Chapter 29

In the most general scientific sense, a “parasite” includes all of the known infectious agents such as viruses, bacteria, fungi, protozoa (single-celled eukaryotes of the animal kingdom), and helminths (worms) that live in or on host tissue, generally at the expense of the host. Certain species of parasites cause human infections. Some infections, especially fungal, are common in both industrialized and underdeveloped nations and cause varying degrees of illness and debility. Diseases caused by protozoan and helminthic parasites are among the leading causes of disease and death in tropical and subtropical regions. Many of these infections are intensified by inadequate water sanitation and hygiene, and their management is hampered by difficulty in controlling the vector (e.g., mosquito, in the case of malaria). This chapter describes the most commonly used drugs to treat fungal, protozoan, and helminthic infections.

Most human mycoses—diseases caused by fungal infections—are minor or superficial. However, the incidence and severity of human fungal infections have increased dramatically over the last few decades. This shift reflects the enormous number of immunocompromised patients (secondary to HIV and immunosuppressive drugs) who are at increased risk for invasive fungal infections, as well as the widespread use of broad-spectrum antimicrobials, which eliminate competitive nonpathogenic bacteria. In addition, fungi (especially Candida species) may be introduced into tissues that are normally resistant to invasion by, for example, central intravascular devices or hemodialysis.

Fungal infections are difficult to treat for several reasons. First, selective toxicity against fungal cells (and not the human host’s cells) is more difficult to achieve than for bacteria. Second, many antifungal agents suffer from problems with solubility, stability, and absorption. Third, fungi readily develop resistance.

For years, the mainstay of pharmacotherapy against systemic fungal infections has been the polyene class of drugs, especially amphotericin B. These drugs are toxic and azole agents (a different chemical class) have been developed as alternative antifungal drugs. However, owing to widespread use, azole-resistant organisms are becoming more widespread. Recently, the newest class of antifungals—the echinocandins—has demonstrated improved safety, efficacy, and tolerability.

Antifungals are generally classified on the basis of their target site of action. The major classes of antifungal agents—azoles,polyenes, echinocandins, and terbinafine—kill fungi by disrupting the synthesis or function of fungal cellular membranes. In contrast, the fungicidal actions of the less important agents, flucytosine and griseofulvin, are due to interference with intracellular functions (Figure 29–1 and 29–2). Clinically, antifungal drugs fall into several categories: drugs (oral or parenteral) for systemic infections, oral drugs for mucocutaneous infections (mucous membranes and skin), and topical drugs for mucocutaneous infections (Table 29–1).

###### Figure 29–1.

Fungal infections are difficult to treat, particularly in the immunocompromised patient. Most fungi are resistant to conventional antimicrobial agents, and only a few drugs are available for the treatment of systemic fungal ...

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