TY - JOUR

T1 - Increasing Terbinafine Resistance in Danish Trichophyton Isolates 2019–2020

AU - Astvad, Karen Marie Thyssen

AU - Hare, Rasmus Krøger

AU - Jørgensen, Karin Meinike

AU - Saunte, Ditte Marie Lindhardt

AU - Thomsen, Philip Kjettinge

AU - Arendrup, Maiken Cavling

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - Terbinafine resistance in Trichophyton species has emerged and appears to be increasing. A new EUCAST susceptibility testing method and tentative ECOFFs were recently proposed for Trichophyton. Terbinafine resistance and target gene mutations were detected in 16 Danish isolates in 2013–2018. In this study, samples/isolates submitted for dermatophyte susceptibility testing 2019– 2020 were examined. Species identification (ITS sequencing for T. mentagrophytes/T. interdigitale species complex (SC) isolates), EUCAST MICs and squalene epoxidase (SQLE) profiles were obtained. Sixty-three isolates from 59 patients were included. T. rubrum accounted for 81% and T. men-tagrophytes/T. interdigitale SC for 19%. Approximately 60% of T. rubrum and T. mentagrophytes/inter-digitale SC isolates were terbinafine non-wildtype and/or had known/novel SQLE mutations with possible implications for terbinafine MICs. All infections with terbinafine-resistant T. men-tagrophytes/interdigitale SC isolates were caused by Trichophyton indotineae. Compared to 2013–2018, the number of patients with terbinafine-resistant Trichophyton isolates increased. For T. rubrum, this is partly explained by an increase in number of requests for susceptibility testing. Terbinafine-re-sistant T. indotineae was first detected in 2018, but accounted for 19% of resistance (4 of 21 patients) in 2020. In conclusion, terbinafine resistance is an emerging problem in Denmark. Population based studies are warranted and susceptibility testing is highly relevant in non-responding cases.

AB - Terbinafine resistance in Trichophyton species has emerged and appears to be increasing. A new EUCAST susceptibility testing method and tentative ECOFFs were recently proposed for Trichophyton. Terbinafine resistance and target gene mutations were detected in 16 Danish isolates in 2013–2018. In this study, samples/isolates submitted for dermatophyte susceptibility testing 2019– 2020 were examined. Species identification (ITS sequencing for T. mentagrophytes/T. interdigitale species complex (SC) isolates), EUCAST MICs and squalene epoxidase (SQLE) profiles were obtained. Sixty-three isolates from 59 patients were included. T. rubrum accounted for 81% and T. men-tagrophytes/T. interdigitale SC for 19%. Approximately 60% of T. rubrum and T. mentagrophytes/inter-digitale SC isolates were terbinafine non-wildtype and/or had known/novel SQLE mutations with possible implications for terbinafine MICs. All infections with terbinafine-resistant T. men-tagrophytes/interdigitale SC isolates were caused by Trichophyton indotineae. Compared to 2013–2018, the number of patients with terbinafine-resistant Trichophyton isolates increased. For T. rubrum, this is partly explained by an increase in number of requests for susceptibility testing. Terbinafine-re-sistant T. indotineae was first detected in 2018, but accounted for 19% of resistance (4 of 21 patients) in 2020. In conclusion, terbinafine resistance is an emerging problem in Denmark. Population based studies are warranted and susceptibility testing is highly relevant in non-responding cases.

KW - Dermatophyte resistance

KW - SQLE

KW - Squalene epoxidase

KW - Terbinafine

KW - Trichophtyon mentagrophytes

KW - Trichophyton benhamiae

KW - Trichophyton indotineae

KW - Trichophyton interdigitale

KW - Trichophyton rubrum

U2 - 10.3390/jof8020150

DO - 10.3390/jof8020150

M3 - Journal article

C2 - 35205904

AN - SCOPUS:85123749596

VL - 8

JO - Journal of Fungi

JF - Journal of Fungi

SN - 2309-608X

IS - 2

M1 - 150

ER -