2026 Terbinafine Resistance Update: The Burden and Geographic Distribution of Antifungal-Resistant Dermatophytes in Nail Infections in the United States

Abstract

Introduction Fungal infections such as nail onychomycosis are common and can be difficult to treat. Additionally, resistance to systemic antifungal treatments, such as terbinafine, is increasing. This retrospective study assessed antifungal susceptibility of dermatophytes causing onychomycosis in the US and determined their geographical distribution.  Methods Organisms were identified from samples of infected nails collected from US podiatric/dermatologic clinics using potassium hydroxide/Calcofluor White testing, culture, and macroscopic profiling via scanning electron microscopy. Terbinafine- and efinaconazole-susceptibility were determined as minimum inhibitory concentration required to inhibit ≥80% of fungal growth relative to control (MIC). Terbinafine resistance was defined as MIC ≥0.5 µg/mL. Data were analyzed via descriptive statistics and nonparametric tests. Results From 2021-2025, 30 sites from 30 states provided patient isolates (n=620); most dermatophyte species were Trichophyton rubrum (94.0%). Efinaconazole antifungal activity against isolates was greater than terbinafine, as evidenced by lower MIC values (MIC inhibiting ≥90% of isolates: efinaconazole, 0.016 µg/mL; terbinafine, 0.031 µg/mL). Prevalence of terbinafine-resistant dermatophyte isolates was 4.4% (27/620) overall, and the proportion increased over time from 2021 (1.8% [2/110]) to 2025 (10.1% [14/138]). The highest proportion of resistant isolates were from Texas (19.1% [9/47]), California (18.4% [7/38]), and Minnesota (14.0% [7/50]). Efinaconazole showed robust activity against all tested isolates, including terbinafine-resistant ones, with most MICs ≤0.016 µg/mL (range, 0.002-0.25 µg/mL). Conclusions While no dermatophyte isolates were resistant to efinaconazole, rates of terbinafine-resistant isolates were greater than previously published estimates. Geographically, terbinafine resistance was highly clustered, producing regional resistance hot spots. Efinaconazole demonstrated potent antifungal activity against terbinafine-resistant dermatophytes, demonstrating its effectiveness against onychomycosis associated with terbinafine-resistant strains.