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The Growing Problem of Antifungal Resistance in Onychomycosis and Other Superficial Mycoses

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Abstract

Superficial mycoses are becoming increasingly resistant to current antifungal medications. As alternative therapeutic options are limited, the increasing frequency of reports of antifungal resistance is alarming. This epidemic parallels the rise of antibiotic resistance; however, the significance of this problem has yet to gain global attention. Here, we discuss the reports of antifungal resistance from around the world, present our own experience with treatment-resistant infections, and examine alternative treatment strategies. The majority of reports of recalcitrant infections indicate terbinafine resistance as the causative factor. Single-point mutations in the squalene oxidase gene is the most reported mechanism of resistance to terbinafine. Mixed infections of dermatophytes with non-dermatophyte molds and/or yeasts are becoming more prevalent and contributing to the resistant nature of these infections. The key to selecting an effective antifungal therapy for a recalcitrant infection is identification of the infectious organisms(s) and testing susceptibility of the organism(s) to antifungal drugs. Combination and sequential therapy regimens are options, but both require active monitoring for hepatic and renal function, drug interactions, and other adverse effects. Selected topical antifungals with a wide spectrum of activity may also be considerations in some clinical presentations. Innovative treatment regimens and novel therapeutics are needed to overcome the rising epidemic of antifungal resistance.

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Authors and Affiliations

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

    Aditya K. Gupta, Helen J. Renaud & Emma M. Quinlan

  2. Division of Dermatology, Department of Medicine, University of Toronto School of Medicine, Toronto, Canada

    Aditya K. Gupta, Neil H. Shear & Vincent Piguet

  3. Division of Dermatology, Sunnybrook Health Sciences Centre, Toronto, Canada

    Neil H. Shear

  4. Division of Dermatology, Women’s College Hospital, Toronto, Canada

    Vincent Piguet

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Correspondence to Aditya K. Gupta.

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HJR and EMQ are employed by Mediprobe Research Inc., a not-for-profit, non-commercial research group and have no conflicts of interest that are directly relevant to the content of this article. AKG is a consultant for Bausch Health, Ortho Dermatologics, and Moberg Pharma; NHS has been a paid consultant to Alpha Laboratories, Canada & Bausch Health, Canada. VP has no personal financial ties with any pharmaceutical company. He undertakes advisory work for Pfizer, AbbVie, Janssen, UCB, Novartis, Almirall, and Celgene and has received honoraria from Kyowa Kirin Co., Ltd. In his role as Department Division Director of Dermatology at the University of Toronto, VP has received departmental support in the form of unrestricted educational grants from AbbVie, Bausch Health (formerly Valeant), Celgene, Janssen, LEO Pharma, Lilly, NAOS, Novartis, Pfizer, Pierre-Fabre, and Sanofi in the past 3 years.

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The manuscript was conceived by AKG; the work was drafted by HJR and substantively revised by AKG, EQ, NHS, and VP.

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Gupta, A.K., Renaud, H.J., Quinlan, E.M. et al. The Growing Problem of Antifungal Resistance in Onychomycosis and Other Superficial Mycoses. Am J Clin Dermatol 22, 149–157 (2021). https://doi.org/10.1007/s40257-020-00580-6

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