Abstract / Summary
Background: Dermatophyte infections, including onychomycosis, affect millions worldwide. Terbinafine, an allylamine antifungal, remains a foundational method of treatment. Objective: We aim to evaluate the in vitro antifungal susceptibility of terbinafine against dermatophyte isolates obtained from patients participating in a Phase III onychomycosis clinical trial. Methods: A total of 506 viable dermatophyte baseline isolates were tested using the Clinical and Laboratory Standard Institute (CLSI) M38-A3 broth microdilution method. The minimum inhibitory concentration (MIC) distributions in baseline isolates were compared between isolates from patients who were randomized and treated (group 1: terbinafine, n = 218 and vehicle, n = 108) and isolates from patients who screen-failed and therefore were not treated (group 2, n = 180). In addition, baseline MICs from group 1 were linked to their end-of-study mycological cure (negative KOH microscopy and negative fungal culture) to determine the relationship between MICs and mycological cure in study patients. Results: Terbinafine demonstrated potent antifungal activity with an overall MIC range of 0.001 to ≥0.5 µg/mL, MIC50 of 0.008 µg/mL, and MIC90 of 0.016 µg/mL. MIC distributions were comparable between group 1 and group 2 isolates (p = 0.98). Mycological cure was achieved across the full range of baseline MIC values. Only 16 isolates (3.2%) exhibited elevated MIC values (≥0.5 µg/mL). Of these, five were from terbinafine-treated patients, of whom three had evaluable end-of-study mycology results; two of these three patients achieved mycological cure, providing preliminary evidence that elevated in vitro MIC may not preclude clinical response to topical terbinafine. To our knowledge, this is the first reported analysis linking individual baseline MIC values to mycological cure for topical terbinafine and suggests that the high local nail concentrations achieved by the topical formulation may exceed the MIC threshold for isolates with reduced susceptibility.