Clinical Management of Antifungal-Resistant Dermatophytosis in Japan

Dermatophytosis remains one of the most common superficial fungal infections worldwide, and antifungal-resistant strains have recently emerged as an increasing clinical concern. In Japan, the prevalence of terbinafine-resistant Trichophyton species is currently estimated to be 2%, with most isolates harboring squalene epoxidase (SQLE) gene mutations such as Leu393Phe and Phe397Leu. This review summarizes recent epidemiological findings and representative clinical cases to illustrate the practical management strategies for antifungal-resistant dermatophytosis in Japan. Three illustrative cases were presented. Case 1 involved Trichophyton interdigitale carrying a Phe397Leu mutation that was unresponsive to terbinafine but was successfully treated with topical efinaconazole and luliconazole. Case 2 described a cluster infection of terbinafine-resistant Trichophyton rubrum (Leu393Phe) in a group home, where oral fosravuconazole achieved complete cure. Case 3 reported five soldiers with terbinafine-resistant dermatophytosis caused by Phe397Leu or Phe415Ile mutations, which were likely associated with prolonged topical SQLE inhibitor use. Resistance is often induced by the long-term or intermittent application of SQLE inhibitors, including over-the-counter topical terbinafine and butenafine. For suspected terbinafine-resistant infections, non-SQLE azoles, such as luliconazole and lanoconazole, are recommended because of their 10- to 100-fold increased activity against Trichophyton species. Oral fosravuconazole and topical agents such as 10% efinaconazole or 5% luliconazole have proven effective for onychomycosis. Ongoing surveillance, appropriate antifungal stewardship, and timely adjustment of treatment regimens are essential to prevent the further spread of antifungal-resistant dermatophytosis.