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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gao W, Howden BP, Stinear TP. Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen. Curr Opin Microbiol. 2018;41:76–82.
Lebreton F, Manson AL, Saavedra JT, Straub TJ, Earl AM, Gilmore MS. Tracing the Enterococci from paleozoic origins to the hospital. Cell. 2017;169:849–61.e13.
Sadowy E. Linezolid resistance genes and genetic elements enhancing their dissemination in enterococci and streptococci. Plasmid. 2018;99:89–98.
Mercuro NJ, Davis SL, Zervos MJ, Herc ES. Combatting resistant enterococcal infections: a pharmacotherapy review. Expert Opin Pharmacother. 2018;19:979–92.
Bi R, Qin T, Fan W, Ma P, Gu B. The emerging problem of linezolid-resistant enterococci. J Glob Antimicrob Resist. 2018;13:11–9.
Yadav G, Thakuria B, Madan M, Agwan V, Pandey A. Linezolid and Vancomycin Resistant Enterococci: A Therapeutic Problem. J Clin Diagn Res. 2017;11:Gc07–11.
Pfaller MA, Mendes RE, Streit JM, Hogan PA, Flamm RK. Five-year summary of in vitro activity and resistance mechanisms of linezolid against clinically important gram-positive cocci in the United States from the LEADER Surveillance Program (2011 to 2015). Antimicrob Agents Chemother. 2017;61:e00609-17.
Janardhanan J, Chang M, Mobashery S. The oxadiazole antibacterials. Curr Opin Microbiol. 2016;33:13–7.
Karpiuk I, Tyski S. Looking for the new preparations for antibacterial therapy. V. New antimicrobial agents from the oxazolidinones groups in clinical trials. Prz Epidemiol. 2017;71:207–19.
Bai B, Hu K, Li H, Yao W, Li D, Chen Z, et al. Effect of tedizolid on clinical Enterococcus isolates: in vitro activity, distribution of virulence factor, resistance genes and multilocus sequence typing. FEMS Microbiol Lett. 2018;365:fnx284.
Pfaller MA, Flamm RK, Jones RN, Farrell DJ, Mendes RE. Activities of tedizolid and linezolid determined by the reference broth microdilution method against 3,032 gram-positive bacterial isolates collected in Asia-Pacific, Eastern Europe, and Latin American countries in 2014. Antimicrob Agents Chemother. 2016;60:5393–9.
Vehreschild M, Haverkamp M, Biehl LM, Lemmen S, Fatkenheuer G. Vancomycin-resistant enterococci (VRE): a reason to isolate? Infection. 2019;47:7–11.
Yang J, Jiang Y, Guo L, Ye L, Ma Y, Luo Y. Prevalence of diverse clones of vancomycin-resistant Enterococcus faecium ST78 in a Chinese hospital. Microbial Drug Resist. 2016;22:294–300.
Zhu X, Zheng B, Wang S, Willems RJ, Xue F, Cao X, et al. Molecular characterisation of outbreak-related strains of vancomycin-resistant Enterococcus faecium from an intensive care unit in Beijing, China. J hosp Infect. 2009;72:147–54.
Chen C, Xu X, Qu T, Yu Y, Ying C, Liu Q, et al. Prevalence of the fosfomycin-resistance determinant, fosB3, in Enterococcus faecium clinical isolates from China. J Med Microb. 2014;63:1484–9.
Kuo AJ, Su LH, Shu JC, Wang JT, Wang JH, Fung CP, et al. National surveillance on vancomycin-resistant Enterococcus faecium in Taiwan: emergence and widespread of ST414 and a Tn1546-like element with simultaneous insertion of IS1251-like and IS1678. PloS ONE. 2014;9:e115555.
Klare I, Fleige C, Geringer U, Thurmer A, Bender J, Mutters NT, et al. Increased frequency of linezolid resistance among clinical Enterococcus faecium isolates from German hospital patients. J Glob Antimicrob Resist. 2015;3:128–31.
Billal DS, Feng J, Leprohon P, Legare D, Ouellette M. Whole genome analysis of linezolid resistance in Streptococcus pneumoniae reveals resistance and compensatory mutations. BMC Genom. 2011;12:512.
Hua R, Xia Y, Wu W, Yan J, Yang M. Whole transcriptome analysis reveals potential novel mechanisms of low-level linezolid resistance in Enterococcus faecalis. Gene. 2018;647:143–9.
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).
Author information
Authors and Affiliations
Contributions
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.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
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.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Xu, Z., Wei, Y., Wang, Y. et al. In vitro activity of radezolid against Enterococcus faecium and compared with linezolid. J Antibiot 73, 845–851 (2020). https://doi.org/10.1038/s41429-020-0345-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41429-020-0345-y