A Textbook of Clinical Pharmacology and Therapeutics

●Antifungal drug therapy 340

●Antiviral drug therapy (excluding anti-HIV drugs) 344

●Interferons and antiviral hepatitis therapy 348

CHAPTER 45

45 Fungal and non-HIV viral infections

INFECTIONS

ANTIFUNGAL DRUG THERAPY

INTRODUCTION

Fungi, like mammalian cells but unlike bacteria, are eukary-
otic and possess nuclei, mitochondria and cell membranes.
However, their membranes contain distinctive sterols, ergo-
sterol and lanesterol. The very success of antibacterial therapy
has created ecological situations in which opportunistic fungal
infections can flourish. In addition, potent immunosuppres-
sive and cytotoxic therapies produce patients with seriously
impaired immune defences, in whom fungi that are non-
pathogenic to healthy individuals become pathogenic and
cause disease. Table 45.1 summarizes an approach to antifun-
gal therapy in immunocompromised patients. Sites of action
of antifungal drugs are summarized in Figure 45.1.

Table 45.1:An approach to antifungal drug therapy in the immunocompromised host

Fungal infection Drug therapy for superficial infection Drug therapy for deep-seated infection

Candida Nystatin – topical Amphotericin B with or without flucytosine

Clotrimazole – topical

Miconazole – topical Fluconazole – oral or i.v.

Fluconazole – oral Itraconazole or voriconazole oral

Caspofungin if failing azole therapy

Aspergillus Amphotericin B i.v. (liposomal)

Voriconazole or caspofungin if failing azole

therapy

Cryptococcus Amphotericin B plus flucytosine or fluconazole

i.v. (oral continuation therapy)

Disseminated histoplasmosis Itraconazole or amphotericin B i.v. (or

fluconazole)

Disseminated coccidiomycosis Fluconazole or amphotericin B i.v. (plus

flucytosine) or itraconazole

Blastomycosis Amphotericin B i.v. or itraconazole

Fungal cell

Amphotericin B and

nystatin bind with

ergosterol and

disrupt cell membrane

Fluconazole, other

azoles, and terbinafine

inhibit synthesis of

ergosterol and disrupt

cell membrane

Caspofungin inhibits

synthesis of glucan

and disrupts cell wall

Flucytosine inhibits

synthesis of fungal

DNA and RNA

Griseofulvin inhibits

cell division and

reproduction of

fungal cells

DNA and RNA

in nucleus

Ergosterol in

cell membrane

Glucan in

cell wall

Figure 45.1:Sites of action of antifungal drugs.