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bioRxiv · 10.1101/2020.06.25.172742

In Vitro efficacy comparison of linezolid, tedizolid, sutezolid and delpazolid against rapid growing Mycobacteria isolated in Beijing, China

Wen, S.·Gao, X.·Zhao, W.·Huo, F.·Jiang, G.·Dong, L.·Zhao, L.·Wang, F.·Yu, X.·Huang, H.
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Abstract

The natural resistance of rapid growth Mycobacterium (RGM) against multiple antibiotics renders the treatment of caused infections less successful and time consuming. Therefore, new effective agents are urgently needed. The aim of this study was to evaluate the in vitro susceptibility of 115 isolates, constituting different RGM species, against four oxazolidinones i.e. delpazolid, sutezolid, tedizolid and linezolid. Additionally, 32 reference strains of different RGM species were also tested. The four oxazolidinones exhibited potent in vitro activity against the recruited RGM reference strains, 24 out of 32 RGM species had MICs [≤] 8 g/mL against all four oxazolidinones whereas tedizolid and delpazolid generally presented lower MICs than linezolid or sutezolid. Tedizolid showed the strongest activity against clinical isolates of M. abscessus with MIC50=1g/mL and MIC90=2g/mL. MIC values for tedizolid were usually 4- to 8-fold less than the MICs of linezolid for M. abscessus subsp. abscessus. The MIC distributions of sutezolid and linezolid were similar, while delpazolid showed 2-fold lower MIC as compared with linezolid. Linezolid was not active against most of the tested M. fortuitum isolates, 22 out of the 25 M. fortuitum were resistant against linezolid. However, delpazolid exhibited better antimicrobial activity against these isolates with 4-fold lower MIC values, in contrast with linezolid. In addition, the protein alignment of RplC and RplD and structure based analysis showed that there may be no correlation between oxazolidinones resistance and mutations in rplC, rplD and 23 srRNAgenes in tested RGM. This study showed tedizolid harbors the strongest inhibitory activity against M. abscessus in vitro, while delpazolid presented the best activity against M. fortuitum, which provided important insights on the potential clinical application of oxazolidinones to treat RGM infections.

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Wen, S., Gao, X., Zhao, W., Huo, F., Jiang, G., Dong, L., Zhao, L., Wang, F., Yu, X., Huang, H.. 2020-06-26. In Vitro efficacy comparison of linezolid, tedizolid, sutezolid and delpazolid against rapid growing Mycobacteria isolated in Beijing, China. https://doi.org/10.1101/2020.06.25.172742

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