National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, China.
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Int J Infect Dis. 2021 Aug;109:253-260. doi: 10.1016/j.ijid.2021.06.055. Epub 2021 Jul 1.
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.
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.
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.
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.
快速生长分枝杆菌（RGM）对多种抗生素的天然耐药性使得感染的治疗成功率降低。本研究的目的是评估四种恶唑烷酮类药物对不同 RGM 种的体外药敏活性。
采用微量肉汤 alamarBlue 法测定四种恶唑烷酮类药物——delpazolid、sutezolid、tedizolid 和 linezolid 对 32 株参考菌株和 115 株不同 RGM 种临床分离株的最小抑菌浓度（MIC）。linezolid 的 MIC 折点浓度定义为 16μg/ml。然后，扩增并测序与恶唑烷酮类药物耐药相关的基因片段，并与参考菌株的序列进行比较，确定突变。
tedizolid 对脓肿分枝杆菌分离株的抑制活性最强。与 linezolid 相比，delpazolid 对偶然分枝杆菌分离株的抗菌活性更好，MIC 值低 4 倍。蛋白比对和基于结构的分析表明，在测试的 RGM 中，恶唑烷酮类药物耐药性与 rplC、rplD 和 23S rRNA 基因的突变之间可能没有相关性。
tedizolid 对体外脓肿分枝杆菌的抑制活性最强，而 delpazolid 对偶然分枝杆菌的抑制活性最好。这为恶唑烷酮类药物治疗 RGM 感染的临床应用提供了重要的见解。
