Table 36–1 summarizes the major properties of currently available antifungal agents. Two different lipid-based amphotericin B formulations are used to treat systemic invasive fungal infections. Their principal advantage appears to be substantially reduced nephrotoxicity, allowing administration of much higher doses. Three agents of the echinocandin class, caspofungin acetate, anidulafungin, and micafungin sodium, are approved for use. The echinocandins have relatively few adverse effects and are useful for the treatment of invasive Candida infections, although resistance is beginning to emerge clinically; C glabrata in particular has shown resistance to this class of antifungals. Caspofungin acetate is also approved for use in refractory cases of invasive aspergillosis. Voriconazole has excellent activity against a broad range of fungal pathogens and has been FDA approved for use in invasive Aspergillus cases, Fusarium and Scedosporium infections, Candida esophagitis, deep Candida infections, and candidemia. Posaconazole has good activity against a broad range of filamentous fungi, including the Mucorales. Some experts recommend therapeutic drug monitoring in individuals with severe invasive fungal infections receiving these newer azoles because of unreliable serum levels due to either metabolic alterations as a result of genetic polymorphisms (voriconazole) or erratic absorption (posaconazole). A delayed-release tablet preparation of posaconazole provides more reliable pharmacokinetics. Isavuconazole has been approved for the treatment of aspergillosis and mucormycosis, although the data for use in the latter are scanty; it is available in an intravenous form that does not utilize the cyclodextrin carrier like previous azoles as well as an oral form with relatively reliable pharmacokinetic properties. As a result of their more frequent and sometimes extended use, newly recognized adverse drug effects are being recognized with the azoles, including peripheral neuropathy (itraconazole and voriconazole) and fluoride excess resulting in periostitis and alkaline phosphatase elevations (voriconazole).
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