Treatment of Coccidioidomycosis with Ketoconazole: Clinical and Laboratory Studies of 18 Patients

Abstract

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 ∼2 µg/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.