Ketoconazole was given to 18 patients with
coccidioidomycosis. Fourteen had received prior antifungal
chemotherapy with
amphotericin B,
miconazole, or both. Ten patients had
pulmonary disease, two had
meningitis, and six had extrameningeal disseminated disease. The initial dose of
ketoconazole was 200 mg per day; it was later increased to 400 mg per day for some patients. All strains of Coccididioides immitis tested were sensitive to
ketoconazole. Approximately 2-4 hr after an oral dose of 200 mg of
ketoconazole, levels of the
drug in blood peaked at approximately 2 micrograms/ml. Higher concentrations in blood were achieved with a 400-mg dose. Improvement was measured by physical examination, conversion of cultures previously positive for C. immitis to negative, decrease in erythrocyte sedimentation rate by 50%, and decrease in titer of
complement fixation antibody by two or more dilutions. One patient died after one week of treatment with
ketoconazole and could not be evaluated; two other patients with coccidioidal
meningitis could not be evaluated. Six of nine patients with
pulmonary disease showed radiographic improvement, and their sputum cultures, which had been positive, became negative. Four of the six patients with disseminated disease improved. There were few adverse reactions to
ketoconazole, which can be safely administered for prolonged periods to patients with
coccidioidomycosis. These findings suggest that
ketoconazole may be effective for treatment of this disease and indicate that trials comparing the efficacy of
ketoconazole with that of
amphotericin B are warranted.