Ketoconazole in griseofulvin-resistant dermatophytosis

The efficacy of ketoconazole was evaluated in twenty patients with chronic dermatophyte infections who had failed to clear with griseofulvin therapy. Trichophyton rubrum was the causative organism in nineteen of the patients, and Trichophyton mentagrophytes in one patient. Three of twelve organisms tested showed in vitro resistance to griseofulvin. Duration of infection ranged from 2 to 28 years. Patients received 200 to 400 mg of ketoconazole daily for periods up to 8 months. In addition, patients were followed for 5 months post-therapy to monitor recurrences. Clearing was seen clinically as early as 2 weeks, and by 18 weeks all patients showed marked improvement or clinical clearing, though only six achieved complete mycologic cure. Improvement followed a predictable sequence of sites, with lesions of the trunk healing first, followed by hands, feet, and finally, nails. After 8 months, though all patients showed proximal nail clearing, onychomycosis persisted in thirteen of twenty affected sites. By 5 months post-therapy, four of six patients who had achieved clearing of skin and nails showed recurrences. No significant side effects were observed during therapy, though rare, apparently idiosyncratic cases of hepatotoxicity have been reported. Ketoconazole is an affective therapeutic agent for griseofulvin-resistant dermatophytosis. Apparent cures may subsequently recur after discontinuation of therapy.