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Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition

OBJECTIVES: Recently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive and retrospective study to determine the prevalence of XDR-TB in a Chinese multidrug-resistant TB (MDR-TB) cohort. METHODS: Broth microdilution method was perfor...

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Autores principales: Yao, Cong, Guo, Haiping, Li, Qiang, Zhang, Xuxia, Shang, Yuanyuan, Li, Tongxin, Wang, Yufeng, Xue, Zhongtan, Wang, Lu, Li, Liang, Pang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393791/
https://www.ncbi.nlm.nih.gov/pubmed/34446095
http://dx.doi.org/10.1186/s13756-021-00995-8
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author Yao, Cong
Guo, Haiping
Li, Qiang
Zhang, Xuxia
Shang, Yuanyuan
Li, Tongxin
Wang, Yufeng
Xue, Zhongtan
Wang, Lu
Li, Liang
Pang, Yu
author_facet Yao, Cong
Guo, Haiping
Li, Qiang
Zhang, Xuxia
Shang, Yuanyuan
Li, Tongxin
Wang, Yufeng
Xue, Zhongtan
Wang, Lu
Li, Liang
Pang, Yu
author_sort Yao, Cong
collection PubMed
description OBJECTIVES: Recently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive and retrospective study to determine the prevalence of XDR-TB in a Chinese multidrug-resistant TB (MDR-TB) cohort. METHODS: Broth microdilution method was performed to determine in vitro susceptibilities of Mycobacterium tuberculosis (MTB) isolates to (FQs), bedaquiline (BDQ) and linezolid (LZD). The putative drug target genes conferring drug resistance were screened by DNA sequencing. RESULTS: A total of 425 MDR-TB isolates were included from 13 pilots in China. LZD and BDQ resistance were noted in 30 (7.1%) and 10 (2.4%) isolates. On the basis of latest definitions, 114 (26.8%) were MDR-TB, 282 (66.4%) were pre-XDR-TB, and 29 (6.8%) were XDR-TB. Among 311 FQ-resistant isolates, 265 harbored genetic mutations within QRDRs. The most common mutations were observed at codon 94 of gyrA, accounting for 47.2% of FQ-resistant MTB isolates. Only mutations within the Rv0678 gene were found to confer BDQ resistance in our cohort, conferring 40.0% of BDQ resistance. For LZD resistance, 53.3% of LZD-resistant isolates carried genetic mutations in rplC or 23S rRNA. The most frequent mutation was Cys154Arg in the rplC gene. In addition, we recorded two MDR-TB patients with resistance to both BDQ and LZD, of which one patient experienced continuous positive culture of MTB despite inclusion of efficacious moxifloxacin. CONCLUSION: Our results demonstrate that the low prevalence of XDR-TB holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination, whereas the high prevalence of FQ-resistance in MDR-TB patients warrants national attention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13756-021-00995-8.
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spelling pubmed-83937912021-08-30 Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition Yao, Cong Guo, Haiping Li, Qiang Zhang, Xuxia Shang, Yuanyuan Li, Tongxin Wang, Yufeng Xue, Zhongtan Wang, Lu Li, Liang Pang, Yu Antimicrob Resist Infect Control Research OBJECTIVES: Recently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive and retrospective study to determine the prevalence of XDR-TB in a Chinese multidrug-resistant TB (MDR-TB) cohort. METHODS: Broth microdilution method was performed to determine in vitro susceptibilities of Mycobacterium tuberculosis (MTB) isolates to (FQs), bedaquiline (BDQ) and linezolid (LZD). The putative drug target genes conferring drug resistance were screened by DNA sequencing. RESULTS: A total of 425 MDR-TB isolates were included from 13 pilots in China. LZD and BDQ resistance were noted in 30 (7.1%) and 10 (2.4%) isolates. On the basis of latest definitions, 114 (26.8%) were MDR-TB, 282 (66.4%) were pre-XDR-TB, and 29 (6.8%) were XDR-TB. Among 311 FQ-resistant isolates, 265 harbored genetic mutations within QRDRs. The most common mutations were observed at codon 94 of gyrA, accounting for 47.2% of FQ-resistant MTB isolates. Only mutations within the Rv0678 gene were found to confer BDQ resistance in our cohort, conferring 40.0% of BDQ resistance. For LZD resistance, 53.3% of LZD-resistant isolates carried genetic mutations in rplC or 23S rRNA. The most frequent mutation was Cys154Arg in the rplC gene. In addition, we recorded two MDR-TB patients with resistance to both BDQ and LZD, of which one patient experienced continuous positive culture of MTB despite inclusion of efficacious moxifloxacin. CONCLUSION: Our results demonstrate that the low prevalence of XDR-TB holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination, whereas the high prevalence of FQ-resistance in MDR-TB patients warrants national attention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13756-021-00995-8. BioMed Central 2021-08-26 /pmc/articles/PMC8393791/ /pubmed/34446095 http://dx.doi.org/10.1186/s13756-021-00995-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yao, Cong
Guo, Haiping
Li, Qiang
Zhang, Xuxia
Shang, Yuanyuan
Li, Tongxin
Wang, Yufeng
Xue, Zhongtan
Wang, Lu
Li, Liang
Pang, Yu
Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition
title Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition
title_full Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition
title_fullStr Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition
title_full_unstemmed Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition
title_short Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition
title_sort prevalence of extensively drug-resistant tuberculosis in a chinese multidrug-resistant tb cohort after redefinition
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393791/
https://www.ncbi.nlm.nih.gov/pubmed/34446095
http://dx.doi.org/10.1186/s13756-021-00995-8
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