Andreas Ebert1,2, Michel Monod3, Karine Salamin3, Anke Burmester4, Silke Uhrlaß2, Cornelia Wiegand4, Uta-Christina Hipler4, Constanze Krüger2, Daniela Koch2, Franziska Wittig2, Shyam B Verma5, Archana Singal6, Sanjeev Gupta7, Resham Vasani8, Abir Saraswat9, Rengarajan Madhu10, Saumya Panda11, Anupam Das11, Mahendra M Kura12, Akshy Kumar13, Shital Poojary14, Sibylle Schirm15, Yvonne Gräser16, Uwe Paasch17, Pietro Nenoff2. 1. Medizinische Fakultät, Universität Leipzig, Leipzig, Germany. 2. Labor für medizinische Mikrobiologie, Rötha, Germany. 3. Service de Dermatologie et Vénéréologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 4. Klinik für Hautkrankheiten, Universitätsklinikum Jena, Jena, Germany. 5. Nirvan" and "In Skin" Clinics, Vadodara, India. 6. Department of Dermatology and STD, University College of Medical Sciences and GTB Hospital, Delhi, India. 7. M M Institute of Medical Sciences and Research, MM Deemed to be University, Ambala, India. 8. Department of Dermatology, Bhojani Clinic, Mumbai, India. 9. Department of Dermatology, Indushree Skin Clinic, Lucknow, India. 10. Department of Dermatology (Mycology), Madras Medical College, Chennai, India. 11. Department of Dermatology, KPC Medical College, Kolkata, India. 12. Department of Dermatology, Grant Medical College & Sir J J Group of Hospitals, Mumbai, India. 13. Department of Dermatology, Government Medical College, Kota, India. 14. Department of Dermatology, K J Somaiya Medical College, Mumbai, India. 15. Institut für Medizinische Informatik, Statistik und Epidemiologie, Leipzig, Germany. 16. Institut für Mikrobiologie und Hygiene, Nationales Konsiliarlabor für Dermatophyten, Universitätsmedizin Berlin Charité, Berlin, Germany. 17. Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Leipzig, Leipzig, Germany.
Abstract
BACKGROUND: An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. OBJECTIVES: The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene. PATIENTS/ METHODS: We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE. RESULTS: Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole. CONCLUSIONS: The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.
BACKGROUND: An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. OBJECTIVES: The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene. PATIENTS/ METHODS: We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE. RESULTS:Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole. CONCLUSIONS: The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.
Authors: Aditya K Gupta; Helen J Renaud; Emma M Quinlan; Neil H Shear; Vincent Piguet Journal: Am J Clin Dermatol Date: 2020-12-22 Impact factor: 7.403
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Authors: Xue Kong; Chao Tang; Ashutosh Singh; Sarah A Ahmed; Abdullah M S Al-Hatmi; Anuradha Chowdhary; Pietro Nenoff; Yvonne Gräser; Steven Hainsworth; Ping Zhan; Jacques F Meis; Paul E Verweij; Weida Liu; G Sybren de Hoog Journal: Antimicrob Agents Chemother Date: 2021-07-16 Impact factor: 5.191