Ketoconazole therapy for endemic blastomycosis.

Amphotericin B is effective in therapy for blastomycosis but causes a number of serious adverse reactions. Because ketoconazole has in-vitro activity against Blastomyces dermatitidis, we administered this agent in a dosage of 400 mg/d to 46 patients with blastomycosis, with 43 patients receiving at least 1 month of therapy. Thirty-five patients had cure without relapse over a mean follow-up of 17 months. Six had a relapse of infection but 4 of these had been noncompliant with therapy. Two patients improved initially but ultimately had progression of disease despite maintenance of adequate serum levels. Adverse effects were common but not severe. Three patients with extensive infection died--2 had received only one dose of ketoconazole and 1 had received therapy for only 2 weeks. The cure rate in these patients suggests that ketoconazole may replace amphotericin B as the initial treatment of blastomycosis that is not overwhelming.