In Vitro Susceptibility and Molecular Docking of Echinocandins Against Clinical Dermatophyte Isolates: Implications for Resistant Dermatophytosis

Drug-resistant dermatophytosis has emerged as a global therapeutic challenge, underscoring the need for alternative antifungal strategies. Echinocandins, inhibitors of β-(1,3)-D-glucan synthase, demonstrate potent activity against Candida and Aspergillus but remain insufficiently characterized against dermatophytes. This study evaluated the in vitro activity of anidulafungin and caspofungin in a diverse clinical collection and examined their predicted interactions with β-(1,3)-D-glucan synthase. Antifungal susceptibility testing was performed on 105 clinical isolates, including T. indotineae, T. mentagrophytes, T. rubrum, T. tonsurans, M. canis, N. gypsea, and T. violaceum, using CLSI M38-A3 broth microdilution. Minimum effective concentrations (MECs) for echinocandins and minimum inhibitory concentrations (MICs) for comparator agents were determined. Molecular docking simulations were conducted to characterize echinocandin interactions with β-(1,3)-D-glucan synthase. Statistical analyses used Kruskal–Wallis and Dunn’s tests. Both echinocandins showed significantly lower MEC/MIC distributions than all comparator antifungals after adjustment for multiple comparisons (all adjusted p < 0.001). Anidulafungin was more potent than caspofungin (GM MECs: 0.011 vs. 0.022 µg/mL; p < 0.001). Against terbinafine-resistant T. indotineae, MEC50 values were 0.008 µg/mL (anidulafungin) and 0.016 µg/mL (caspofungin), markedly outperforming terbinafine (MIC50 = 4 µg/mL). Docking analyses demonstrated species- and ligand-dependent predicted interaction patterns with β-(1,3)-D-glucan synthase, providing complementary structural context for the observed in vitro susceptibility profiles. This study extends prior in vitro observations by profiling two echinocandins against diverse clinical dermatophytes, including terbinafine-resistant T. indotineae. Docking analysis provides structural context but does not establish target engagement. Further preclinical studies are needed to confirm therapeutic relevance.