Terbinafine and itraconazole resistance in dermatophytes

Abstract

Terbinafine-resistant dermatophytes in patients were exceptional before the second decade of this century. However, acquired resistance to commonly used antifungal compounds has recently emerged in several countries. Resistance towards terbinafine is generated by missense mutations in the squalene epoxidase enzyme targeted by the drug, while recorded resistance towards azoles is due to the overexpression of genes encoding multidrug transporters of the ABC family. At present, approximately 1% of Trichophyton rubrum isolates from Tinea pedis and onychomycosis in Switzerland are resistant to terbinafine. Terbinafine-resistant T. rubrum was also isolated from extended Tinea corporis in patients more susceptible to fungal infections and requiring continuous treatment. Repeated topical and systemic treatments with terbinafine have likely contributed to the development of terbinafine resistance in patients. The prevalence of T. rubrum resistant to terbinafine in Europe contrasts with that of resistant Trichophyton mentagrophytes isolates in India (30-70%). If drugs on the open market and overmedication can partly explain this alarming situation, several indications also allow the suspicion of an origin linked to environmental problems.