First report of terbinafine resistance in human dermatophytosis in Uruguay

Trichophyton rubrum and the Trichophyton mentagrophytes complex are the leading etiologic agents of human dermatophytosis. Terbinafine remains the first-line therapy for most dermatophyte infections; however, resistant strains have been increasingly reported worldwide, and the first cases of T. indotineae in Latin America have recently been reported. To update the limited regional information on Trichophyton spp. terbinafine resistance, we conducted a prospective laboratory study in Montevideo, Uruguay, from July 2023 to July 2024, using samples obtained through routine dermatological practice. Isolates were identified by morphological analysis and Matrix-Assisted Laser Desorption Ionisation-Time of Flight Mass Spectrometry (MALDI-TOF). Terbinafine-resistant (TerR) clinical isolates were screened with the terbinafine-containing agar medium (TCAM) method, and their minimal inhibitory concentrations (MICs) for terbinafine and itraconazole were determined using the European Committee for Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. The squalene epoxidase gene (SQLE) of TerR isolates was sequenced to detect resistance-associated mutations. Of 1252 processed samples, 543 were positive by microscopic examination and 281 by culture. Dermatophytes were identified in 231 of 281 positive cultures. The predominant species were T. rubrum (74.9%) and the T. mentagrophytes complex (19.9%), together accounting for 94.8% of isolates. Terbinafine susceptibility screening was performed on 171 isolates; 4 (2.34%) were resistant, with MICs ≥ 1 mg/l. Sequenced SQLE revealing amino acid substitutions at positions 393 or 397 in three T. rubrum and one T. mentagrophytes complex isolates. This study identifies the terbinafine resistance-associated mutations in Uruguay and highlights the urgent need for regional surveillance of this emerging phenomenon.