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Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination

In this retrospective study in China, we aimed to: (1) determine the prevalence of linezolid (LZD) resistance among multidrug-resistant tuberculosis (MDR-TB)-infected patients; (2) monitor for dynamic LZD susceptibility changes during anti-TB treatment; and (3) explore molecular mechanisms conferrin...

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Autores principales: Du, Jian, Gao, Jingtao, Yu, Yanhong, Li, Qingfeng, Bai, Guanghong, Shu, Wei, Gao, Mengqiu, Liu, Yuhong, Wang, Lu, Wang, Yufeng, Xue, Zhongtan, Huo, Fengmin, Li, Liang, Pang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126624/
https://www.ncbi.nlm.nih.gov/pubmed/34012425
http://dx.doi.org/10.3389/fmicb.2021.655653
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author Du, Jian
Gao, Jingtao
Yu, Yanhong
Li, Qingfeng
Bai, Guanghong
Shu, Wei
Gao, Mengqiu
Liu, Yuhong
Wang, Lu
Wang, Yufeng
Xue, Zhongtan
Huo, Fengmin
Li, Liang
Pang, Yu
author_facet Du, Jian
Gao, Jingtao
Yu, Yanhong
Li, Qingfeng
Bai, Guanghong
Shu, Wei
Gao, Mengqiu
Liu, Yuhong
Wang, Lu
Wang, Yufeng
Xue, Zhongtan
Huo, Fengmin
Li, Liang
Pang, Yu
author_sort Du, Jian
collection PubMed
description In this retrospective study in China, we aimed to: (1) determine the prevalence of linezolid (LZD) resistance among multidrug-resistant tuberculosis (MDR-TB)-infected patients; (2) monitor for dynamic LZD susceptibility changes during anti-TB treatment; and (3) explore molecular mechanisms conferring LZD resistance. A total of 277 MDR-TB patients receiving bedaquiline (BDQ)-containing regimens in 13 TB specialized hospitals across China were enrolled in the study. LZD and BDQ susceptibility rates were determined using the minimum inhibitory concentration (MIC) method, then DNA sequences of patient isolates were analyzed using Sanger sequencing to detect mutations conferring LZD resistance. Of 277 patients in our cohort, 115 (115/277, 41.5%) with prior LZD exposure yielded 19 (19/277, 6.9%) isolates exhibiting LZD resistance. The LZD resistance rate of LZD-exposed group isolates significantly exceeded the corresponding rate for non-exposed group isolates (P = 0.047). Genetic mutations were observed in 10 (52.6%, 10/19) LZD-resistant isolates, of which a Cys154Arg (36.8%, 7/19) substitution within ribosomal protein L3 was most prevalent. Analysis of sequential positive cultures obtained from 81 LZD-treated patients indicated that cultured organisms obtained from most patients (85.2%, 69/81) retained original LZD MIC values; however, organisms cultured later from two patients exhibited significantly increased MIC values that were attributed to the rplC substitution T460C. Overall, LZD resistance was detected in 6.9% of patients of an MDR-TB cohort in China. Low rate of acquired LZD resistance was noted in MDR-TB treated with BDQ-LZD combination.
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spelling pubmed-81266242021-05-18 Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination Du, Jian Gao, Jingtao Yu, Yanhong Li, Qingfeng Bai, Guanghong Shu, Wei Gao, Mengqiu Liu, Yuhong Wang, Lu Wang, Yufeng Xue, Zhongtan Huo, Fengmin Li, Liang Pang, Yu Front Microbiol Microbiology In this retrospective study in China, we aimed to: (1) determine the prevalence of linezolid (LZD) resistance among multidrug-resistant tuberculosis (MDR-TB)-infected patients; (2) monitor for dynamic LZD susceptibility changes during anti-TB treatment; and (3) explore molecular mechanisms conferring LZD resistance. A total of 277 MDR-TB patients receiving bedaquiline (BDQ)-containing regimens in 13 TB specialized hospitals across China were enrolled in the study. LZD and BDQ susceptibility rates were determined using the minimum inhibitory concentration (MIC) method, then DNA sequences of patient isolates were analyzed using Sanger sequencing to detect mutations conferring LZD resistance. Of 277 patients in our cohort, 115 (115/277, 41.5%) with prior LZD exposure yielded 19 (19/277, 6.9%) isolates exhibiting LZD resistance. The LZD resistance rate of LZD-exposed group isolates significantly exceeded the corresponding rate for non-exposed group isolates (P = 0.047). Genetic mutations were observed in 10 (52.6%, 10/19) LZD-resistant isolates, of which a Cys154Arg (36.8%, 7/19) substitution within ribosomal protein L3 was most prevalent. Analysis of sequential positive cultures obtained from 81 LZD-treated patients indicated that cultured organisms obtained from most patients (85.2%, 69/81) retained original LZD MIC values; however, organisms cultured later from two patients exhibited significantly increased MIC values that were attributed to the rplC substitution T460C. Overall, LZD resistance was detected in 6.9% of patients of an MDR-TB cohort in China. Low rate of acquired LZD resistance was noted in MDR-TB treated with BDQ-LZD combination. Frontiers Media S.A. 2021-05-03 /pmc/articles/PMC8126624/ /pubmed/34012425 http://dx.doi.org/10.3389/fmicb.2021.655653 Text en Copyright © 2021 Du, Gao, Yu, Li, Bai, Shu, Gao, Liu, Wang, Wang, Xue, Huo, Li and Pang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Du, Jian
Gao, Jingtao
Yu, Yanhong
Li, Qingfeng
Bai, Guanghong
Shu, Wei
Gao, Mengqiu
Liu, Yuhong
Wang, Lu
Wang, Yufeng
Xue, Zhongtan
Huo, Fengmin
Li, Liang
Pang, Yu
Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination
title Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination
title_full Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination
title_fullStr Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination
title_full_unstemmed Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination
title_short Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination
title_sort low rate of acquired linezolid resistance in multidrug-resistant tuberculosis treated with bedaquiline-linezolid combination
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126624/
https://www.ncbi.nlm.nih.gov/pubmed/34012425
http://dx.doi.org/10.3389/fmicb.2021.655653
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