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Epidemiology, microbiology, and diagnosis of culture-negative endocarditis

Didier Raoult, MD, PhD
Daniel J Sexton, MD
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Infective endocarditis (IE) remains a diagnostic challenge in some patients. Identification of the etiologic agent is critical to selecting an appropriate treatment, as the fatality rate remains high [1]. The proportion of IE that is without an etiologic diagnosis varies from country to country and among different centers in the same country. These variations reflect the local epidemiology of IE, diagnostic criteria used, initiation of antibiotics in patients prior to obtaining blood cultures, and the diagnostic protocol used to establish an etiology [2].

The epidemiology and microbiology of culture-negative endocarditis will be reviewed here. Criteria for the diagnosis of IE and treatment are discussed separately. (See "Clinical manifestations and evaluation of adults with suspected native valve endocarditis" and "Antimicrobial therapy of native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis".)


The epidemiology of blood culture-negative infective endocarditis (IE) varies by country and host, as exposure to infection with highly fastidious bacteria (many zoonotic) or fungi depends on whether the organism is endemic to the area and whether the host is particularly susceptible to infection with the organism.

Definition — Blood culture-negative IE is defined as endocarditis without etiology following inoculation of at least three independent blood samples in a standard blood-culture system with negative cultures after five days of incubation and subculturing [2].

Incidence — Cultures remain negative in 2 to 7 percent of patients with IE even when the utmost care is taken in obtaining the proper number and volume of blood cultures and patients with prior antibiotic treatment are excluded; the frequency is higher in patients who have already been treated with antibiotics [3-7].

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Literature review current through: Nov 2017. | This topic last updated: Oct 28, 2016.
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