Terbinafine resistance in Trichophyton mentagrophytes and Trichophyton rubrum in the Czech Republic: A prospective multicentric study

Author:

Kolarczyková Daniela1,Lysková Pavlína2,Švarcová Michaela34,Kuklová Ivana5,Dobiáš Radim67,Mallátová Naďa8,Kolařík Miroslav3,Hubka Vit13ORCID

Affiliation:

1. Department of Botany, Faculty of Science Charles University Prague Czech Republic

2. Department of Medical Microbiology Prague and Kladno Public Health Institute in Ústí nad Labem Prague Czech Republic

3. Laboratory of Fungal Genetics and Metabolism, Institute of Microbiology Czech Academy of Sciences Prague Czech Republic

4. Department of Genetics and Microbiology, Faculty of Science Charles University Prague Czech Republic

5. Department of Dermatology and Venereology, First Faculty of Medicine Charles University and General University Hospital in Prague Prague Czech Republic

6. Department of Bacteriology and Mycology Public Health Institute Ostrava Ostrava Czech Republic

7. Institute of Laboratory Medicine, Faculty of Medicine University of Ostrava Ostrava Czech Republic

8. Laboratory of Mycology and Parasitology Hospital České Budějovice České Budějovice Czech Republic

Abstract

AbstractBackgroundTerbinafine, an allylamine antifungal, is crucial for treating dermatophytosis by inhibiting squalene epoxidase (SQLE) in the ergosterol biosynthetic pathway. However, resistance is emerging, particularly in India and Southeast Asia, but reports of resistance spread worldwide. Despite this, comprehensive studies on terbinafine resistance in Trichophyton are still limited.ObjectivesThis research aimed to determine the prevalence of terbinafine resistance in the Czech Republic, with a focus on Trichophyton rubrum and Trichophyton mentagrophytes, and investigate the underlying molecular mechanisms.Patients/MethodsA total of 514 clinical strains of T. rubrum and 240 T. mentagrophytes collected from four Czech clinical institutions were screened for terbinafine resistance. Molecular investigations included DNA sequencing, specifically the ITS rDNA region and SQLE gene, as well as antifungal susceptibility testing following EUCAST guidelines.ResultsWhile no resistance was observed in T. rubrum, 2.5% of T. mentagrophytes strains exhibited resistance, marked by the F397L mutation in SQLE. Notably, resistance surged from 1.2% in 2019 to 9.3% in 2020 but reverted to 0% in 2021. All resistant strains were identified as T. mentagrophytes var. indotineae. Resistant strains exhibited high MICs for terbinafine (≥4 mg L−1) but low MICs to the other seven antifungals tested except for fluconazole.ConclusionsThis study highlights the emergence of terbinafine‐resistant T. mentagrophytes strains in the Czech Republic, with the F397L mutation being pivotal. Due to the relatively low resistance level, the current guidelines for dermatomycosis treatment in the Czech Republic remain effective, but ongoing surveillance is essential for timely adaptations if resistance patterns change.

Publisher

Wiley

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