Multicentre evaluation of in vitro activity of contezolid against drug-resistant Staphylococcus and Enterococcus

• Published in: Journal of antimicrobial chemotherapy 2024-12, Vol.79 (12), p.3132-3141
• Main Authors: Yang, Wenhang, Li, Xue, Chen, Jiawei, Zhang, Ge, Li, Jin, Zhang, Jingjia, Wang, Tong, Kang, Wei, Gao, Haotian, Zhang, Zhijie, Liu, Yong, Xiao, Yuling, Xie, Yi, Zhao, Jianhong, Mao, Liyan, Sun, Ziyong, Li, Gang, Jia, Wei, Song, Guibo, Shan, Bin, Yu, Yanhua, Sun, Guizhen, Xu, Yingchun, Liu, Yali
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; China; Drug Resistance, Bacterial; Enterococcus - drug effects; Enterococcus - genetics; Enterococcus faecalis - drug effects; Enterococcus faecalis - genetics; Gram-Positive Bacterial Infections - microbiology; Humans; Linezolid - pharmacology; Microbial Sensitivity Tests; Mutation; Oxazolidinones - pharmacology; Pyridones; RNA, Ribosomal, 23S - genetics; Staphylococcal Infections - microbiology; Staphylococcus - drug effects; Staphylococcus - genetics; Whole Genome Sequencing
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkae331

To investigate susceptibility to contezolid, a novel oxazolidinone, multicentre surveillance was conducted involving 2449 strains of Staphylococcus and Enterococcus collected from 65 hospitals across China. The MICs of contezolid, linezolid and other clinically significant antibiotics were determined by the broth microdilution method. Consistency with the broth microdilution method for contezolid was assessed using agar dilution method, as well as disc diffusion and ETEST for linezolid, respectively. WGS was conducted on all 20 linezolid-resistant and 30 randomly non-resistant strains to analyse linezolid resistance genes (optrA, poxtA, cfr) and 23S rRNA mutation sites. All strains exhibited WT susceptibility to contezolid, while resistance proportions to daptomycin, vancomycin, teicoplanin, tigecycline and eravacycline ranged from 0% to 5.2% in Staphylococcus, and from 0% to 7.8% in Enterococcus. Linezolid resistance was higher in Enterococcus faecalis (4.4%) compared with Enterococcus faecium (0.2%). Contezolid showed a lower MIC50 (0.5 mg/L) than linezolid (2 mg/L) for methicillin-resistant Staphylococcus. Against Enterococcus, contezolid demonstrated a cumulative MIC percentage of 70% for VRE and 39.1% for E. faecalis (at MIC = 1 mg/L), whereas linezolid showed 0% and 1.1%, respectively. Among the 20 linezolid-resistant Enterococcus strains, all carried the optrA gene without 23S rRNA mutations. For contezolid, MICs were 4 mg/L for 19 strains and 2 mg/L for 1 strain. The ETEST, agar dilution and disc diffusion methods showed essential and categorical agreements of >90% for linezolid, with no major errors or very major errors. Contezolid demonstrated significant in vitro antibacterial activity against methicillin-resistant Staphylococcus, VRE and linezolid-resistant E. faecalis.