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

• Main Authors: Pietro Nenoff, Shyam B. Verma, Andreas Ebert, Anke Süß, Eleni Fischer, Elke Auerswald, Stephanie Dessoi, Wencke Hofmann, Simone Schmidt, Kathrin Neubert, Regina Renner, Sirius Sohl, Uta Hradetzky, Ursula Krusche, Hans-Christian Wenzel, Annegret Staginnus, Jörg Schaller, Valentina Müller, Christiane Tauer, Matthias Gebhardt, Katja Schubert, Zaid Almustafa, Rudolf Stadler, Andrea Fuchs, Cassian Sitaru, Carsten Retzlaff, Cora Overbeck, Thomas Neumann, Anette Kerschnitzki, Stephan Krause, Martin Schaller, Birgit Walker, Thomas Walther, Lars Köhler, Manuela Albrecht, Ursula Willing, Michel Monod, Karine Salamin, Anke Burmester, Daniela Koch, Constanze Krüger, Silke Uhrlaß
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Journal of Fungi
• Subjects: dermatophytoses; terbinafine-resistant; squalene epoxidase; point mutation; transmission; Itraconazole
• Online Access: https://www.mdpi.com/2309-608X/6/4/207
• ISSN: 2309-608X

Chronic recalcitrant dermatophytoses, due to <i>Trichophyton</i> (<i>T</i>.) <i>mentagrophytes</i> 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 <i>T</i>. <i>mentagrophytes</i> 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 <i>T</i>. <i>mentagrophytes</i> 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 <i>T</i>. <i>mentagrophytes</i> isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1-α)). All were identified as genotype VIII (India) of <i>T</i>. <i>mentagrophytes</i>. 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 <i>T</i>. <i>mentagrophytes</i> Type VIII are being increasingly isolated. In Germany, transmission of <i>T</i>. <i>mentagrophytes</i> Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.