Ketoconazole in the Treatment of Coccidioidomycosis

Ketoconazole is the newest antifungal agent evaluated for efficacy in the treatment of coccidioidomycosis and the only one used by oral administration. The inhibition of Coccidioides immitis observed by in vitro susceptibility testing has been corroborated in murine studies in which ketoconazole therapy has led to survival in otherwise lethally infected animals. In man, absorption of ketoconazole from the gastrointestinal tract is generally favourable. However, there is considerable variation between patients in achieved serum concentrations, the causes of which may be multiple and as yet are incompletely understood. All completed studies of ketoconazole treatment of human coccidioidomycosis have been non-comparative in design. Entry criteria have selected patients that would have been treated otherwise with another antifungal agent. Dosages were usually 200 or 400 mg/day and treatment was continued for many months. Soft tissue infections improved more frequently and after less ketoconazole than did pulmonary or skeletal infections. No effect on coccidioidal meningitis has been found at these dosages. In skeletal infections, symptoms, physical findings and coccidioidal antibody levels commonly improved, but radiographs of skeletal lesions frequently did not change. Repeat culture of treated lesions, even those that had improved, often continued to grow C. immitis. Relapses after stopping ketoconazole have occurred in a significant number of patients. Untoward effects were usually manageable without discontinuing therapy. Ketoconazole appears to be of use in the treatment of progressive forms of coccidioidomycosis. However, the optimum dose and duration of ketoconazole therapy have not yet been defined. Furthermore, its efficacy relative to other antifungals has not been studied.