The great majority of patients with endocarditis have positive blood cultures within a few days of incubation and only a few cases will become positive on further incubation for 1–2 weeks. The proportion of culture-negative cases depends on the volume of blood and method of culture but a common estimate is 5% with a range from 2.5% to 31%.1 Most cases of culture-negative endocarditis are related to use of antibiotics within the preceding two weeks and probably represent infections with staphylococci, streptococci or enterococci. If antibiotics have been given, withdrawal of treatment for four days and serial blood cultures will usually demonstrate the pathogen.

A number of organisms may grow only if incubated under the correct conditions. Nutritionally-deficient streptococci may fail to grow in ordinary media and yet are part of the normal mouth flora and can cause endocarditis.2 The HACEK organisms are slow
growing and easily missed. Coxiella burnetti, Chlamydia spp. and Mycoplasma spp. are rare causes of endocarditis and are difficult to grow, diagnosis requiring biopsy or serology. Bartonella spp. are now known to cause endocarditis in homeless patients and diagnosis
is difficult by conventional methods.

Three sets of blood cultures will demonstrate at least 95% of culturable organisms causing endocarditis. After four negative cultures there is only a 1% chance of an organism being identified by later culture.4 Contamination as the result of poor collection technique makes interpretation difficult and is a greater risk when repeated sets of culture are collected.

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