Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany–“The Tip of the Iceberg?”

Journal of Fungi

卷:6

Birgit Walker¹  Martin Schaller¹  Anke Burmester²  Karine Salamin³  Michel Monod³  Jörg Schaller⁴  Cora Overbeck⁵  Thomas Neumann⁵  Sirius Sohl⁶  Regina Renner⁶  Christiane Tauer⁷  Kathrin Neubert⁸  Katja Schubert⁹  Eleni Fischer¹⁰  Simone Schmidt¹¹  Annegret Staginnus¹²  Lars Köhler¹³  Andrea Fuchs¹⁴  Uta Hradetzky¹⁵  Ursula Krusche¹⁵  Elke Auerswald¹⁶  Matthias Gebhardt¹⁷  Manuela Albrecht¹⁸  Ursula Willing¹⁸  Hans-Christian Wenzel¹⁹  Wencke Hofmann²⁰  Stephanie Dessoi²⁰  Anke Süß²¹  Valentina Müller²²  Zaid Almustafa²³  Anette Kerschnitzki²⁴  Carsten Retzlaff²⁵  Andreas Ebert²⁶  Pietro Nenoff²⁶  Silke Uhrlaß²⁶  Daniela Koch²⁶  Constanze Krüger²⁶  Stephan Krause²⁷  Thomas Walther²⁸  Rudolf Stadler²⁹  Cassian Sitaru³⁰  ShyamB. Verma³¹ 

[1] Department of Dermatology, University Clinic Tübingen, Liebermeisterstraße 25, 72076 Tübingen, Germany;

[2] Department of Dermatology, University Hospital Jena, Erfurter Str. 35, D-07743 Jena, Germany;

[3] Dermatology Service, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland;

[4] Dermatopathologie Duisburg, J. Schaller und C. Hendricks, 47166 Duisburg, Germany;

[5] Gemeinschaftspraxis Dermatologie Cora Overbeck und Thomas Neumann, Lange Str. 53, 34346 Hann. Münden, Germany;

[6] Gemeinschaftspraxis Dres. med. S. Sohl & R. Renner, Katharinenstr. 33, 73728 Esslingen, Germany;

[7] Hautarztpraxis Christiane Tauer, Marcel- Callo- Platz 4, 98544 Zella-Mehlis, Germany;

[8] Hautarztpraxis Dipl. med. Kathrin Neubert, Bertolt- Brecht-Straße 2, 09217 Burgstädt, Germany;

[9] Hautarztpraxis Dresden, Loschwitzer Straße 40, D-01309 Dresden, Germany;

[10] Hautarztpraxis Gunhild Kratzsch, Kochstraße 66, 04275 Leipzig, Germany;

[11] Hautarztpraxis im MVZ Friedrichstadt, Friedrichstraße 41, Haus A-Haupteingang-1. OG, 01067 Dresden, Germany;

[12] Hautarztpraxis, 04668 Grimma, Germany;

[13] Hautarztpraxis, Boppstr. 20-24, 55118 Mainz, Germany;

[14] Hautarztpraxis, Darwinstr. 1, 04600 Altenburg, Germany;

[15] Hautarztpraxis, Landsberger Straße 4, 04157 Leipzig, Germany;

[16] Hautarztpraxis, Lungwitzer Straße 30, 09337 Hohenstein-Ernstthal, Germany;

[17] Hautarztpraxis, Matthias Gebhardt, Leipziger Str. 90, 08058 Zwickau, Germany;

[18] Hautarztpraxis, Mockauer Str. 123-125, 04357 Leipzig, Germany;

[19] Hautarztpraxis/Phlebologie, Waldkerbelstraße 12, 04329 Leipzig, Germany;

[20] Hautzentrum Nordwest, Tituscorso 2-6, 60439 Frankfurt am Main, Germany;

[21] Hautärztin, Gemeinschaftspraxis Allgemeinmedizin und Dermatologie, Kurfürstenstraße 23 a, 54616 Wittlich, Germany;

[22] Helios Klinikum Duisburg, Klinik für Dermatologie, Allergologie und Phlebologie, 47166 Duisburg, Germany;

[23] Klinik für Dermatologie, Charite, 10117 Berlin, Germany;

[24] Klinik für Dermatologie, Klinikum Uni München, Mykologisches Labor, Frauenlobstr. 9-11, 80337 München, Germany;

[25] Labor Dres. Löbel und Retzlaff, Felsbachstr. 5, 07745 Jena, Germany;

[26] Labor für Medizinische Mikrobiologie, 04571 Rötha OT Mölbis, Germany;

[27] Stephan Krause, Bundeswehrkrankenhaus Berlin, Klinik III Dermatologie, Scharnhorststraße 13, 10115 Berlin, Germany;

[28] Thomas Walther, Hautarztpraxis, Bästleinstr. 6, 04347 Leipzig, Germany;

[29] Universitätsklinik für Dermatologie, Venerologie, Allergologie und Phlebologie, Johannes Wesling Klinikum Minden, Hans-Nolte-Straße 1, D-32429 Minden, Germany;

[30] Universitätsklinikum Freiburg, Klinik für Dermatologie und Venereologie, Mykologisches Labor, Hauptstraße 7, 79104 Freiburg, Germany;

[31] “Nirvan” and “In Skin” Clinics, Vadodara, 390020 Gujarat, India;

关键词: dermatophytoses;    terbinafine-resistant;    squalene epoxidase;    point mutation;    transmission;    Itraconazole;   

DOI  :  10.3390/jof6040207

来源: DOAJ

【 摘 要 】

Chronic recalcitrant dermatophytoses, due to Trichophyton (T.) mentagrophytes Type VIII are on the rise in India and are noteworthy for their predominance. It would not be wrong to assume that travel and migration would be responsible for the spread of T. mentagrophytes Type VIII from India, with many strains resistant to terbinafine, to other parts of the world. From September 2016 until March 2020, a total of 29 strains of T. mentagrophytes Type VIII (India) were isolated. All patients were residents of Germany: 12 females, 15 males and the gender of the remaining two was not assignable. Patients originated from India (11), Pakistan (two), Bangladesh (one), Iraq (two), Bahrain (one), Libya (one) and other unspecified countries (10). At least two patients were German-born residents. Most samples (21) were collected in 2019 and 2020. All 29 T. mentagrophytes isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1-α)). All were identified as genotype VIII (India) of T. mentagrophytes. In vitro resistance testing revealed 13/29 strains (45%) to be terbinafine-resistant with minimum inhibitory concentration (MIC) breakpoints ≥0.2 µg/mL. The remaining 16 strains (55%) were terbinafine-sensitive. Point mutation analysis revealed that 10/13 resistant strains exhibited Phe³⁹⁷Leu amino acid substitution of squalene epoxidase (SQLE), indicative for in vitro resistance to terbinafine. Two resistant strains showed combined Phe³⁹⁷Leu and Ala⁴⁴⁸Thr amino acid substitutions, and one strain a single Leu³⁹³Phe amino acid substitution. Out of 16 terbinafine-sensitive strains, in eight Ala⁴⁴⁸Thr, and in one Ala⁴⁴⁸Thr +, new Val⁴⁴⁴ Ile amino acid substitutions were detected. Resistance to both itraconazole and voriconazole was observed in three out of 13 analyzed strains. Treatment included topical ciclopirox olamine plus topical miconazole or sertaconazole. Oral itraconazole 200 mg twice daily for four to eight weeks was found to be adequate. Terbinafine-resistant T. mentagrophytes Type VIII are being increasingly isolated. In Germany, transmission of T. mentagrophytes Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.

【 授权许可】

Unknown