In Vitro Terbinafine Response and Minimum Inhibitory Concentration-Squalene Epoxidase Mutation Correlation in Tinea...

Chronic and recalcitrant dermatophytosis has become an increasing therapeutic challenge, particularly in India, where widespread antifungal misuse and environmental factors contribute to persistent infections. This study investigated the clinical patterns, antifungal susceptibility, and molecular mechanisms underlying terbinafine resistance in patients with tinea corporis and tinea cruris. A total of 105 clinically diagnosed and KOH-positive patients were enrolled. The majority were male (60%) with a mean age of 34 years and an average disease duration of 13 months. Most cases involved multiple sites, with the groin, thighs, and buttocks most frequently affected. Phenotypic and molecular identification revealed Trichophyton mentagrophytes/interdigitale complex (Tm/TiC) as the predominant pathogen (97%), followed by rare isolates of Trichophyton rubrum (2%) and Trichophyton indotineae (1%). Antifungal susceptibility testing (CLSI M38-A2) showed high MIC values for fluconazole (MIC₅₀/₉₀: 64 µg/ml), terbinafine (MIC₅₀: 0.5 µg/ml, MIC₉₀: 16 µg/ml), and griseofulvin (MIC₅₀: 2 µg/ml, MIC₉₀: 8 µg/ml), while itraconazole exhibited the best in vitro activity (MIC₅₀: 0.25 µg/ml, MIC₉₀: 0.5 µg/ml). Notably, 33% of isolates demonstrated high terbinafine MICs (≥ 1 µg/ml). SQLE gene sequencing identified mutations, particularly F397L, strongly associated with elevated terbinafine MICs and prior drug exposure. These findings highlight the alarming rise of terbinafine resistance among dermatophytes and underscore the role of inappropriate antifungal use in driving resistance. Regular antifungal susceptibility testing, careful drug selection based on prior exposure, and strict patient compliance are essential for improving outcomes. Until clinical breakpoints are established, treatment should be continued until both clinical and mycological cure are achieved.