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,
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).
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 diseases. ...