Increasing Terbinafine Resistance in Danish Trichophyton Isolates 2019-2020

2019-2020 年丹麦毛癣菌分离株对特比萘芬的耐药性不断增加

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作者:Karen Marie Thyssen Astvad, Rasmus Krøger Hare, Karin Meinike Jørgensen, Ditte Marie Lindhardt Saunte, Philip Kjettinge Thomsen, Maiken Cavling Arendrup

Abstract

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. mentagrophytes/T. interdigitale SC for 19%. Approximately 60% of T. rubrum and T. mentagrophytes/interdigitale 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. mentagrophytes/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-resistant 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.

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