Risk factors prior IE, presence of a prosthetic valve or cardiac device, or history of valvular or congenital heart disease) and noncardiac factors (intravenous drug use, indwelling intravenous catheter, immunosuppression, or a recent dental or surgical procedure). (

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●IE is associated with a broad array of systemic complications; these include cardiac and neurologic complications, septic emboli, metastatic infection, and systemic immune reactions. Clinical manifestations reflecting these complications may be present at the time of initial presentation and/or may develop subsequently. Clinical manifestations of a complication of IE warrant independent diagnostic evaluation, concurrent with evaluation for IE. (See 'Complications as presenting symptoms' above.)

●The diagnosis of IE should be suspected in patients with fever (with or without bacteremia) in the setting of relevant cardiac and noncardiac risk factors. The diagnosis is established based on clinical manifestations, blood cultures (or other microbiologic data), and echocardiography. The accepted criteria for diagnosis of IE are the modified Duke criteria, which are summarized above and in the tables (table 1 and table 2) (calculator 1). (See 'Overview of diagnostic approach' above and 'Modified Duke criteria' above.)

●At least three sets of blood cultures should be obtained from separate venipuncture sites prior to initiation of antibiotic therapy. For patients who are clinically stable, antimicrobial therapy may be deferred while awaiting the results of blood cultures and other diagnostic tests. For patients with signs of clinical instability, initiation of empiric antimicrobial therapy (after three blood cultures have been obtained) is appropriate. (See 'Overview of diagnostic approach' above.)

●Typical microorganisms consistent with IE include Staphylococcus aureus, viridans streptococci, Streptococcus gallolyticus (formerly S. bovis), HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) organisms, or community-acquired enterococci. (See 'Modified Duke criteria' above.)

●Culture-negative IE should be suspected in patients with negative blood cultures and persistent fever with one or more clinical findings consistent with infective endocarditis (eg, stroke or other manifestations of emboli). Culture-negative IE should also be suspected in patients with vegetation on echocardiogram and no clear microbiologic diagnosis. (See 'Culture-negative endocarditis' above and "Culture-negative endocarditis: Epidemiology, microbiology, and diagnosis".)

●Echocardiography should be performed in patients with suspected IE (table 1 and table 2 and algorithm 1). In general, transthoracic echocardiography (TTE) is the first diagnostic test for patients with suspected IE. Transesophageal echocardiography (TEE) has higher sensitivity than TTE and is better for detection of cardiac complications such as abscess, leaflet perforation, and pseudoaneurysm. In some circumstances, it is reasonable to forgo TTE and proceed to TEE. (See 'Echocardiography' above.)

●Additional evaluation for patients with suspected IE includes electrocardiography, chest radiography, other radiographic imaging tailored to clinical manifestations, and dental evaluation. (See 'Overview of diagnostic approach' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Vance G Fowler, Jr, MD, who contributed to an earlier version of this topic review.