Therapy for opportunistic fungal infections: past, present and future

Abstract

The field of antifungal chemotherapy is presently rapidly moving. It began in 1903, with the successful use of potassium iodide (KI). Then there was little progress for 50 years, when in 1951, nystatin was introduced, the first useful polyene. Four years later amphotericin B followed, which is still the historical standard against which new systemic antifungals are compared. Except for the development of flucytosine, there was little progress until the early 1970s and the development of the azole drugs. The present era, which is characterized largely by the modifications of azole drugs, began with ketoconazole and brought agents which can be given orally and have increasing potency, decreasing toxicity and a broader spectrum of activity. Recent studies have examined ways to ameliorate the well-known toxicities of amphotericin B. A new approach has been to complex the drug with lipids or entrap it in liposomes. Itraconazole is a broad-spectrum oral triazole whose greatest advantages over the imidazoles are in its activity against aspergillosis and cryptococcosis, though it is also efficacious against the endemic deep mycoses. Fluconazole is a broad-spectrum triazole. It has been shown to be efficacious in various forms of superficial candidosis, including esophageal disease. We have shown in a randomized, double-blind, placebo-controlled study that maintenance therapy can completely prevent thrush in AIDS patients with recurrent thrush and possibly prevent all deep and superficial mycoses. Other studies have shown efficacy in cryptococcal meningitis in AIDS comparable to conventional therapy and with far less toxicity, and also in prevention of relapse of cryptococcal disease. Early diagnosis of fungal infections in cancer patients is problematic.(ABSTRACT TRUNCATED AT 250 WORDS)