from cytokine production, damage to intracardiac
structures, embolization of vegetation fragments, hematogenous infection of sites during
bacteremia, and tissue injury due to the deposition of immune complexes

CLINICAL MANIFESTATIONS

• Variable and spans a continuum between acute and subacute presentations

◦ S. aureus, 6-hemolytic streptococci, pneumococci, and Staphylococcus lugdunensis

typically present acutely

◦viridans streptococci, enterococci, CONS (other than S, lugdunensis), and the HACEK group
typically present subacutely

• Constitutional symptoms: generally nonspecific, but may include fever, chills, weight loss,
myalgias, or arthralgias

• Cardiac manifestations:

◦Heart murmurs, particularly new or worsened regurgitant murmurs, are ultimately heard in
85% of pts with acute NVE.

◦CHF in 30-40% , usually due to valvular dysfunction.

◦Extension of infection with resultant perivalvular abscesses, intracardiac fistulae, interruption

of the conduction system, pericarditis

• Noncardiac manifestations:

◦ one-half of which precede the diagnosis of endocarditis

• Arterial emboli (50% of pts), with hematogenously seeding of infection

◦Often evident in the skin, spleen, kidneys, bones, and meninges.

◦Risk of embolization highest in S. aureus, mobile vegetations >10 mm in diameter, and

infection involving the mitral valve (particularly the anterior leaflet)

• Cerebrovascular emboli (15-35%), presenting as stroke or encephalopathy

◦Incidence decreases with antibiotic therapy

◦Other neurologic complications: aseptic or purulent meningitis, intracranial hemorrhage due

to ruptured mycotic aneurysms or hemorrhagic infarcts, seizures, and microabscesses (S,
aureus)

• Immune complex deposition on the glomerular basement membrane

◦causes glomerulonephritis and renal dysfunction improve with antibiotic therapy

• Manifestations of specific predisposing conditions:

Underlying conditions may affect the presenting signs and symptoms

• Iv drug use:

◦50% of involvement are to the tricuspid valve

◦present as fever, faint or no murmur, septic pulmonary emboli (evidenced by cough, pleuritic
chest pain, nodular pulmonary infiltrates, or occasional empyema or pyopneumothorax), and

◦the absence of peripheral manifestations

• Health care-associated endocarditis:

◦Those associated with a transvenous pacemaker or an implanted defibrillator may have

generator pocket infection, with fever, minimal murmur, and pulmonary symptoms due to
septic emboli

• PVE:

◦occurring within 60 days of valve surgery typical symptoms may be masked by comorbidity
associated with recent surgery

DIAGNOSIS

• Definitive diagnosis only when vegetations are examined histologically and microbiologically

• The modified Duke criteria constitute a highly sensitive and specific diagnostic schema that
emphasizes the roles of bacteremia and echocardiographic findings

• A clinical diagnosis of definite endocarditis requires fulfillment of two major criteria, one major
criterion plus three minor criteria, or five minor criteria

• A diagnosis of possible endocarditis requires documentation of one major criterion plus one minor
criterion or three minor criteria

Major Criteria

1. Positive blood culture

• Typical microorganism for infective endocarditis from two separate blood cultures Viridans
streptococci, Streptococcus gallolyticus, HACK group organisms, Staphylococcus aureus, or
Community-acquired enterococci in the absence of a primary focus,

or

• Persistently positive blood culture, defined as recovery of a microorganism consistent with

infective endocarditis from:

◦Blood cultures drawn >12 h apart; or

◦All of 3 or a majority of 24 separate blood cultures, with first and last drawn at least 1h apart

Or

◦Single positive blood culture for Coxiella burnetii or phase I lgG antibody titer of >1:800

2. Evidence of endocardial involvement

• Positive echocardiogram

• Oscillating intracardiac mass on valve or supporting structures or in the path of regurgitant jets or
in implanted material, in the absence of an alternative anatomic explanation,

or

• Abscess,

or

• New partial dehiscence of prosthetic valve,

or

• New valvular regurgitation (increase or change in preexisting murmur not sufficient)

• Definite endocarditis is defined by documentation of two major criteria, of one major criterion and
three minor criteria, or of five minor criteria.

Minor Criteria

1. Predisposition: predisposing heart conditions or injection drug use

2. Fever 238.0°C (2100.4°F)

3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm,
intracranial hemorrhage, conjunctival hemorrhages, Jane way lesions

4. Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth's spots, rheumatoid factor

5. Microbiologic evidence: positive blood culture but not meeting major criterion, as noted
previously, d or serologic evidence of active infection with an organism consistent with infective
endocarditis

ORGANISM-SPECIFIC THERAPIES

• Endocarditis due to group B, C, or G streptococci should be treated with the regimen

recommended for relatively penicillin-resistant streptococci

• Killing of enterococci requires the synergistic activity of a cell wall- active agent and an
aminoglycoside (gentamicin or streptomycin) to which the isolate does not exhibit high-level
resistance. If toxicity develops after 2-3 weeks of treatment, the aminogiycoside can be
discontinued in pts who have responded satisfactorily

• For antibiotic-naive pts, three 2-bottle sets of blood culture samples- separated from one another
by at least 2 h- should be obtained from different sites within the first 24 h.

• If blood cultures are negative after 48-72 h, two or three additional sets of samples should be
cultured

• Serology

• Helpful in implicating Brucella, Bartonella, Legionella, Chlamydia psittaci, or C. burnetii in

endocarditis

• Examination of the vegetation by histology, culture, direct fluorescent antibody techniques, and/or
PCR may be helpful in identifying the causative organism in the absence of a positive blood
culture

• Echocardiography should be performed to confirm the diagnosis, to verify the size of

vegetations, to detect intracardiac complications, and to assess cardiac function

• Transthoracic Echocardiograpiy (TTE) does not detect vegetations <2 mm in diameter, is not
adequate for evaluation of prosthetic valves or detection of intracardiac complications, and is
technically inadequate in 20% of pts because of emphysema or body habitus; however, TTE may
suffice when pts have a low pretest likelihood of endocarditis

• Transesophageal echocardiograph (TEE) detects vegetations in >90% of cases of definite

endocarditis, is optimal for evaluation of prosthetic valves and detection of abscesses, valve
perforation, or intracardiac fistulas

• When endocarditis is likely, a negative TEE result does not exclude the diagnosis, warrants
repetition of the study once or twice within 7-10 days

• Routine echocardiography (preferably TEE) is recommended in pts with S, aureus bacteremia.

TREATMENT

ANTIMICROBIAL THERAPY

• Antimicrobial therapy must be bactericidal and prolonged

‣ Blood cuitures should be repeated until sterile, Resuits should be rechecked if there is
recrudescent fever and at 4-6 weeks after therapy to document cure

‣ If pts are febrile for 7 days despite antibiotic therapy, an evaluation for paravalvular or
extracardiac abscesses should be performed

• Pts with acute endocarditis require antibiotic treatment as soon as three sets of blood culture
samples are obtained, but pts with subacute disease who are clinically stable should have
antibiotics withheld until a diagnosis is made

• Pts treated with vancomycin or an aminoglycoside should have serum drug levels monitored.
Periodic tests to detect renal, hepatic, and/or hematologic toxicity should be performed

Antimicrobial treatment of common causative organisms in IE

Duration

Duration

I I l
Organisms Antimicrobial
Dose

NV PV

Viridans streptococci & streptococci bovis

MIC <0.1 mg/L

B.enzy| Pen IV &
1.2 g 6 times daily
4 wKS
6 WkS

Gentamycin IV 1mg/kg 2-3 times daily

2 wks 2 wkS

MIC> 0.1 to > Benzyl Pen IV &

1.2 g 6 times daily
4 wkS
6 wks

0.5 mg/L Gentamycin IV

1mg/kg 2-3 times daily 2 wks 4-6 wks

Benzyl Pen IV &

1.2 g 6 times daily
4 WKS
6 wks

Gentamycin IV
1mg/kg 2-3 times daily
4 wkS
4-6 wkS

Enterococci

Ampicillin-
Ampicillin IV &
2 g 6 times daily
4 wkS
6 wkS

sensitive Gentamycin IV 1 mg/kg 2-3 times daily 4 wkS 6 wkS

4 wKS
6 wks

Ampicillin-
Vancomycin IV &
1 g twice daily

resistant
Gentamycin IV
1 mg/kg 2-3 times daily 4 wks 6 wks

Staphylococci

Penicillin- •
Benzyl pen IV 1.2 g 6 times daily 4 wkS 6 wks
sensitive

Penicillin-

resistant
FlucloxacillinIV 2 g 6 times daily 4 wkS
6 wks
Methicillin-

sensitive

Penicillin- Vancomycin IV 1 g twice daily

4 wks
6 WkS

resistant
&
1 mg/kg 2-3 times
4 WKS
6 wks
Methicillin- Gentamycin IV daily

resistant

Short course treatment of S.viridans/bovis endocarditis (2 wks)

• Native valve infection

• MIC </= 0.1 mg/L

• No adverse prognostic factors (HF, AR, conduction defect)

• No e/o thromboembolic disease

• No vegetations > 5 mm diameter

• Clinical response within 7 d

OUTCOME

• Death and other poor outcomes are related not to failure of antibiotic therapy but rather to
interactions of comorbidities and endocarditis-related end-organ complications

• Survival rates are 85-90% for NVE due to viridans streptococci, HACEK organisms, or
enterococci as opposed to 55-70% for NVE due to S. aureus in pts who are not IV drug users

• PVE beginning within 2 months of valve replacement results in mortality rates of 40-50%,
whereas rates are only 10-20% in later-onset cases

PREVENTION

The American Heart Association and the European Society of Cardiology have narrowed
recommendations for antibiotic prophylaxis, limiting its use to pts at highest risk of severe morbidity
and death from endocarditis

• Prophylaxis is recommended only for those dental procedures involving manipulation of gingival
tissue or the periapical region of the teeth or perforation of the oral mucosa (including respiratory
tract surgery)

• Prophylaxis is not advised for pts undergoing Gl or genitourinary tract procedures unless the
genitourinary tract is infected

High-Risk Cardiac Lesions for Which Endocarditis Prophylaxis Is Advised before Dental
Procedures

• Prosthetic heart valves

• Prior endocarditis

• Unrepaired cyanotic congenital heart disease, including palliative shunts or conduits

• Completely repaired congenital heart defects during the 6 months after repair

• Incompletely repaired congenital heart disease with residual defects adjacent to prosthetic
material

• Valvulopathy developing after cardiac transplantation

Antibiotic Regimens for Prophylaxis of Endocarditis in Adults with High-Risk Cardiac Lesions

A. Standard oral regimen

Amoxicillin; 2 g PO 1 h before procedure

B. Inability to take oral medication

Ampicillin: 2 g IV or IM within 1 h before procedure

C. Penicillin allergy

1. Clarithromycin or azithromycin; 500 mg PO 1 h before procedure

2. Cephalexinc: 2 g PO 1 h before procedure

3, Clindamycin; 600 mg PO 1 h before procedure

D. Penicillin allergy, inability to take oral medication

1. Cefazolinc or ceftriaxonec: 1 g IV or IM 30 min before procedure

2. Clindamycin: 600 mg /V or IM 1 h before procedure

Dosing for children: for amoxicillin, ampicillin, cephalexin, or cefadroxil, use 50 mg/kg PO;
cefazolin, 25 mg/kg IV; clindamycin, 20 mg/kg PO or 25 mg/kg IV; clarithromycin, 15 mg/kg PO; and
vancomycin, 20 mg/kg IV