++
AT-A-GLANCE
Topical agents should be used for superficial fungal infections of limited extent.
Topical agents have the advantage of low cost, nonprescription availability, ease of use, and high patient compliance.
Topical antifungals include imidazoles, allylamines, benzylamines, polyenes, and ciclopirox.
A number of new carrier vehicles have been investigated to improve the bioavaliabilty of topical antifungals.
Systemic agents should be used to treat onychomycosis and tinea capitis, or when superficial fungal infection affects a large surface area.
Attention should be paid to drug–drug interactions when prescribing systemic antifungals.
Combination therapy with topical and systemic drugs presents several advantages.
+++
INTRODUCTION/BACKGROUND
++
Superficial mycoses, caused mainly by dermatophytes and yeast, are among the most frequent infections worldwide, affecting approximately 20% to 25% of the world’s population.1 Topical antifungals are the preferred option for the treatment of most of these infections, achieving high patient compliance. Moreover, many topical drugs have additional antibacterial action, which is beneficial in cases of superimposed bacterial infections. Further, many also possess antiinflammatory properties, which are advantageous in minimizing the effects of the host local inflammatory reactions to mycotic infection.2 Systemic antifungals are the mainstay treatment of tinea capitis and onychomycosis; also, dermatologists tend to reserve them for extensive, recurrent, or recalcitrant dermatomycosis.3,4 Despite the diversity in the structure of the fungal cell membrane and the unique existence of the mycotic cell wall compared to mammalian cells, the similarities in the metabolic profile between both kingdoms allow for limited numbers of organism-specific targets. Overall, the main target of both systemic and topical antifungals is ergosterol (Fig. 188-1), the fundamental mycotic cell membrane sterol. As of this writing, the 3 main antifungal categories targeting ergosterol are (1) allylamines and benzylamines, (2) azoles (imidazole and triazoles), and (3) polyenes. Whereas allylamines, benzylamines, and azoles block the biosynthesis of ergosterol, polyenes bind the molecule with high affinity, creating cell membrane pores. Other systemic antifungal agents (griseofulvin and flucytosine) act on intracellular structures via mechanisms similar to cancer chemotherapeutic agents.5,6 Although both are clinically effective, azoles exhibit superior activity against yeasts compared to allylamines, but less activity against dermatophytes.7 Although the most common adverse effects associated with topical therapy are mild, transient, and localized hypersensitivity skin reactions, systemic antifungals demonstrate various degrees of organ toxicity and possible serious drug interactions.3 This chapter aims to discuss the main topical and systemic antifungal agents currently in clinical use (Tables 188-1, 188-2, 188-3, 188-4).
++++