Update on blood culture-negative endocarditis

Blood culture-negative endocarditis is often severe, and difficult to diagnose. The rate of non-documented infective endocarditis has decreased with the advent of molecular biology - improved performance for the diagnosis of bacterial endocarditis with blood cultures sterilized by previous antibacterial treatment - and cardiac surgery - access to the main infected focus, the endocardium, for half of the patients. Blood culture-negative endocarditis are classified in 3 main categories: (i) bacterial endocarditis with blood cultures sterilized by previous antibacterial treatment (usually due to usual endocarditis-causing bacteria, i.e. streptococci, more rarely staphylococci, or enterococci); (ii) endocarditis related to fastidious microorganisms (e.g. HACEK bacteria; defective streptococci - Gemella, Granulicatella, and Abiotrophia sp. - Propionibacterium acnes, Candida sp.): in these cases, prolonged incubation will allow identifying the causative pathogen in a few days; (iii) and the "true" blood culture-negative endocarditis, due to intra-cellular bacteria that cannot be routinely cultured in blood with currently available techniques: in France, these are most frequently Bartonella sp., Coxiella burnetti (both easily diagnosed by ad hoc serological tests), and Tropheryma whipplei (usually diagnosed by PCR on excised cardiac valve tissue). Non-infective endocarditis is rare, mostly limited to marantic endocarditis, and the rare endocarditis related to systemic diseases (lupus, Behçet).