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

ABSTRACT: 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.

SUBMITTER: Nenoff P

PROVIDER: S-EPMC7712673 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Nenoff Pietro P Verma Shyam B SB Ebert Andreas A Süß Anke A Fischer Eleni E Auerswald Elke E Dessoi Stephanie S Hofmann Wencke W Schmidt Simone S Neubert Kathrin K Renner Regina R Sohl Sirius S Hradetzky Uta U Krusche Ursula U Wenzel Hans-Christian HC Staginnus Annegret A Schaller Jörg J Müller Valentina V Tauer Christiane C Gebhardt Matthias M Schubert Katja K Almustafa Zaid Z Stadler Rudolf R Fuchs Andrea A Sitaru Cassian C Retzlaff Carsten C Overbeck Cora C Neumann Thomas T Kerschnitzki Anette A Krause Stephan S Schaller Martin M Walker Birgit B Walther Thomas T Köhler Lars L Albrecht Manuela M Willing Ursula U Monod Michel M Salamin Karine K Burmester Anke A Koch Daniela D Krüger Constanze C Uhrlaß Silke S

Journal of fungi (Basel, Switzerland) 20201005 4

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 ...[more]

PMID: 33027904

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Project description:Trichophyton (T.) mentagrophytes ITS genotype VIII, also known as Trichophyton indotineae, is a new species of the T. mentagrophytes/T. interdigitale complex and its first records, albeit under a different species name, are from the Indian subcontinent, Middle Eastern Asia, and West Asia. T. mentagrophytes genotype VIII (T. indotineae) has spread globally and has now been documented in over 30 countries. The aim of this study was to investigate the occurrence and proportion of terbinafine- and itraconazole-resistant isolates of T. mentagrophytes ITS genotype VIII (T. indotineae) in Bangladesh. This was part of an official collaborative project between IADVL (Indian Association of Dermatologists, Venereologists, and Leprologists) and Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. Over a period of 6 months, ninety-nine patients of chronic recalcitrant tinea corporis were recruited from BSMMU hospital. Species identification was performed by fungal culture and morphological observation of the upper and lower surfaces of fungal colonies, as well as by using fluorescent microscopy. In addition, a PCR (polymerase chain reaction)-ELISA was performed to group the patients into those with the T. mentagrophytes/T. interdigitale complex. The internal transcribed spacer (ITS) gene was sequenced. Samples were tested for resistance to terbinafine and itraconazole by mutational analyses of the squalene epoxidase (SQLE) and the ergosterol 11B (ERG11B) genes. A total of 79/99 samples showed a positive culture. In 76 of these isolates, T. mentagrophytes ITS genotype VIII (T. indotineae) could be reliably identified both by culture and molecular testing. Resistance testing revealed terbinafine resistance in 49 and itraconazole resistance in 21 patients. Among these, 11 patients were resistant to both the antifungal agents. Mutations L393S, L393F, F397L, and F397I of the SQLE gene were associated with terbinafine resistance. Resistance to itraconazole could not be explained by mutations in the ERG11B gene. Infections with T. mentagrophytes ITS genotype VIII (T. indotineae) have become a public health issue with potentially global ramifications. About 62% of samples from Bangladesh showed resistance to terbinafine, making oral itraconazole the most effective drug currently available, although resistance to itraconazole and both terbinafine and itraconazole also exists.

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

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

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