An update on antifungal resistance in dermatophytosis

ABSTRACT

Introduction

The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention.

Areas covered

This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.

Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent).

Expert opinion

Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.

KEYWORDS:

• Antifungal resistance
• antifungal susceptibility testing
• dermatophytes
• dermatophytosis
• onychomycosis
• squalene epoxidase mutations
• superficial fungal infections

Article highlights

• Fungal pathogens employ diverse resistance mechanisms to mitigate the impact of antifungal agents.

• Identifying the fungal pathogen responsible for onychomycosis and superficial dermatomycoses is essential for optimizing treatment, achievable through traditional testing (light microscopy and culture) and molecular methods.

• Even in the absence of defined clinical breakpoints for dermatophytes, antifungal susceptibility testing (AFST) remains the predominant approach for evaluating resistance.

• Some mutations in the SQLE gene are more frequently associated with clinical resistance to terbinafine than others.

• Therapeutic drug monitoring (TDM) for some antifungals may serve as an aid for determining optimal treatment dosages in dermatophytosis.

• The implementation of antifungal stewardship (AFS) is vital.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2024.2343079.

Additional information

Funding

This paper was not funded.