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High-Dose Ketoconazole for Treatment of Fungal Infections of the Central Nervous System

PHILIP C. CRAVEN, M.D.; JOHN R. GRAYBILL, M.D.; JAMES H. JORGENSEN, Ph.D.; WILLIAM E. DISMUKES, M.D.; and BERNARD E. LEVINE, M.D.
[+] Article and Author Information

This work was supported by the General Medical Research Service and the Special Diagnostic and Treatment Unit of the Veterans Administration.

▸Requests for reprints should be addressed to Philip C. Craven, M.D. (111F); Audie L. Murphy Memorial Veterans Administration Hospital, 7400 Merton Minter Blvd.; San Antonio, TX 78284.


San Antonio, Texas; Birmingham, Alabama; and Phoenix, Arizona


© 1983 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1983;98(2):160-167. doi:10.7326/0003-4819-98-2-160
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Mortality and complication rates remain unacceptably high with conventional intravenous and intrathecal therapy for patients with coccidioidal meningitis and intracerebral fungal lesions. We studied the ventricular and lumbar cerebrospinal fluid penetration of ketoconazole and the responses to therapy in two patients receiving ketoconazole orally, 800 mg daily, and amphotericin B intraventricularly for meningeal and extrameningeal coccidioidomycosis. Five patients received only 1200 mg of ketoconazole: one had uncomplicated coccidioidal meningitis, three had obstructive hydrocephalus due to coccidioidal meningitis, and one had a histoplasmal brain abscess. Ketoconazole concentrations in ventricular and lumbar fluid ranged from 0.05 to 1.65 µg/mL 4 and 8 hours after the dose. The mean penetration of ketoconazole (± SD) was 1.9% ± 0.8% for ventricular fluid and 5.4% ± 2.6% for lumbar fluid. Ketoconazole concentrations in cerebrospinal fluid varied directly with those in serum and with cerebrospinal fluid protein content. The encouraging clinical responses, convenience, safety, and the consistent penetration of ketoconazole into obstructed and nonobstructed cerebrospinal fluid support the use of these regimens as alternatives to conventional therapy.

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