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The Domestic Isolation of Terbinafine- and Itraconazole-Resistant Trichophyton indotineae in Chinese Mainland

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A Correction to this article was published on 02 November 2023

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Abstract

Background

Trichophyton indotineae, a new species of dermatophytes, has become a significant concern in treating dermatophytosis due to the high level of terbinafine resistance reported in India and even worldwide.

Objectives

This study aimed to report the terbinafine- and itraconazole-resistant T. indotineae in Chinese mainland, by identifying the phylogenetic classification of the isolate strain, and detecting the drug resistance, gene mutation and expression.

Patients/Methods

The skin scales of the patient were cultured on SDA and the isolate was authenticated by DNA sequencing and MALDI-TOF MS. Antifungal susceptibility testing was performed following the M38-A2 CLSI protocol to examine the MICs values of terbinafine, itraconazole, fluconazole, etc. The strain was screened for mutations in the squalene epoxidase (SQLE) gene by Sanger sequencing and detected the expression of CYP51A and CYP51B by qRT-PCR.

Results

A multi-resistant ITS genotype VIII sibling of the T. mentagrophytes complex (T. indotineae) was isolated in Chinese mainland. The strain harbored high terbinafine MIC of > 32 μg/mL and itraconazole MIC of 1.0 μg/mL, which was identified a mutation in the squalene epoxidase gene with amino acid substitution (Phe397Leu, mutation 1191C > A). In addition, overexpression of CYP51A and CYP51B was observed. With multiple relapses, the patient finally achieved clinical cure by itraconazole pulse therapy and topical clotrimazole cream for 5 weeks.

Conclusions

The first domestic strain of terbinafine- and itraconazole-resistant T. indotineae from a patient in Chinese mainland was isolated. Itraconazole pulse therapy can be an effective method for the treatment of T. indotineae.

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Acknowledgements

This research has been supported by the National Key Research and Development Program of China (2022YFC2504804, 2022YFC2504800), Double-Innovation Doctor Program of Jiangsu province (Grant Number JSSCBS20221924), CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-039), National Science and Technology Infrastructure of China (National Pathogen Resource, Center NPRC-32), the basic scientific research fund projects of Chinese Academy of Medical Sciences (2021-PT310-006), National Natural Science Foundation of China (Grant Number 81972949).

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Author notes

  1. Xue Kong and Ge Song have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Mycology, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China

    Xue Kong, Huan Mei, Hailin Zheng, Xiaofang Li, Xiaodong She, Weida Liu & Guanzhao Liang

  2. Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China

    Ge Song

  3. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, 210042, China

    Xue Kong, Xiaofang Li, Xiaodong She, Weida Liu & Guanzhao Liang

  4. Center of Expertise in Mycology, Radboud University Medical Center, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

    Chao Tang & Sybren de Hoog

  5. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 21166, China

    Weida Liu

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Contributions

This patient was admitted, treated and followed up by GL. The study was conceived by GL and WL. XK and GL analyzed and interpreted of the data; HZ and MH involved in experiment preparation, fungus identification, antifungal susceptibility testing. XK, GL and GS drafted the manuscript, GS and CT revised it critically for important intellectual content. WL, XS and XL provided funds and experiment support. We thank SX and Zybio Company (Chong Qing, China) for performing the MALDI-tree.

Corresponding authors

Correspondence to Weida Liu or Guanzhao Liang.

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Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

The studies involving human participants were reviewed and approved by 2022-KY-037. The patient has written the informed consent in this study.

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Handling Editor: Rui Kano.

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The original online version of this article was revised: In Result section under sub-heading “Patient”, the sentence “The lesions were disappeared completely after three weeks of treatment of itraconazole therapy (0.2 g/twice a day) and naftifine hydrochloride & ketoconazole cream, but the rash recurred after two weeks of drug withdrawal” is included. The caption of table 1 and 2 is swapped correctly. The MIC of posaconazole is added at the last column of Table 2. In the last column of table 1, the citations in the last four rows are corrected from [22] to [20].

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Kong, X., Song, G., Mei, H. et al. The Domestic Isolation of Terbinafine- and Itraconazole-Resistant Trichophyton indotineae in Chinese Mainland. Mycopathologia 188, 383–393 (2023). https://doi.org/10.1007/s11046-023-00761-x

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