Fungal infections and their management.

The first oral agents for treatment of mycoses included potassium iodide, griseofulvin and flucytosine. While each is still used in specific indications, the advent of ketoconazole in the late 1980s radically expanded the spectrum and efficacy of oral antifungals. Ketoconazole was the first drug sufficiently potent and benign to permit use for both superficial and deep fungal infections. Ketoconazole quickly proved highly effective in many systemic and cutaneous infections, but it was soon appreciated that high doses caused impairment of testosterone and ultimately cortisol synthesis. Dose-dependent nausea and vomiting also became apparent, as did the necessity for very high doses for treatment of fungal meningitis. Hepatic cellular toxicity was also noticed, particularly after prolonged treatment at high doses. Just as these limitations became apparent, Janssen, Pfizer and, most recently, Schering brought forth the triazole antifungals. These differ markedly in pharmacokinetics and fungal spectrum, requiring careful consideration of the appropriate drug. In addition to the above, terbinafine has been recently developed for dermatophytes, particularly refractory onychomycoses.