EMERGING ANTIFUNGAL RESISTANCE IN DERMATOPHYTES: A COMPREHENSIVE REVIEW OF MECHANISMS, CHALLENGES, AND FUTURE THERAPEUTIC APPROACHES

Abstract

Antifungal resistance among dermatophytes is increasing, posing a significant challenge to the effective management of superficial fungal infections (SFIs). Dermatophyte species responsible for numerous cutaneous infections have developed resistance to commonly used antifungal agents, resulting in treatment failure and persistent disease. This review provides a comprehensive analysis of the mechanisms underlying antifungal resistance in dermatophytes, including genetic mutations, overexpression of efflux pumps, and biofilm formation, all of which contribute to diminished drug efficacy. Terbinafine remains the first-line therapeutic agent for dermatophyte infections; however, reports of terbinafine resistance have risen, particularly in strains of Trichophyton rubrum and Trichophyton indotineae. Resistance to azoles—especially itraconazole and fluconazole—has also emerged as a growing concern. Key resistance mechanisms involve mutations in genes such as ERG11 (lanosterol 14α-demethylase), CYP51, and squalene epoxidase, which play essential roles in ergosterol biosynthesis and thus represent critical targets for antifungal therapy. Additionally, the review examines host–pathogen interactions, highlighting how immune-evasion strategies employed by dermatophytes, along with host genetic factors, contribute to increased infection severity. Potential strategies to counter antifungal resistance are also discussed, including combination therapies, the development of novel antifungal agents, and host-directed treatment approaches. Understanding the molecular basis of resistance and the dynamics of host immunity is crucial for the development of more effective and targeted therapeutic interventions. This review underscores the need for continued research and innovation in antifungal therapy to address the growing problem of dermatophyte resistance.