Overview of Resistance Mechanisms in Dermatophytosis, Pharmacology and Uses of Fosravuconazole and Its Place in Potential Treatment Options for Trichophyton indotineae

Background: Dermatophytosis has evolved into a major therapeutic challenge with the global emergence of Trichophyton indotineae, a pathogen associated with chronic, recurrent, and treatment-refractory infections. The widespread emergence of antifungal resistance, particularly to terbinafine and, increasingly, itraconazole, has substantially limited effective systemic treatment options. Terbinafine resistance, primarily mediated by mutations in the squalene epoxidase (SQLE) gene (Erg1), including Phe397Leu, Leu393Phe, and Leu393Ser, has been reported in 17–75% of isolates, whereas reduced itraconazole susceptibility has reached 25–37% in selected cohorts from endemic regions. Objective: The present review examines the existent global resistance to Trichophyton indotineae, its mechanisms, measures that can be used to circumvent it, and the possible treatment options, with particular emphasis on the role of a novel azole fosravuconazole L-lysine ethanolate (F-RVCZ). Methods: The following bibliographic databases were searched from 2018 to June 2026: PubMed, Embase, Web of Science, and Cochrane Library databases using the key words fosravuconazole AND dermatophytosis, T. indotineae, resistance mechanisms, treatment, and synergy. Results: The established resistance mechanisms in T. indotineae are mutations in the Erg1 gene leading to alteration of the SQLE protein. Mutations of Erg11 are also reported and there is evidence that overexpression of efflux pumps may also be a compensatory mechanism leading to resistance to multiple currently used antifungals. While several agents have demonstrated in vitro efficacy, and experimental approaches targeting efflux pumps, kinases, and heat-shock proteins may be explored, the development of novel antifungal agents and rational antifungal drug combinations currently remain the most pragmatic strategies to manage recalcitrant dermatophytosis. Conclusions: While there is extensive data on resistance mechanisms, data on novel drugs that subvert or transcend these mechanisms are scant. There is a need for novel drugs or drug combinations to treat recalcitrant dermatophytosis, based on a priori laboratory data, and synergy studies. Clinical evidence for the use of F-RVCZ is in onychomycosis, with some data on utility in tinea pedis, tinea capitis, tinea barbae, eumycetoma, and selected subcutaneous mycoses. Real-world studies suggest an acceptable safety profile with mild and reversible laboratory abnormalities. Although available minimum inhibitory concentration data suggest it may be a feasible option in dermatophytosis, further in vitro susceptibility studies and clinical data from endemic areas facing rampant T. indotineae infections are required to explore its possible use in cutaneous dermatophytic infections.