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.

In developed countries, the incidence of endocarditis ranges from 2.6 to 7.0 cases per 100,000 population per year. Predisposing conditions include congenital heart disease, illicit IV drug use, degenerative valve disease, intracardiac devices, and health care-associated infections. The incidence of endocarditis is increased among the elderly and among pts with prosthetic heart valves. The risk of endocarditis is greatest during the first 6 months after valve replacement.

The causative microorganisms vary, in part because of different portals of entry. In native valve endocarditis (NVE), viridans streptococci, staphylococci, and HACEK organisms (Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) enter the bloodstream from oral, skin, and upper respiratory tract portals, respectively. Streptococcus bovis originates from the gut and is associated with colon polyps or cancer. Enterococci originate from the genitourinary tract. Nosocomial endocarditis, frequently due to Staphylococcus aureus, arises most often from bacteremia related to intravascular devices. 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 coagulase-negative staphylococci (CoNS), S. aureus, facultative gram-negative bacilli, diphtheroids, or fungi. At 1 year after valve surgery, endocarditis is caused by the same organisms that cause community-acquired NVE. IV drug users are particularly prone to tricuspid valve endocarditis caused by S. aureus (often a methicillin-resistant strain); they are also at risk for left-sided endocarditis caused by S. aureus, Pseudomonas aeruginosa, or Candida spp. Fastidious organisms such as the nutritionally variant bacteria Granulicatella and Abiotrophia, HACEK bacteria, Bartonella spp., Coxiella burnetii, Brucella spp., and Tropheryma whipplei can cause culture-negative endocarditis. β-Hemolytic streptococci, S. aureus, and pneumococci typically cause acute endocarditis, while viridans streptococci, enterococci, CoNS, and HACEK organisms usually cause subacute disease.

If endothelial injury occurs, direct infection by pathogens such as S. aureus can result, or an uninfected platelet-fibrin thrombus may develop and become infected during transient bacteremia. The vegetation (Fig. 87-1) is the prototypic lesion at the site of infection: a mass of platelets, fibrin, and microcolonies of organisms, with scant inflammatory cells.

Figure 87-1
Vegetations (arrows) due to viridans streptococcal endocarditis involving the mitral valve.

The clinical syndrome is variable and spans a continuum between acute and subacute presentations.

Cardiac Manifestations

• Heart murmurs, particularly new or worsened regurgitant murmurs, are ultimately heard in 85% of pts with acute NVE.
• Congestive heart failure (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 fistulae from the aortic root into cardiac chambers or may burrow through epicardium and cause pericarditis.
• Heart block may result when infection extends into the conduction system.
• Emboli to a coronary artery may result in myocardial infarcts.

Noncardiac Manifestations

• Hematogenous bacterial seeding (e.g., to the spleen, kidneys, and meninges) can cause abscesses in noncardiac tissues.
• Arterial emboli of vegetation fragments lead to infection or infarction of remote tissues such as the extremities, spleen, kidneys, bowel, or brain. Emboli most commonly arise from vegetations >10 mm in diameter and from those located on the mitral valve. With antibiotic treatment, the frequency of emboli decreases from 13 per 1000 pt-days during the first week of infection to 1.2 per 1000 pt-days during the third week.
• Neurologic complications are seen in up to 40% of pts and include embolic stroke, 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, encephalopathy, and microabscesses.
• Renal infarcts cause flank pain and hematuria without renal dysfunction.
• Immune complex deposition causes glomerulonephritis and renal dysfunction.
• Peripheral manifestations such as Osler's nodes, subungual hemorrhages, Janeway lesions, and Roth's spots are nonsuppurative complications seen in prolonged infection and are now rare because of early diagnosis and treatment.

Tricuspid Valve Endocarditis
This condition is associated with fever, faint or no heart murmur, and prominent pulmonary findings such as cough, pleuritic chest pain, and nodular pulmonary infiltrates.

Health Care-Associated Endocarditis
Manifestations depend on the presence or absence of a retained intracardiac device. For example, transvenous pacemaker lead-related endocarditis may be associated with generator pocket infection and results in fever, minimal murmur, and pulmonary symptoms due to septic emboli.

Paravalvular Infection
This condition is common in PVE, resulting in partial valve dehiscence, regurgitant murmurs, CHF, or disruption of the conduction system.

• The Duke criteria (Table 87-1) constitute a sensitive and specific diagnostic schema. Definite endocarditis is defined by 2 major, 1 major plus 3 minor, or 5 minor criteria. Possible endocarditis is defined by 1 major plus 1 minor criterion or by 3 minor criteria.
• If blood cultures are negative after 48-72 h, 2 or 3 additional cultures should be performed, and the laboratory should be asked for advice regarding optimal culture techniques.
• Serology is helpful in the diagnosis of Brucella, Bartonella, Legionella, or C. burnetii endocarditis.
• 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 and is not adequate to evaluate prosthetic valves or to detect intracardiac complications; however, TTE may be used in pts with a low pretest likelihood of endocarditis (<5%). In other pts, transesophageal echocardiography (TEE) is indicated. 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.
• Other laboratory studies should be performed-e.g., a complete blood count, creatinine measurement, liver function tests, chest radiography, and electrocardiography. The erythrocyte sedimentation rate, C-reactive protein level, and circulating immune complex titer are typically elevated.

ANTIMICROBIAL THERAPY
Antimicrobial therapy must be bactericidal and prolonged. See Table 87-2 for organism-specific regimens. Most pts defervesce within 5-7 days. Blood cultures should be repeated until sterile, and results 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 stable pts with subacute disease should have antibiotics withheld until a diagnosis is made. Pts treated with vancomycin or an aminoglycoside should have serum drug levels monitored. Tests to detect renal, hepatic, and/or hematologic toxicity should be performed periodically.
• Selection of optimal treatment for streptococcal endocarditis requires determination of the minimal inhibitory concentration (MIC) of penicillin for the causative isolate. Two-week regimens should not be used for complicated NVE or for PVE. Groups B, C, and G streptococcal endocarditis should be treated with the regimen recommended for relatively penicillin-resistant streptococci (Table 87-2).
• Enterococci require the synergistic activity of a cell wall-active agent and an aminoglycoside for killing. Enterococci must be tested for high-level resistance to streptomycin and gentamicin; if resistance is detected, the addition of an aminoglycoside will not produce a synergistic effect, and the cell wall-active agent should be given alone for periods of 8-12 weeks or-for Enterococcus faecalis-high-dose ampicillin plus ceftriaxone can be given. If treatment fails or the isolate is resistant to commonly used agents, surgical therapy is advised (see below and Table 87-3). The aminoglycoside can be discontinued in those pts who have responded satisfactorily to therapy if toxicity develops after 2-3 weeks of treatment.
• Staphylococcal PVE is treated for 6-8 weeks with a multidrug regimen. Rifampin is important because it kills organisms adherent to foreign material. Two other agents in addition to rifampin help prevent the emergence of rifampin resistance in vivo. Susceptibility testing for gentamicin should be performed before rifampin is given; if the strain is resistant, another aminoglycoside or a fluoroquinolone should be substituted.
• Pts with negative blood cultures and without confounding prior antibiotic treatment should receive ceftriaxone plus gentamicin. If the pt has a prosthetic valve, those two drugs plus vancomycin should be given.

SURGICAL TREATMENT
Surgery should be considered early in the course of illness in pts with the indications listed in Table 87-3, although most of these indications are not absolute. However, pts who develop acute aortic regurgitation with preclosure of the mitral valve or a sinus of Valsalva abscess rupture into the right heart require emergent surgery. Likewise, surgery should not be delayed when severe valvular dysfunction with progressive CHF or uncontrolled or perivalvular infection is present. Cardiac surgery should be delayed for 2-3 weeks if possible when the pt has had a nonhemorrhagic embolic stroke and for 4 weeks when the pt has had a hemorrhagic embolic stroke. Ruptured mycotic aneurysms should be clipped and cerebral edema allowed to resolve prior to cardiac surgery.

ANTIBIOTIC THERAPY AFTER CARDIAC SURGERY

• Uncomplicated NVE caused by susceptible organisms, with negative valve cultures at surgery: The duration of pre- and postoperative treatment should equal the total duration of recommended therapy, with ~2 weeks of treatment given postoperatively.
• Endocarditis with paravalvular abscess, partially treated PVE, or culture-positive valves: Pts should receive a full course of therapy postoperatively.

The American Heart Association has dramatically restricted recommendations for antibiotic prophylaxis, advising prophylaxis only for 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). Table 87-4 lists the high-risk cardiac lesions for which prophylaxis is advised, and Table 87-5 lists the recommended antibiotic regimens for this purpose.

For a more detailed discussion, see Karchmer AW: Infective Endocarditis, Chap. 118, p. 789, in HPIM-17.