Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study.
- Ebert A Medizinische Fakultät, Universität Leipzig, Leipzig, Germany.
- Monod M Service de Dermatologie et Vénéréologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Salamin K Service de Dermatologie et Vénéréologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Burmester A Klinik für Hautkrankheiten, Universitätsklinikum Jena, Jena, Germany.
- Uhrlaß S Labor für medizinische Mikrobiologie, Rötha, Germany.
- Wiegand C Klinik für Hautkrankheiten, Universitätsklinikum Jena, Jena, Germany.
- Hipler UC Klinik für Hautkrankheiten, Universitätsklinikum Jena, Jena, Germany.
- Krüger C Labor für medizinische Mikrobiologie, Rötha, Germany.
- Koch D Labor für medizinische Mikrobiologie, Rötha, Germany.
- Wittig F Labor für medizinische Mikrobiologie, Rötha, Germany.
- Verma SB Nirvan" and "In Skin" Clinics, Vadodara, India.
- Singal A Department of Dermatology and STD, University College of Medical Sciences and GTB Hospital, Delhi, India.
- Gupta S M M Institute of Medical Sciences and Research, MM Deemed to be University, Ambala, India.
- Vasani R Department of Dermatology, Bhojani Clinic, Mumbai, India.
- Saraswat A Department of Dermatology, Indushree Skin Clinic, Lucknow, India.
- Madhu R Department of Dermatology (Mycology), Madras Medical College, Chennai, India.
- Panda S Department of Dermatology, KPC Medical College, Kolkata, India.
- Das A Department of Dermatology, KPC Medical College, Kolkata, India.
- Kura MM Department of Dermatology, Grant Medical College & Sir J J Group of Hospitals, Mumbai, India.
- Kumar A Department of Dermatology, Government Medical College, Kota, India.
- Poojary S Department of Dermatology, K J Somaiya Medical College, Mumbai, India.
- Schirm S Institut für Medizinische Informatik, Statistik und Epidemiologie, Leipzig, Germany.
- Gräser Y Institut für Mikrobiologie und Hygiene, Nationales Konsiliarlabor für Dermatophyten, Universitätsmedizin Berlin Charité, Berlin, Germany.
- Paasch U Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Leipzig, Leipzig, Germany.
- Nenoff P Labor für medizinische Mikrobiologie, Rötha, Germany.
- 2020-04-18
Published in:
- Mycoses. - 2020
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1111/myc.13091
- PMID 32301159
- Persistent URL
- https://sonar.ch/global/documents/46318
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