Asymptomatic blastomycosis of the central nervous system with progression in patients given ketoconazole therapy: a report of two cases.

Ketoconazole (KTZ) has largely replaced amphotericin B as first-line therapy for blastomycosis. However, KTZ penetrates poorly into the central nervous system (CNS), and therapeutic failure may be caused by initially unrecognized CNS infection. Two patients (22% [2/9] of all culture-proven cases of blastomycosis at Grady Memorial Hospital, Atlanta, over 15 years) developed CNS blastomycosis while receiving KTZ. Neither initially had CNS symptoms; both had cutaneous and pulmonary disease that responded to KTZ. If KTZ or other fungistatic imidazoles are to continue as primary therapy for blastomycosis, studies are needed to improve the ability to identify patients likely to experience treatment failure or develop CNS disease. Possibly all patients with disseminated blastomycosis, even those without CNS symptoms, should have lumbar puncture and computed tomography of the head before therapy. Critical evaluation of their immune function also may be required before making a therapeutic decision to use KTZ or amphotericin B.