Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis (MTB). In this study, we compared in vitro activity and minimal inhibitory concentration (MIC) distributions between delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant (MDR) and extensively drug-resistant MTB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC and rplD genes were analyzed to reveal potential mechanism(s) underlying observed oxazolidinone resistance. A total of 240 MTB isolates were enrolled in this study, including 120 MDR-TB and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for MTB isolates were 0.25 mg/L and 0.5 mg/L, respectively. Based upon visual inspection, we tentatively set epidemiological cutoff values (ECOFFs) for MIC determinations at 1.0 mg/L and 2.0 mg/L for linezolid and delpazolid, respectively. Although no significant difference in resistance rate was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly higher proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, one isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC > 16 mg/L) compared to a delpazolid MIC = 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity is comparable to that of linezolid. A novel mutation within rplD was identified that endowed MTB with linezolid, but not delpazolid, resistance.
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