Systemic fungal infections: diagnosis and treatment. I. Therapeutic agents.

The story of antifungal agents has not been a stately procession from one development to another. For many years there was no agent of value for systemic mycoses. Then, with the advent of amphotericin B, we have had for over two decades essentially one effective agent, but a difficult drug to manipulate. The appearance of ketoconazole, the first systemic drug with relatively little toxicity, along with the appearance of ominous new forms of mycotic diseases, sharply stimulated interest in development of antifungal agents, initially in the azole classes, but now including a variety of other classes as well. We have very little idea how all of these drugs will act independently, and much less how they may interact together. Indeed, one of the most exciting developments is the return to amphotericin B, with repackaging in liposomes having created a markedly less toxic, and possibly much more potent, antifungal agent than "traditional" amphotericin B. There are indeed so many developments under way that the only safe conclusion that can be made is that within a few years current recommendations will be replaced by very different ones for most if not all of the major fungal pathogens.