Patterns of Dermatophytosis and Antifungal Resistance: A Prospective Clinico-Mycological Study
Background: Dermatophytosis—superficial fungal infection caused by dermatophyte genera Trichophyton, Microsporum, and Epidermophyton—is among the most prevalent infectious dermatoses worldwide, with a markedly increasing burden in South Asia over the past decade. A concurrent epidemic of treatment-refractory, recurrent tinea infections has been attributed to the emergence of antifungal resistance, particularly terbinafine resistance mediated by mutations in the squalene epoxidase gene (SQLE). The drivers, epidemiology, and clinical correlates of resistance in Indian populations remain incompletely characterized. Objective: To determine the clinico-epidemiological patterns of dermatophytosis, identify prevalent causative species, characterize antifungal susceptibility profiles, detect SQLE resistance mutations, and identify risk factors associated with antifungal resistance in patients attending a tertiary dermatology center in Telangana, India. Methods: This prospective clinico-mycological study enrolled 210 consecutive patients with culture-confirmed dermatophytosis at Shadan Institute of Medical Sciences, Teaching Hospital & Research Centre, Hyderabad between February 2013 and January 2014. Dermatophyte species were identified by morphological and molecular methods. Minimum inhibitory concentrations (MICs) were determined by broth microdilution (EUCAST EDef 9.3). SQLE gene sequencing was performed for terbinafine-resistant isolates (MIC >0.5 µg/mL). Clinical outcomes were assessed at 4 weeks and 3 months. Multivariate logistic regression identified independent predictors of antifungal resistance. Results: Trichophyton mentagrophytes complex (39.0%) and T. rubrum (32.4%) were the predominant species. Terbinafine resistance was detected in 31.7% of T. mentagrophytes and 16.2% of T. rubrum isolates. Fluconazole demonstrated the lowest in vitro activity across all species. SQLE mutations (F397L, L393F, H440Y, A448T) were identified in 86.4% of high-level terbinafine-resistant isolates. Prior terbinafine exposure (adjusted OR 4.24), topical corticosteroid misuse (OR 3.12), and recurrent disease (OR 2.47) were the strongest independent predictors of resistance. Voriconazole demonstrated superior in vitro activity against resistant isolates. Conclusion: Antifungal resistance, particularly terbinafine resistance driven by SQLE mutations in T. mentagrophytes, is a major and growing therapeutic challenge in India. Topical steroid misuse and irrational antifungal prescribing are modifiable drivers that demand urgent regulatory and educational interventions. Routine susceptibility testing should be incorporated into the management of recurrent or treatment-refractory dermatophytosis.