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

Am J Clin Dermatol. 2021 Mar;22(2):149-157. doi: 10.1007/s40257-020-00580-6. Epub 2020 Dec 22.

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.

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Arthrodermataceae / drug effects
  • Arthrodermataceae / isolation & purification*
  • Drug Monitoring
  • Drug Resistance, Fungal
  • Drug Therapy, Combination / methods
  • Foot Dermatoses / drug therapy*
  • Foot Dermatoses / microbiology
  • Hand Dermatoses / drug therapy*
  • Hand Dermatoses / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • Onychomycosis / drug therapy*
  • Onychomycosis / microbiology
  • Terbinafine / pharmacology
  • Terbinafine / therapeutic use
  • Treatment Outcome

Substances

  • Antifungal Agents
  • Terbinafine