Systemic antifungal agents. What is in the pipeline?

With the increase in serious and often life-threatening fungal infections over the last 2 decades, there has been an enhanced effort to bring new antifungal agents into the therapeutic armamentarium. The introduction of new agents into the clinical setting has been slow, in part because several drugs which appeared promising in vitro and in short term animal studies later proved to be toxic. Toxicity has been a major hurdle in the development of antifungal agents because mammalian cells, in contrast to bacterial cells, share with fungal cells many structures and metabolic pathways. For example, the 2 most common classes of antifungal agents, polyenes and azoles, target the synthesis of the cell membrane, a structure shared by both mammalian and fungal cells, and thus these drugs have inherent toxicity. Antifungal agents that act on protein synthesis are also inherently toxic to mammalian as well as fungal cells. New agents that target the fungal cell wall, a structure with no homology in mammalian cells, may prove to be less toxic and are currently of great interest.