In Vitro and In Vivo Activity of Oxazolidinone Candidate OTB-658 against Mycobacterium tuberculosis

Shaochen Guo; Bin Wang; Lei FuXi ChenWeiyan ZhangHaihong HuangYu Lu

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In Vitro and In Vivo Activity of Oxazolidinone Candidate OTB-658 against Mycobacterium tuberculosis

机译：In Vitro and In Vivo Activity of Oxazolidinone Candidate OTB-658 against Mycobacterium tuberculosis

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In this work, we assess antituberculosis activity of OTB-658 in vitro and in vivo. In vitro, OTB-658 showed bacteriostatic effectiveness with a lower MIC than line-zolid against Mycobacterium tuberculosis. The minimal bactericidal concentrations and time-kill curves for OTB-658 indicated inhibition activity similar to that of linezolid. OTB-658 entered macrophages to inhibit M. tuberculosis growth. OTB-658 had a low mutation frequency (10~(-8)), which would prevent drug-resistant mutations from emerging in combination regimens. In vivo, OTB-658 reduced CFU counts in the lungs and slightly inhibited bacterial growth in the spleen in the early stage and steady state in acute and chronic murine TB models. These results support the preclinical evaluation of OTB-658 and further clinical trials in China.

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来源
《Antimicrobial agents and chemotherapy.》 |2021年第11期|e00974-e1021|共48页
作者
Shaochen Guo; Bin Wang; Lei FuXi ChenWeiyan ZhangHaihong HuangYu Lu;
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作者单位

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology;

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原文格式 PDF
正文语种英语
中图分类治疗学;
关键词
Mycobacterium tuberculosis; OTB-658; antituberculosis activity; oxazolidinone;

In Vitro and In Vivo Activity of Oxazolidinone Candidate OTB-658 against Mycobacterium tuberculosis

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