Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study

被引：191

作者：

Ebert, Andreas ^{[1
,2
]}

Monod, Michel ^{[3
]}

Salamin, Karine ^{[3
]}

Burmester, Anke ^{[4
]}

Uhrlass, Silke ^{[2
]}

Wiegand, Cornelia ^{[4
]}

Hipler, Uta-Christina ^{[4
]}

Krueger, Constanze ^{[2
]}

Koch, Daniela ^{[2
]}

Wittig, Franziska ^{[2
]}

Verma, Shyam B. ^{[5
]}

Singal, Archana ^{[6
,7
]}

Gupta, Sanjeev ^{[8
]}

Vasani, Resham ^{[9
]}

Saraswat, Abir ^{[10
]}

Madhu, Rengarajan ^{[11
]}

Panda, Saumya ^{[12
]}

Das, Anupam ^{[12
]}

Kura, Mahendra M. ^{[13
,14
]}

Kumar, Akshy ^{[15
]}

Poojary, Shital ^{[16
]}

Schirm, Sibylle ^{[17
]}

Graeser, Yvonne ^{[18
]}

Paasch, Uwe ^{[19
]}

Nenoff, Pietro ^{[2
]}

机构：

[1] Univ Leipzig, Med Fak, Leipzig, Germany

[2] Lab Med Mikrobiol, Rotha, Germany

[3] CHU Vaudois, Serv Dermatol & Venereol, Lausanne, Switzerland

[4] Univ Klinikum Jena, Klin Hautkrankheiten, Jena, Germany

[5] Nirvan & In Skin Clin, Vadodara, India

[6] Univ Coll Med Sci, Dept Dermatol & STD, Delhi, India

[7] GTB Hosp, Delhi, India

[8] MM Deemed Univ, MM Inst Med Sci & Res, Ambala, India

[9] Bhojani Clin, Dept Dermatol, Mumbai, Maharashtra, India

[10] Indushree Skin Clin, Dept Dermatol, Lucknow, Uttar Pradesh, India

[11] Madras Med Coll & Govt Gen Hosp, Dept Dermatol Mycol, Chennai, Tamil Nadu, India

[12] KPC Med Coll, Dept Dermatol, Kolkata, India

[13] Grant Med Coll, Dept Dermatol, Mumbai, Maharashtra, India

[14] Sir JJ Grp Hosp, Mumbai, Maharashtra, India

[15] Govt Med Coll, Dept Dermatol, Kota, India

[16] KJ Somaiya Med Coll, Dept Dermatol, Mumbai, Maharashtra, India

[17] Inst Med Informat Stat & Epidemiol, Leipzig, Germany

[18] Univ Med Berlin Charite, Natl Konsiliarlab Dermatophyten, Inst Mikrobiol & Hyg, Berlin, Germany

[19] Univ Klinikum Leipzig, Klin & Poliklin Dermatol Venerol & Allergol, Leipzig, Germany

来源：

MYCOSES | 2020年 / 63卷 / 07期

关键词：

epidemiology; infectious diseases; mechanisms of resistance; molecular typing; public health; tinea; IN-VITRO; SUSCEPTIBILITY; MENTAGROPHYTES; TERBINAFINE; INFECTIONS; MUTATIONS; DRUGS; GENE;

D O I：

10.1111/myc.13091

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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.

引用

页码：717 / 728

页数：12

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