New Classes of Antifungal Drugs

The echinocandins and their analogs, the pneumocandins, represent the newest class of antifungal drugs (19,29,31–40). They inhibit the synthesis of 1,3-b-D-glucan, a fundamental component of the fungal cell wall by the inhibition of 1,3 b-D-glucan synthase, an enzyme complex that forms glucan polymers in the cell wall and is absent in mammalian cells. The inhibition is effective and specific, and brief exposure leads to cell death. The potent antifungal activity of the echinocandins against Candida species was demonstrated by Cuenca-Estrella et al. (33) and Quindos et al. (24), who evaluated the in vitro activity of LY303366, a semi-synthetic echinocandin B derivative, against 156 clinical isolates of Candida species and 36 C. dubliniensis clinical isolates, respectively. Results showed that LY303366 had potent activity against several Candida species including C. albicans, C. tropicalis, as well as C. glabrata and C. krusei, two species usually considered refractory to azoles. Similarly, 100% of the isolates were susceptible to the new antifungal drugs, indicating that echinocandins may provide new alternatives to fluconazole for treating C. dubliniensis infections (24). The excellent in vitro activity of echinocandins demonstrated against fluconazole-resistant Candida species strains indicates that the echinocandins are very promising as novel antifungal agents with important implications for the treatment of infections by these yeasts (24,33,34). Their unique mode of action and their specificity to fungal cell walls result in minimal toxicity to mammalian cells.