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In order to avoid delayed or missed diagnosis, careful clinical, microbiologic, and echocardiographic evaluation should be pursued when febrile patients have endocarditis predispositions, cardiac or noncardiac features of endocarditis, or microbiologic findings consistent with endocarditis (e.g., a stroke or splenic infarct, multiple positive blood cultures for an endocarditis-associated organism).

The Duke Criteria

The diagnosis of infective endocarditis is established with certainty only when vegetations are examined histologically and microbiologically. Nevertheless, a highly sensitive and specific diagnostic schema—known as the modified Duke criteria—is based on clinical, laboratory, and echocardiographic findings commonly encountered in patients with endocarditis (Table 155-3). While developed as a research tool rather than for patient management, the criteria can be a helpful diagnostic tool. If the criteria are to be maximally helpful in evaluating patients, appropriate data must be collected. Furthermore, clinical judgment must be exercised in order to use the criteria effectively. Documentation of two major criteria, of one major criterion and three minor criteria, or of five minor criteria allows a clinical diagnosis of definite endocarditis. The diagnosis of endocarditis is rejected if an alternative diagnosis is established, if symptoms resolve and do not recur with ≤4 days of antibiotic therapy, or if surgery or autopsy after ≤4 days of antimicrobial therapy yields no histologic evidence of endocarditis. Illnesses not classified as definite endocarditis or rejected as such are considered cases of possible infective endocarditis when either one major and one minor criterion or three minor criteria are fulfilled. Requiring some clinical features of endocarditis for classification as possible infective endocarditis increases the specificity of the schema without significantly reducing its sensitivity. Unless there are extenuating circumstances, patients with definite or possible endocarditis are treated as such.

TABLE 155-3The Modified Duke Criteria for the Clinical Diagnosis of Infective Endocarditisa

The criteria emphasize bacteremia and echocardiographic findings typical of endocarditis. The requirement for multiple positive blood cultures over time is consistent with the continuous low-density bacteremia characteristic of endocarditis. Among patients with untreated endocarditis who ultimately have a positive blood culture, 95% of all blood cultures are positive. The diagnostic criteria attach significance to the species of organism isolated from blood cultures. To fulfill a major criterion, the isolation of an organism that causes both endocarditis and bacteremia in the absence of endocarditis (e.g., S. aureus, enterococci) must take place repeatedly (i.e., persistent bacteremia) and in the absence of a primary focus of infection. Organisms that rarely cause endocarditis but commonly contaminate blood cultures (e.g., diphtheroids, CoNS) must be isolated repeatedly if their isolation is to serve as a major criterion.

Blood Cultures

Isolation of the causative microorganism from blood cultures is critical for diagnosis and for planning treatment. In patients with suspected NVE, PVE, or CIED endocarditis who have not received antibiotics during the prior 2 weeks, three 2-bottle blood culture sets, separated from one another by at least 2 h, should be obtained from different venipuncture sites over 24 h. If the cultures remain negative after 48–72 h, two or three additional blood culture sets should be obtained, and the laboratory should be consulted for advice regarding optimal culture techniques. Pending culture results, empirical antimicrobial therapy should be withheld initially from hemodynamically stable patients with suspected subacute endocarditis, especially those who have received antibiotics within the preceding 2 weeks. Thus, if necessary, additional blood culture sets can be obtained without the confounding effect of empirical treatment. Patients with acute endocarditis or with deteriorating hemodynamics who may require urgent surgery should receive empirical treatment immediately after three sets of blood cultures are obtained over several hours.

Non-Blood-Culture Tests

Serologic tests can be used to implicate organisms that are difficult to recover by blood culture: Brucella, Bartonella, Legionella, Chlamydia psittaci, and C. burnetii. Pathogens can also be identified in vegetations by culture, microscopic examination with special stains (i.e., the periodic acid–Schiff stain for T. whipplei), or direct fluorescence antibody techniques and by the use of polymerase chain reaction to recover unique microbial DNA or DNA encoding the 16S or 28S ribosomal unit (16S rRNA or 28S rRNA); sequencing of these DNAs allows identification of bacteria and fungi, respectively.


Echocardiography anatomically confirms and measures vegetations, detects intracardiac complications, and assesses cardiac function (Fig. 155-3). Transthoracic echocardiography (TTE) is noninvasive and exceptionally specific; however, it cannot image vegetations <2 mm in diameter, and in 20% of patients it is technically inadequate because of emphysema or body habitus. TTE detects vegetations in 65–80% of patients with definite clinical endocarditis but is not optimal for evaluating prosthetic valves or detecting intracardiac complications. TEE is safe and detects vegetations in >90% of patients with definite endocarditis; nevertheless, initial studies may yield false-negative results in 6–18% of endocarditis patients. When endocarditis is likely, a negative TEE result does not exclude the diagnosis but rather warrants repetition of the study once or twice in 7–10 days. TEE is the optimal method for the diagnosis of PVE, the detection of myocardial abscess, valve perforation, or intracardiac fistulae and for the detection of vegetations in patients with CIED. In patients with CIED and negative blood cultures, a mass adherent to the lead is likely to be a bland thrombosis rather than an infected vegetation.

FIGURE 155-3

Imaging of a mitral valve infected with Staphylococcus aureus by low-esophageal, four-chamber-view, transesophageal echocardiography (TEE). A. Two-dimensional echocardiogram showing a large vegetation with an adjacent echolucent abscess cavity. B. Color-flow Doppler image showing severe mitral regurgitation through both the abscess-fistula and the central valve orifice. A, abscess; A-F, abscess-fistula; L, valve leaflets; LA, left atrium; LV, left ventricle; MR, mitral central valve regurgitation; RV, right ventricle; veg, vegetation. (With permission of Andrew Burger, MD.)

Because S. aureus bacteremia is associated with a high prevalence of endocarditis, routine echocardiographic evaluation (TTE or preferably TEE) is recommended in these patients. Patients with nosocomial S. aureus bacteremia are at increased risk of endocarditis if one or more of the following are present: positive blood cultures for 2–4 days, hemodialysis dependency, a permanent intracardiac device, spine infection, nonvertebral osteomyelitis, or an endocarditis-predisposing valve abnormality. Ideally, these patients should be evaluated with TEE. In patients with none of these findings, the risk of endocarditis is low and evaluation with TTE may suffice.

Experts favor echocardiographic evaluation of all patients with a clinical diagnosis of endocarditis; however, the test should not be used to screen patients with a low probability of endocarditis (e.g., patients with unexplained fever). An American Heart Association approach to the use of echocardiography for evaluation of patients with suspected endocarditis is illustrated in (Fig. 155-4).

FIGURE 155-4

The diagnostic use of transesophageal and transtracheal echocardiography (TEE and TTE, respectively). High initial patient risk for infective endocarditis (IE), as listed in Table 155-8, or evidence of intracardiac complications (new regurgitant murmur, new electrocardiographic conduction changes, or congestive heart failure). *High-risk echocardiographic features include large vegetations, valve insufficiency, paravalvular infection, or ventricular dysfunction. Rx indicates initiation of antibiotic therapy. (Reproduced with permission from Diagnosis and Management of Infective Endocarditis and Its Complications. Circulation 98:2936, 1998. © 1998 American Heart Association.)

Other Studies

Many studies that are not diagnostic—i.e., complete blood count, creatinine determination, liver function tests, chest radiography, and electrocardiography—are important in the management of patients with endocarditis. The erythrocyte sedimentation rate, C-reactive protein level, and circulating immune complex titer are commonly increased in endocarditis (Table 155-2). Cardiac catheterization is useful primarily to assess coronary artery patency in older individuals who are to undergo surgery for endocarditis.

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