Harrison's Manual of Medicine

Infective Endocarditis

Infective Endocarditis is a topic covered in the Harrison's Manual of Medicine.

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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 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: Because of their different portals of entry, the causative microorganisms vary among clinical types of endocarditis.
    • In native valve endocarditis (NVE), viridans streptococci, staphylococci, and HACEK organisms (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) enter the bloodstream from oral, skin, and upper respiratory tract portals. Streptococcus gallolyticus subspecies gallolyticus (formerly S. bovis biotype 1) originates from the gut and is associated with polyps or colon cancer.
    • 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) developing within 2 months of surgery is 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 beginning >1 year after valve surgery are caused by the same organisms that cause community-acquired NVE. PVE due to CoNS that presents 2–12 months after surgery often represents delayed-onset nosocomial infection.
    • Cardiovascular implantable electronic device (CIED)–related endocarditis involves the device itself or the endothelium at points of device contact, with 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, especially that involving the tricuspid valve, is 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.
    • About 5–15% of endocarditis cases are culture negative, and one-third to one-half of these cases are due to prior antibiotic exposure. The remainder of culture-negative cases represent infection by fastidious organisms, such as the nutritionally variant bacteria Granulicatella and Abiotrophia spp., HACEK organisms, Coxiella burnetii, Brucella spp., and Tropheryma whipplei.
  • Pathogenesis: Endothelial injury allows direct infection by more virulent pathogens (e.g., S. aureus) or the development of a platelet-fibrin thrombus [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: The clinical syndrome is variable and spans a continuum between acute and subacute presentations. The temporal course of disease is dictated in large part by the causative organism: S. aureus, β-hemolytic streptococci, pneumococci, and Staphylococcus lugdunensis typically present acutely, whereas 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 develops in 30–40% of pts and is usually due to valvular dysfunction.
      • Extension of infection can result in perivalvular abscesses, which in turn may cause intracardiac fistulae. Abscesses may burrow from the aortic root into the ventricular septum and interrupt the conduction system or may burrow through the epicardium and cause pericarditis.
    • Noncardiac manifestations: Arterial emboli, one-half of which precede the diagnosis of endocarditis, are present in 50% of pts, with hematogenously seeded focal infection most often evident in the skin, spleen, kidneys, bones, and meninges.
      • The risk of embolization increases with endocarditis caused by S. aureus, vegetations >10 mm in diameter, and infection involving the mitral valve (particularly the anterior leaflet).
      • Cerebrovascular emboli presenting as stroke or encephalopathy complicate 15–35% of cases, with one-half of these cases preceding the diagnosis of endocarditis.
        • The incidence of stroke decreases dramatically with antibiotic therapy and does not correlate with change in vegetation size; 3% of strokes occur after 1 week of effective therapy, but these late-occurring embolic events do not specifically constitute evidence of failed antimicrobial therapy.
        • Other neurologic complications include aseptic or purulent meningitis, intracranial hemorrhage due to ruptured mycotic aneurysms (focal dilations of arteries at points in the artery wall that have been weakened by infection or where septic emboli have lodged) or hemorrhagic infarcts, seizures, and microabscesses (especially with S. aureus).
      • Immune complex deposition on the glomerular basement membrane causes glomerulonephritis and renal dysfunction, which improve with antibiotic therapy.
      • Nonsuppurative peripheral manifestations of subacute endocarditis (e.g., Janeway lesions, Roth’s spots) are related to duration of infection and are now rare because of early diagnosis and treatment.
    • Manifestations of specific predisposing conditions: Underlying conditions may affect the presenting signs and symptoms.
      • IV drug use: ~50% of endocarditis cases associated with IV drug use are limited to the tricuspid valve and present as fever, faint or no murmur, septic pulmonary emboli (evidenced by cough, pleuritic chest pain, nodular pulmonary infiltrates, or occasional pyopneumothorax), and the absence of peripheral manifestations. Pts with left-sided cardiac infections present with the typical clinical features of endocarditis.
      • Health careassociated endocarditis: Manifestations are typical in the absence of a retained intracardiac device. Endocarditis associated with a transvenous pacemaker or an implanted defibrillator may be associated with a generator pocket infection and result in fever, minimal murmur, and pulmonary symptoms due to septic emboli.
      • PVE: In cases of endocarditis occurring within 60 days of valve surgery, typical symptoms may be masked by comorbidity associated with recent surgery. Paravalvular infection is common in PVE, resulting in partial valve dehiscence, regurgitant murmurs, CHF, or disruption of the conduction system.
  • Diagnosis: A diagnosis of infective endocarditis is established definitively only when vegetations are examined histologically and microbiologically.
    • The modified Duke criteria (Table 80-1) 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.
    • For antibiotic-naïve 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 is 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 echocardiography (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 echocardiography (TEE) detects vegetations in >90% of cases of definite endocarditis and 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 but warrants repetition of the study once or twice in 7–10 days.
      • Routine echocardiography (preferably TEE) is recommended in pts with S. aureus bacteremia.
TABLE 80-1: THE MODIFIED DUKE CRITERIA FOR THE CLINICAL DIAGNOSIS OF INFECTIVE ENDOCARDITISa
Major Criteria
1. Positive blood culture
 Typical microorganism for infective endocarditis from two separate blood cultures
  Viridans streptococci, Streptococcus gallolyticus, HACEK 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 ≥4 separate blood cultures, with first and last drawn at least 1 h apart
  or
 Single positive blood culture for Coxiella burnetii or phase I IgG antibody titer of >1:800
2. Evidence of endocardial involvement
 Positive echocardiogramb
  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)
Minor Criteria
1. Predisposition: predisposing heart conditionsc or injection drug use
2. Fever ≥38.0°C (≥100.4°F)
3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway 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
aDefinite endocarditis is defined by documentation of two major criteria, of one major criterion and three minor criteria, or of five minor criteria. See text for further details.
bTransesophageal echocardiography is required for optimal assessment of possible prosthetic valve endocarditis or complicated endocarditis.
cValvular disease with stenosis or regurgitation, presence of a prosthetic valve, congenital heart disease including corrected or partially corrected conditions (except isolated atrial septal defect, repaired ventricular septal defect, or closed patent ductus arteriosus), prior endocarditis, or hypertrophic cardiomyopathy.
dExcluding single positive cultures for coagulase-negative staphylococci and diphtheroids, which are common culture contaminants, or for organisms that do not cause endocarditis frequently, such as gram-negative bacilli.
Source: Adapted from JS Li et al: Clin Infect Dis 30:633, 2000. With permission from Oxford University Press.

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