Blood culture-negative infective endocarditis: Organisms, risk factors, and diagnostic tests

	Risk factors	Diagnostic tests^*
Fastidious organisms
Fungi
Candida	Nosocomial exposure Prosthetic valve placement Injection drug use	Blood culture Tissue stain: Gomori-Grocott
Aspergillus	Nosocomial exposure Prosthetic valve placement Immunosuppression	Blood culture Tissue stain: Gomori-Grocott
Histoplasma	Geographical exposure^¶	Histoplasma serum and/or urine antigen Tissue stain: Gomori-Grocott
Coccidioides	Geographical exposure^Δ	Coccidioides serology and antigen Tissue stain: Gomori-Grocott
Atypical mycobacteria
M. chimaera (slow grower)	Cardiac surgery	AFB culture (blood or tissue)
Rapid growers: M. abscessus M. chelonae M. fortuitum	Recent prosthetic valve placement	AFB culture (blood or tissue)
Mycoplasma spp M. hominis M. pneumoniae	Cardiac surgery, especially prosthetic valve placement	Mycoplasma culture (M. hominis) Tissue stain: Ziehl-Neelsen or Kinyoun
Brucella spp	Exposure to cattle, sheep, goats, unpasteurized milk	Blood culture Brucella serology
Legionella spp	Prior history of Legionella pneumonia Immunosuppression Prosthetic valve placement	Blood or tissue culture on special media Urine Legionella antigen Tissue stain: Gimenez
Intracellular bacteria
*Coxiella burnetii*	Exposure to cattle, sheep, goats, cats Prosthetic valve placement Pre-existing valvulopathy	Coxiella serology Coxiella PCR (plasma or serum) Tissue stain: Gimenez
Bartonella spp
B. quintana	Undomiciled status Heavy alcohol use	Bartonella serology Bartonella PCR (plasma or serum) Tissue stain: Warthin-Starry
B. henselae	Cat exposure	Bartonella serology Bartonella PCR (plasma or serum) Tissue stain: Warthin-Starry
*Tropheryma whipplei*	Immunosuppression Pre-existing valvulopathy	T. whipplei plasma/serum PCR Tissue stain: periodic acid-Schiff
Legionella spp	Prior history of Legionella pneumonia Immunosuppression Prosthetic valve placement	Blood or tissue culture on special media Urine Legionella antigen Tissue stain: Gimenez
*Chlamydia psittaci*	Bird exposure	C. psittaci serology Tissue stain: Macchiavello

AFB: acid-fast bacillus; PCR: polymerase chain reaction.

* PCR of valve tissue recommended in all cases of blood culture-negative endocarditis in which a pathogen has not been identified by the time of surgery.

¶ Endemic areas for histoplasmosis include the Mississippi and Ohio river valleys, the Caribbean, southern Mexico, certain parts of Central and South America, Africa, and Asia. Refer to UpToDate content on histoplasmosis for further discussion.

Δ Endemic areas for coccidioidomycosis include specific areas of California, Arizona, Nevada, Utah, and New Mexico, as well as northern Mexico and areas of Central and South America. Refer to UpToDate content on coccidioidomycosis for further discussion.

Graphic 144430 Version 2.0

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Blood culture-negative infective endocarditis: Organisms, risk factors, and diagnostic tests