The global emergence of Trichophyton indotineae: epidemiology, resistance, and management challenges

Dermatophytosis affects approximately 25% of the world population. Terbinafine, an antifungal medication, was historically used to treat this condition. However, the infection caused by a newer fungal species called Trichophyton indotineae has changed this situation, as it responds poorly to terbinafine. Moreover, the infection caused by this species lasts longer, returns repeatedly after treatment, and can spread over large areas of the body. This fungus was first linked to major recurrent and chronic skin infections in India and has now spread across the globe having been identified in Asia, the Middle East, Europe, and North America. The major concern is that this infection, caused by T. indotineae, may be spreading internationally, and carrying antifungal resistance, it could pose a serious global public health problem. This review discusses five main aspects of T. indotineae: taxonomic classification, epidemiology, mechanism of drug resistance, diagnostic limitations, and management challenges leading to treatment failure. The mechanism of action of terbinafine is to bind and block the fungal enzyme squalene epoxidase, which is required to produce ergosterol, a component of the cell membrane. In resistant strains, point mutations occur in the squalene epoxidase gene, particularly Leu393Phe and Phe397Leu, changing the structure of the enzyme, and terbinafine cannot bind effectively, leading to treatment failure and recurrence. Resistance to alternative drugs like itraconazole and other azoles is also increasing through the overexpression of efflux pumps. In addition, several clinical and public health problems, such as the increasing use of over-the-counter corticosteroid creams, species identification delays, household transmission, and limited public health surveillance, have also contributed to the spread and resistance of this fungal infection. There are several knowledge gaps. Addressing this threat by T. indotineae requires standardised laboratories with genetic testing to identify the species; treatment guided by susceptibility; antifungal stewardship that selects the appropriate antifungal drug, dose, and treatment duration; regulation of the use of combination drugs; international surveillance; and high-quality, multicentre RCTs to establish evidence-based dosing regimens.