ABSTRACT

The most widely exploited strategy for antifungal therapy makes use of differences in sterol biosynthesis and targets either the ergosterol biosynthesis pathway or ergosterol itself, which is incorporated into the fungal cell membrane. Fluconazole is available in both an oral and intravenous formulations and has been widely studied in treating invasive fungal disease. Current approved agents by the Food and Drug Administration are caspofungin, micafungin and anidulafungin. G. Chamilos et al. showed that paradoxical growth was more frequent in caspofungin than with micafungin and anidulafungin and was completely absent in C. glabrata isolates. Overexpression of efflux pumps is a common mechanism of resistance to drugs toxic to the fungal cell. The established mechanisms of resistance are all able to individually contribute to azole resistance but high-level resistance is mainly due to multiple mechanisms of resistance that accumulate over time. Amphotericin B's primary fungicidal mechanism of action is the direct binding to ergosterol; the primary sterol found in fungal cell membranes.