Global Emergence of Antifungal‐Resistant Dermatophytosis Caused by Trichophyton indotineae (Formerly T. mentagrophytesITS Genotype VIII): A Genomic Investigation Involving 14 Countries

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Abstract
Background and Objective: Trichophyton indotineae is a globally emerging, frequently antifungal‐resistant fungus causing severe dermatophytosis. To inform prevention efforts, we analysed the genomic epidemiology and resistance to terbinafine (first‐line oral antifungal) from a collection of multinational T. indotineae isolates collected from patients with clinically suspected dermatophytosis during 2016–2023.Methods: We performed whole genome sequencing and phylogenetic tree analysis based on single‐nucleotide polymorphisms (SNPs). T. indotineae phylogenetic results were correlated with patient demographic characteristics and isolate terbinafine susceptibility profiles that were determined by antifungal susceptibility testing and squalene epoxidase gene sequencing. Trichophyton mentagrophytes and Trichophyton interdigitale isolates from the USA, and Trichophyton rubrum isolates from three countries were added for contextual analysis.Results: Among 347 T. indotineae isolates, 227 (65%) were in vitro resistant to terbinafine. Countries represented were India (43%); Germany (21%); Bangladesh (8%); United States (8%); United Arab Emirates (7%); Iraq (5%); Finland (3%); Poland (2%); Austria, Canada, Cambodia, Estonia, Singapore, and Switzerland (each < 1%). Median SNP difference between isolates was 106 SNPs (range: 0–392). Clustering by age, sex, or country was not observed. One subcluster was composed of terbinafine‐resistant isolates with a specific squalene epoxidase gene mutation (F397L) and was widely dispersed among 10 countries. Intra‐species genomic diversity was greater among 19 T. rubrum isolates (260 SNPs [range: 73–1038]), or among 10 T. mentagrophytes/T. interdigitale isolates from the USA compared with the intra‐species diversity of the T. indotineae isolates.Conclusions: Our findings corroborate T. indotineae's recent emergence and ongoing international transmission and suggest the rapid spread of a subset of terbinafine‐resistant isolates. Continued efforts are necessary to mitigate this pathogen's spread.

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