Diagnostic methods. Current best practices and guidelines for identification of difficult-to-culture pathogens in...

IE is a serious, life-threatening disease. Because treatment must often be adapted to the pathogen involved, rapid identification of the etiologic agent is critical to successful management of each patient. When difficult-to-culture pathogens are involved, routine microbiologic tests, including blood culture, may remain negative. Because such cases may account for up to 31% of all IE cases, alternative diagnostic approaches are necessary. Among the etiologic agents of culture-negative endocarditis, C burnetii and Bartonella spp play a major role; each is responsible for up to 3% of episodes of IE. The authors therefore recommend the systematic use of specific serologies in all cases of clinically suspected endocarditis. The cross-reactivity between C burnetii, Bartonella spp, and Chlamydia spp is of diagnostic importance because all are potential etiologic agents of endocarditis. However, given that the levels of specific antibodies observed in Bartonella endocarditis are extremely high, low-level cross-reactions with other antigens should not lead to misdiagnosis, provided serology for all suspected agents is performed. When serologic test results are negative for both Bartonella spp and C burnetii, special staining by the Gram, Giemsa, Gimenez, PAS, Warthin-Starry, and Grocott methods may guide the use of new diagnostic tools such as PCR and tissue culture for isolation and identification of the causative agent. Such novel approaches may lead to more comprehensive patient evaluations and the discovery of new etiologic agents of IE.