National Belgian Study on Terbinafine Resistance in Trichophyton interdigitale/mentagrophytes/indotineae (2022-2023): Epidemiology and Molecular Features.

Abstract

Objectives: Trichophyton indotineae, a dermatophyte closely related to T. interdigitale and T. mentagrophytes, is of growing concern due to its high terbinafine resistance and widespread presence in India. Its emergence in Europe calls for enhanced surveillance. Resistance is linked to mutations in the squalene epoxidase (SQLE) gene. This multicentric national study aimed to evaluate the prevalence, terbinafine susceptibility, and phylogenomics of T. interdigitale/mentagrophytes/indotineae strains in Belgium, with a focus on SQLE substitutions. Methods: Between February 2022 and April 2023, 137 isolates from 16 Belgian labs were analyzed for antifungal susceptibility using the EUCAST E.Def.11.0 method. Whole-genome sequencing (WGS) was performed via Illumina sequencing method. Results: Phylogenomic analysis identified 8 T. indotineae, 91 T. interdigitale, and 38 T. mentagrophytes (including 7 genotype VII strains). Terbinafine resistance (5.1%) was mainly found in T. indotineae (87.5%), always linked to SQLE substitutions. T. interdigitale was fully susceptible. T. mentagrophytes showed mildly elevated MICs, often associated with K276N substitution. Conclusions: Terbinafine-resistant T. indotineae is emerging in Belgium, mostly via imported cases. Continued molecular surveillance and species-specific treatment strategies are essential.