New Antifungal Agents

For more than two decades, amphotericin B has been the single broad-spectrum agent for the treatment of systemic mycoses. Amphotericin B is not always effective, must be given parenterally, and is associated with a host of adverse reactions. Despite amphotericin B toxicity, until recently the systemic mycoses did not rate enough attention to prompt a search for new alternatives. However, three recent events have overcome this inertia: the gradually increasing use of potent immunosuppressive agents and broad-spectrum antibacterial drugs; the discovery of the relatively nontoxic azole classes of antifungal drugs in the 1980s and the rapid emergence of AIDS, with its severe accompanying opportunistic fungal infections. In just ten years we have seen the emergence of second-generation imidazole and third-generation triazole antifungal drugs and, most recently, entirely new classes of agents. It is remarkable that so many alternatives are becoming available just at the time when new antifungal drugs have become a major need. This discussion will concentrate on the new antifungal drugs of the past ten years, with the exception of developments in the polyenes and flucytosine, which are covered elsewhere.