Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China

Background: The natural resistance of rapidly growing mycobacteria (RGM) to multiple antibiotics renders the treatment of the infections caused less successful. The objective of this study was to evaluate the in vitro susceptibilities of four oxazolidinones against different RGM species. Methods: Th...

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Main Authors: Shu’an Wen, Xiaopan Gao, Weijie Zhao, Fengmin Huo, Guanglu Jiang, Lingling Dong, Liping Zhao, Fen Wang, Xia Yu, Hairong Huang
Format: Article
Language:English
Published: Elsevier 2021-08-01
Series:International Journal of Infectious Diseases
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971221005440
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author Shu’an Wen
Xiaopan Gao
Weijie Zhao
Fengmin Huo
Guanglu Jiang
Lingling Dong
Liping Zhao
Fen Wang
Xia Yu
Hairong Huang
author_facet Shu’an Wen
Xiaopan Gao
Weijie Zhao
Fengmin Huo
Guanglu Jiang
Lingling Dong
Liping Zhao
Fen Wang
Xia Yu
Hairong Huang
author_sort Shu’an Wen
collection DOAJ
description Background: The natural resistance of rapidly growing mycobacteria (RGM) to multiple antibiotics renders the treatment of the infections caused less successful. The objective of this study was to evaluate the in vitro susceptibilities of four oxazolidinones against different RGM species. Methods: The microplate alamarBlue assay was performed to identify the minimum inhibitory concentrations (MICs) of four oxazolidinones – delpazolid, sutezolid, tedizolid, and linezolid – for 32 reference strains and 115 clinical strains of different RGM species. The MIC breakpoint concentration was defined as 16 μg/ml for linezolid. Next, the gene fragments associated with oxazolidinone resistance were amplified and sequenced, and mutations were defined in contrast with the sequences of the reference strains. Results: Tedizolid showed the strongest inhibitory activity against the Mycobacterium abscessus isolates. Delpazolid exhibited better antimicrobial activity against the Mycobacterium fortuitum isolates when compared to linezolid, with 4-fold lower MIC values. The protein alignment and structure-based analysis showed that there might be no correlation between oxazolidinone resistance and mutations in the rplC, rplD, and 23S rRNA genes in the tested RGM. Conclusions: Tedizolid had the strongest inhibitory activity against M. abscessus in vitro, while delpazolid presented the best inhibitory activity against M. fortuitum. This provides important insights into the potential clinical application of oxazolidinones to treat RGM infections.
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spelling doaj.art-a7739fd05d2b49dd820d9559815bf4002022-12-21T18:34:03ZengElsevierInternational Journal of Infectious Diseases1201-97122021-08-01109253260Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, ChinaShu’an Wen0Xiaopan Gao1Weijie Zhao2Fengmin Huo3Guanglu Jiang4Lingling Dong5Liping Zhao6Fen Wang7Xia Yu8Hairong Huang9National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaMOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaThe Administration Office of Clinical Trial, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, China; Corresponding authors: Hairong Huang and Xia Yu, National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beiguan St, No. 9, Tongzhou Qu, Beijing 101149, China.National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, China; Corresponding authors: Hairong Huang and Xia Yu, National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beiguan St, No. 9, Tongzhou Qu, Beijing 101149, China.Background: The natural resistance of rapidly growing mycobacteria (RGM) to multiple antibiotics renders the treatment of the infections caused less successful. The objective of this study was to evaluate the in vitro susceptibilities of four oxazolidinones against different RGM species. Methods: The microplate alamarBlue assay was performed to identify the minimum inhibitory concentrations (MICs) of four oxazolidinones – delpazolid, sutezolid, tedizolid, and linezolid – for 32 reference strains and 115 clinical strains of different RGM species. The MIC breakpoint concentration was defined as 16 μg/ml for linezolid. Next, the gene fragments associated with oxazolidinone resistance were amplified and sequenced, and mutations were defined in contrast with the sequences of the reference strains. Results: Tedizolid showed the strongest inhibitory activity against the Mycobacterium abscessus isolates. Delpazolid exhibited better antimicrobial activity against the Mycobacterium fortuitum isolates when compared to linezolid, with 4-fold lower MIC values. The protein alignment and structure-based analysis showed that there might be no correlation between oxazolidinone resistance and mutations in the rplC, rplD, and 23S rRNA genes in the tested RGM. Conclusions: Tedizolid had the strongest inhibitory activity against M. abscessus in vitro, while delpazolid presented the best inhibitory activity against M. fortuitum. This provides important insights into the potential clinical application of oxazolidinones to treat RGM infections.http://www.sciencedirect.com/science/article/pii/S1201971221005440Rapidly growing mycobacteriaDelpazolidSutezolidTedizolidLinezolidAntimicrobial activity
spellingShingle Shu’an Wen
Xiaopan Gao
Weijie Zhao
Fengmin Huo
Guanglu Jiang
Lingling Dong
Liping Zhao
Fen Wang
Xia Yu
Hairong Huang
Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China
International Journal of Infectious Diseases
Rapidly growing mycobacteria
Delpazolid
Sutezolid
Tedizolid
Linezolid
Antimicrobial activity
title Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China
title_full Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China
title_fullStr Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China
title_full_unstemmed Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China
title_short Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China
title_sort comparison of the in vitro activity of linezolid tedizolid sutezolid and delpazolid against rapidly growing mycobacteria isolated in beijing china
topic Rapidly growing mycobacteria
Delpazolid
Sutezolid
Tedizolid
Linezolid
Antimicrobial activity
url http://www.sciencedirect.com/science/article/pii/S1201971221005440
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