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Diagnostic strategy for blood culture-negative endocarditis.

result of empirical antibiotic treatment before blood culture sampling. 2. Zoonotic agents, especially Coxiella and Bartonella species, are important causes of BCNE and may be prevalent. In the first case, streptococci, being the most common and antibiotic-susceptible agents of infective endocarditis overall, are cleared from the bloodstream, and valve tissue, from patients undergoing surgery, may be used for diagnosis through histopathological analysis and molecular biology tools. Considering all etiologies, the molecular biology tools used provided a diagnosis for 14% of blood samples and two-thirds of the valves studied, through broad-range polymerase chain reaction (PCR) (16S ribosomal DNA and 18S ribosomal DNA PCR assays). Concerning the zoonotic agents Bartonella and Coxiella species, results of serological analysis were positive, with titers compatible with endocarditis in nearly half the patients (47.7%) in the series. Because treatment for Bartonella endocarditis should include an aminoglycoside, since this affects the outcome, and because treatment for Coxiella endocarditis is long and specific (doxycycline plus cloroquine for many months, with close serological follow-up to determine cure), it is mandatory to rule in or rule out these diagnoses as early as possible in the workup. This study also brings new messages to the field: sophisticated methods, such as primer extension enrichment reaction (PEER) identified very few additional cases, and this was also the case for autoimmunohistochemistry of valvular tissue. Also, cell culture did not provide any additional diagnoses beyond those determined by serological analysis and PCR. Therefore, these tests should be used in exceptional circumstances. Histopathological analysis remains very important, and several diagnoses that were not infective were made on the basis of such analysis, including angiosarcoma and myxoma, as well as Libman-Sachs endocarditis, marantic endocarditis, and Behcet-associated endocarditis.