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Antifungal Resistance, Susceptibility Testing and Treatment of Recalcitrant Dermatophytosis Caused by Trichophyton indotineae: A North American Perspective on Management

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Abstract

There is an ongoing epidemic of chronic, relapsing dermatophytoses caused by Trichophyton indotineae that are unresponsive to one or multiple antifungal agents. Although this new species may have originated from the Indian subcontinent, there has been a notable increase of its reporting in other countries. Based on current literature, antifungal susceptibility testing (AFST) showed a large variation of terbinafine minimum inhibitory concentrations (MICs) (0.04 to ≥ 32 µg/ml). Elevated terbinafine MICs can be attributed to mutations in the squalene epoxidase gene (single mutations: Leu393Phe, Leu393Ser, Phe397Leu, and double mutations: Leu393Phe/Ala448Thr, Phe397Leu/Ala448Thr). Itraconazole MICs had a lower range when compared with that of terbinafine (0.008–16 µg/ml, with most MICs falling between 0.008 µg/ml and < 1 µg/ml). The interpretation of AFST results remains challenging due to protocol variations and a lack of established breakpoints. Adoption of molecular methods for resistance detection, coupled with AFST, may provide a better evaluation of the in vitro resistance status of T. indotineae. There is limited information on treatment options for patients with confirmed T. indotineae infections by molecular diagnosis; preliminary evidence generated from case reports and case series points to itraconazole as an effective treatment modality, while terbinafine and griseofulvin are generally not effective. For physicians working outside of endemic regions, there is currently an unmet need for standardized clinical trials to establish treatment guidelines; in particular, combination therapy of oral and topical agents (e.g., itraconazole and ciclopirox), as well as with other azoles (i.e., fluconazole, voriconazole, ketoconazole), warrants further investigation as multidrug resistance is a possibility for T. indotineae.

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  1. Division of Dermatology, Department of Medicine, University of Toronto School of Medicine, Toronto, ON, Canada

    Aditya K. Gupta

  2. Mediprobe Research Inc., 645 Windermere Road, London, ON, N5X 2P1, Canada

    Aditya K. Gupta, Shruthi Polla Ravi, Tong Wang & Elizabeth A. Cooper

  3. Bako Diagnostics, Alpharetta, GA, USA

    Sara A. Lincoln, Hui-Chen Foreman & Wayne L. Bakotic

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A.K.G., S.P.R., T.W. and E.A.C. have no competing interests to declare. S.A.L., H.F. and W.L.B. are employees of Bako Diagnostics (Alpharetta, GA).

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Conceptualization, AKG; Data Curation, SPR and TW; Formal Analysis, SPR and TW; Investigation, SPR and TW; Methodology; SPR and TW; Project Administration, AKG; Supervision, AKG and EAC; Validation, AKG and EAC; Visualization, SPR; Writing – Original Draft Preparation, SPR and TW; Writing – Review and Editing, AKG, TW, EAC, SAL, HF and WLB.

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Gupta, A.K., Polla Ravi, S., Wang, T. et al. Antifungal Resistance, Susceptibility Testing and Treatment of Recalcitrant Dermatophytosis Caused by Trichophyton indotineae: A North American Perspective on Management. Am J Clin Dermatol 24, 927–938 (2023). https://doi.org/10.1007/s40257-023-00811-6

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