The future of antifungal therapy.

Abstract

In the late 1970s the options for systemic antifungal therapy doubled with the addition of intravenous miconazole and oral ketoconazole to the two previously available agents, amphotericin B and flucytosine. The 1980s ushered in the next generation of triazole antifungals, fluconazole and itraconazole. These are the present-day mainstays of treatment for some of the most serious systemic fungal infections. However, the increase in the numbers and types of fungal pathogens, and especially the emergence of azole-resistant fungi, have prompted a continuing search for new therapeutic options. This search has yielded more-potent triazole antifungals, new vehicles for both polyenes and triazoles, and entirely new classes of agents such as the echinocandin derivatives; in addition, it has prompted the evaluation of new combinations of present-day antifungals and exploration of the use of immunomodulators for treatment of fungal infections. Rapid developments in molecular mycology are permitting a concentrated search for more targets for antifungals. We are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases but will have greatly expanded options for treatment.