The prevalence of infective endocarditis with negative blood cultures varies in the different series from 5 to 25%. There are certain explanations of negative blood culture endocarditis: previous incorrect antibiotic therapy before obtaining blood samples (antibiotic treatment inhibits the growth of germs, and therefore bacteremia, without sterilizing the vegetations); infective endocarditis due to fastidious microorganism, that is of difficult cultivation and identification; infective endocarditis due to cell-dependent organism (e.g. Coxiella burnetii); infective endocarditis due to fungi; non-infectious involvement of the endocardium (at times with vegetations) during the course of certain disease. We underline three etiologies (Coxiella burnetii, Bartonella species and Whipple's disease bacterium) because their study have constituted the stimulus for the introduction into clinical evaluation of patients with suspected infective endocarditis of different diagnostic approaches, based on a correct sequential application of blood cultures, serodiagnosis and molecular microbiology.

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