Environmental Terbinafine Contamination and Dermatophyte Resistance: A One Health Hypothesis in Need of Ecological Validation.

Abstract

Terbinafine resistance in dermatophytes is an increasing global concern, driven in part by the intercontinental spread of Trichophyton indotineae. The current epidemic of dermatophyte resistance is primarily attributed to clinical and community factors, including inappropriate antifungal use and fixed-dose corticosteroid-antifungal combinations. However, environmental antifungal contamination has emerged as a potential but largely unexplored contributor to resistance selection, as has been proposed for azole resistance in other fungal pathogens. Here, we examine whether environmental terbinafine contamination represents an overlooked One Health selection pressure or, alternatively, an exposure signal whose relevance to dermatophyte resistance remains ecologically constrained. Terbinafine is highly lipophilic, partitions into organic matter, and has been detected in wastewater, sludge, biosolids, surface water, groundwater, and sediment. Reported concentrations vary markedly by region and sample type, and in some cases exceed proposed resistance-selection thresholds. However, most clinically important dermatophytes, particularly anthropophilic Trichophyton lineages, are host-associated keratinophilic fungi rather than free-living environmental saprobes. Therefore, environmental terbinafine is unlikely to drive resistance unless viable dermatophyte propagules, keratinous substrates, and biologically active drug residues co-occur in the same ecological niche. Current evidence is insufficient to determine whether environmental terbinafine contamination contributes meaningfully to dermatophyte resistance selection. While infected wildlife and geophilic dermatophytes may serve as useful sentinel systems, they do not yet establish a causal environmental pathway for the emergence or spread of resistant T. indotineae. In order to address these knowledge gaps, we propose that future One Health surveillance should integrate terbinafine quantification with dermatophyte recovery, resistance-marker detection (i.e., SQLE screening), susceptibility testing, and experimental selection studies in biologically plausible reservoirs.