In vitro activity of radezolid against Enterococcus faecium and compared with linezolid

Abstract

This study aims to explore the antimicrobial activity and resistance mechanism of radezolid against Enterococcus faecium, and to compare it with linezolid. A total of 232 E. faecium isolates were collected, and the minimal inhibitory concentrations of radezolid and linezolid were determined. The radezolid- or linezolid-nonsusceptible isolates were selected by passage in vitro under antibiotic pressure. Oxazolidinone-resistant chromosomal genes and plasmid-borne genes cfr, optrA, and poxtA were detected by PCR and sequenced. Radezolid MIC90 was 4 times lower than linezolid in the 232 E. faecium isolates, including the linezolid-nonsusceptible isolates. This study found that 6.5% (15/232) of the E. faecium isolates carried the plasmid-borne genes cfr and 9.5% (22/232) carried the optrA gene, but only one of these isolates had a linezolid MIC ≥ 4 mg l−1. Among the 13 isolates with linezolid MIC ≥ 4 mg l−1 or radezolid MIC ≥ 1 mg l−1, genetic mutations in the V domain of 23S rRNA were only found in four isolates. The MICs of linezolid or radezolid against three E. faecium isolates increased to 4–16 times of the initial MICs after 140 days of daily passage in drug-containing medium. The radezolid MICs remained 8–16 times lower than linezolid in those linezolid-induced resistant isolates. Conversely, the radezolid MICs increased while the linezolid MICs remained unchanged in the most of the radezolid-induced resistant isolates. Radezolid exhibits excellent antimicrobial activity against E. faecium, and has minimal cross resistance with linezolid.

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Funding

This work was supported by the following grants: the National Natural Science Foundation of China (No. 81170370 and No. 81601797); the Sanming Project of Medicine in Shenzhen (grant number SMGC201705029); Science, Technology and Innovation Commission of Shenzhen Municipality of key funds (JCYJ20180508162403996; JCYJ20170412143551332) and basic research funds (JCYJ20180302144721183; JCYJ20180302144340004;JCYJ20180302144345028; JCYJ20180302144431923).

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ZX carried out the PCR experiments, MLST and CC analysis, interpreted the sequenced data, and drafted the manuscript. YW participated in the collection of E. faecium isolates, isolates identified and MIC test. YW participated in the induction of linezolid and radezolid-resistance test, MLST and CC analysis. GX, HC, and JC participated in the collection of E. faecium isolates, MIC test, induction of linezolid and radezolid-resistance test, PCR experiments and interpreted the sequenced data. ZY participated in the MLST and CC analysis, and reviewed this manuscript. ZC and JZ designed the study, conducted the data analysis, and provided critical revisions of the manuscript for valuable intellectual content.

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Correspondence to Zhong Chen or Jinxin Zheng.

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The authors declare that they have no conflict of interest.

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All procedures involving human subjects were approved by the institutional ethical committee of Shenzhen Nanshan People’s Hospital and the fourth Affiliated Hospital of Harbin Medical University. Isolates were collected as part of the routine clinical management of patients, according to the national guidelines in China. Therefore, informed consent was not sought.

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Xu, Z., Wei, Y., Wang, Y. et al. In vitro activity of radezolid against Enterococcus faecium and compared with linezolid. J Antibiot (2020). https://doi.org/10.1038/s41429-020-0345-y

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