Optimizing Topical Antifungal Therapy for Superficial Cutaneous Fungal Infections: Focus on Topical Naftifine for Cutaneous Dermatophytosis

patches or with multiple plaques, consideration needs to be given to Microsporum canis as the pathogen, most often from an infected cat.^16,25 Affected patients often have lesions on the face, arms, neck, and /or thighs, and possibly other skin sites, where inoculation has occurred due to contact with the infected feline source while holding it. In cases caused by M canis or other zoophilic fungi, the lesions are often more briskly inflammatory and do not always present with the classic picture of annular patches that are typically anticipated when considering tinea corporis in the differential diagnosis (Figure 5). A fungal culture should be obtained that allows for organism identification, and animal contact sources should be considered in such cases. Also, a DTM can be obtained as an inexpensive “screening culture medium” to initially support fungal colony growth (Figure 5).¹⁶ Once characteristic dermatophyte colonies grow on a DTM, this can then be sent to a qualified mycology laboratory to identify the dermatophyte genus and species.

Most SCFIs and CDIs are amenable to topical antifungal therapy,especially in immunocompetent patients.^3,6,9,16,17 Although a review of all available agents is beyond the scope of this article, the imidazoles, allylamines, and ciclopirox (a hydroxypyridone) are the most commonly used prescription agents in dermatology.^{3,5,6,17,19,26-28} The following is a focused review on topical naftifine for the treatment of SCFIs, especially DCIs.

Naftifine is an allylamine derivative formulated as a hydrochloride salt for topical administration in a 1% cream or gel, and more recently a 2% cream. Naftifine 1% gel (Naftin^® Gel) is approved by the United States Food and Drug Administration (FDA), and it is indicated for twice-daily topical application for the treatment of tinea pedis, tinea cruris, and tinea corporis caused by T rubrum, T mentagrophytes, T tonsurans, and E floccosum (recommended duration 3-4 weeks).²⁹ Naftifine 2% cream (Naftin^® Cream 2%) is FDA-approved with indication for once-daily treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by T rubrum in adult patients ≥18 years of age (2 weeks treatment duration).³⁰ Much of the clinical data collected on topical naftifine evaluated the 1% formulations once or twice daily, with once-daily shown overall to be equivalent in efficacy to twice-daily application for CDIs.^28-32 Additional studies are also available with the 2% cream formulation and are discussed later.

The following properties of naftifine have been reported and appear to be clinically relevant:

Naftifine exhibits in vitro fungicidal activity against a broad spectrum of organisms, including T rubrum, T mentagrophytes,T tonsurans, E floccosum, M canis, M audouini, and M gypseum, and also fungistatic activity against many Candida spp.^29-31 Naftifine clinical activity against staphylococcal and streptococcal pyodermas (n=30) has been demonstrated; however, it is not recommended that topical naftifine be used for the treatment of bacterial infections and such use is not FDA-approved.³³

The primary mechanism of action of topical naftifine is the arrest of fungal growth, increase in cell membrane fragility and permeability, accumulation of squalene, and disruption of the cell membrane. This occurs due to suppression of ergosterol biosynthesis via inhibition of squalene epoxidase, which differs from imidazole agents in being fungal sterol selective.^28-31 The observation of a more rapid onset of clinical improvement for CDIs, with topical naftifine vs imidazole antifungal agents, are likely related to the fungicidal effects of the former. However,reported anti-inflammatory properties may possibly be