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INTRODUCTION

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There are 200,000 known species of fungi, and estimates of the total size of Kingdom Fungi range to well over a million. Residents of the kingdom are quite diverse and include yeasts, molds, mushrooms, smuts, the pathogens Aspergillus fumigatus and Candida albicans, and the source of penicillin, Penicillium chrysogenum. Fortunately, only ~400 fungi cause disease in animals, and even fewer cause significant human disease. However, fungal infections are becoming more common in patients with compromised immune systems. Fungi are eukaryotes with unique cell walls containing glucans and chitin, and their eradication requires different strategies than those for treatment of bacterial infections. Available agents have effects on the synthesis of membrane and cell-wall components, on membrane permeability, on the synthesis of nucleic acids, and on microtubule/mitotic spindle function (Figure 57-1). Antifungal agents described in this chapter are discussed under two major headings, systemic and topical, although this distinction is somewhat arbitrary. The imidazole, triazole, and polyene antifungal agents may be used either systemically or topically, and many superficial mycoses can be treated either systemically or topically. Table 57-1 summarizes common mycoses and their pharmacotherapy.

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Table 57–1Pharmacotherapy of Mycoses
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figure 57–1

Sites of action of antifungal drugs. Amphotericin B and other polyenes (e.g., nystatin) bind to ergosterol in fungal cell membranes and increase membrane permeability. The imidazoles and triazoles (itraconazole, et al.) inhibit 14-α-sterol demethylase, prevent ergosterol synthesis, and lead to the accumulation of 14-α-methylsterols. The allylamines (e.g., naftifine and terbinafine) inhibit squalene epoxidase and prevent ergosterol synthesis. The echinocandins, such as caspofungin, inhibit the formation of glucans in the fungal cell wall.

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SYSTEMIC ANTIFUNGAL AGENTS

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DRUGS FOR DEEPLY INVASIVE FUNGAL INFECTIONS

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AMPHOTERICIN B. Amphotericin ...

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