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INTRODUCTION

Compared with antibacterial agents, relatively few antimicrobials are available for treatment of fungal infections. Many substances with antifungal activity have proven to be unstable, to be toxic to humans, or to have undesirable pharmacologic characteristics, such as poor diffusion into tissues. Newer antifungal agents target fungal-specific cellular features and demonstrate lower toxicity than older drug classes.

Many antifungals are too toxic for use

Many fungal infections are self-limiting and require no therapy. However, there are also circumstances in which either topical or systemic antifungal agents are used. Superficial mycoses are often treated with topical therapy, limiting toxicity to the host. Invasive or systemic fungal infections that are not controlled by the host’s immune system often require the prolonged use of systemic antifungals. Given that most of the patients with these infections also have underlying immunosuppression, invasive mycosis can be among the most difficult of all infectious diseases to treat successfully. The characteristics of currently used antifungal agents are summarized in Table 44–1. They are also discussed in the text that follows in relation to their target of action, as illustrated in Figure 44–1.

FIGURE 44–1.

Sites of action of antifungal agents. This figure demonstrates the cellular targets of the major antifungal agents: (1) cell wall (echinocandins and nikkomycin—an experimental chitin synthase inhibitor), (2) cell membrane (azoles, amphotericin B), and (3) nucleic acid synthesis (flucytosine).

TABLE 44–1Features of Antifungal Agents

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