Abstract
BACKGROUND: Prosthetic valve endocarditis due to Histoplasma capsulatum is exceedingly rare and difficult to diagnose. CASE SUMMARY: A 79-year-old man with a bioprosthetic mitral valve presented with subacute cognitive decline, pancytopenia, and hypercalcemia. He was afebrile and hemodynamically stable. Echocardiography showed vegetations on the valve. Initially, blood cultures were negative. Urine Histoplasma antigen and serum beta-D-glucan were positive, and fungal blood cultures later grew H capsulatum after 4 weeks of incubation. He was managed with liposomal amphotericin B followed by isavuconazole due to itraconazole contraindications. He gradually recovered without surgical intervention. DISCUSSION: This case illustrates the diagnostic and treatment complexities of Histoplasma endocarditis. TAKE-HOME MESSAGES: In endemic regions, consider Histoplasma in culture-negative prosthetic valve endocarditis. Early diagnosis may rely on beta-D-glucan and H capsulatum urine antigen before cultures become positive. Isavuconazole is a viable alternative when itraconazole is not an option. Selected patients can be managed successfully without surgery.