New Oral Treatments for Dermatophytosis

The dermatophyte or ringworm fungi that cause disease in man belong to three genera, Trichophyton, Microsporum, and Epidermophyton. These organisms all invade the stratum corneum or keratinized structures derived from epidermis such as the hair or nails. The spectrum of clinical disease and the responses to treatment vary considerably with different species and sites of infection.' Generally, most of these infections respond satisfactorily to topical antifungal agents such as the imidazoles, but other compounds ranging from chlorphenesin to Whitfield's ointment are also effective. Oral therapy is normally reserved for treatment of recalcitrant infections such as the "dry-type'' or moccasin-type T rubrum infections, scalp ringworm (tinea capitis), and onychomycosis. The responses vary considerably. Previously published studies suggest that as few as 40% of patients receiving apparently adequate doses of griseofulvin for toenail infections, for instance, achieve long-term remission at the end of a prolonged course of therapy? Fingernails respond better, but therapy may have to be continued for unacceptably long periods. Although the responses of scalp ringworm to treatment are generally better, the minimum period of therapy is approximately 6 weeks-short treatment regimens for griseofulvin have been explored, however, and have been found to offer reasonable results.' The results of treatment with ketoconazole are similar, although there are some forms of dermatophytosis, such as tinea corporis due to T. rubrum or scalp ringworm due to T. tonsurans, in which the remission rate is better or faster' than with griseofulvin; on the other hand, the risk of hepatotoxicity, however slight, necessarily limits the use of ketoconazole in superficial mycoses. There is therefore a need for alternative methods of therapy in order to achieve better treatment responses in onychomycosis, in dry-type T. rubrum infections, and in certain other dermatophytoses. It would also be helpful to have an alternative to griseofulvin for other forms of infection. Whether it will ever be either possible or acceptable to use short courses of oral therapy in place of topically applied antifungals or to reduce the time for treating nail infections orally to periods of no more than 4 weeks, for instance, remains to be seen; at any rate, these are possible further uses of oral antidermatophyte drugs. The purpose of this paper is to evaluate the newest orally active antifungals in the light of these comments. The pharmacology and in vitro antifungal properties of these