Current and Future Antifungal Agents

JOHN H. REX, MD.

Abstract: 

Amphotericin B (AmB) is the broadest spectrum and most generally reliable agent. It is preferred when the infecting isolate is not certain or (asp. with Candida) when prior azole use may have selected azole resistance. Lipid AmB preparations reduce but do not eliminate AmB's toxicity. The lipids alter Atoll's pharmacology & the full consequences of this are unknown. 2-3 mg/kg/day appears suitable for candidiasis, whereas 5 mg/kg/d (possibly more) is needed for invasive moulds. Liposomal nystatin may be active against some AMB-resistant fungi, and a lipid preparation may permit systemic use. Fluconazole is active in candidiasis, cryptococcosis, and coccidioidomycosis. Its low toxicity has led to interest in extending its utility by using higher doses. Itraconazole has broad activity. The oral solution enhances bioavailability. A new IV form achieves adequate blood levels rapidly, with less patient-to-patient variability than the oral forms. Lack of data on the IV form's cyclodextrin carrier limits use to patients with CrCl ? 30 ml/min. New azole agents. In preclinical studies, posaconazole, ravuconazole, and voriconazole have activity that extends beyond prior drugs for selected fungi. They are now undergoing trials in man. Flucytosine's potential for toxicity and development of resistance during monotherapy limit its use. Echinocandins. FK463, caspofungin, and VER002 are glucan synthase inhibitors. They are fungicidal for all Candida app. and also inhibit Aspergillus but not Cryptococcus or (by in vitro data) most non-Aspergillus moulds. Their low toxicity in studies to date makes them attractive, especially for serious candidiasis. Terbinafine, like the azoles, inhibits ergosterol synthesis but by inhibiting squalene epoxidase rather than 14-ademethylase. Alone it has excellent activity in onychomycosis & it also has intriguing activity in combination with other antifimgals against more invasive pathogens.
2000

abstract No: 

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Full conference title: 

IDSA 38th
    • IDSA 38th