In Vitro Antimicrobial Activity of Contezolid Againstand Absence of Cross-Resistance with Linezolid.

Tuberculosis (TB) persists as a formidable global health threat, especially with the rising incidence of multidrug-resistant strains. This study aimed to evaluate the in vitro activity of contezolid, a novel oxazolidinone antibiotic, against() and assess potential cross-resistance with linezolid. Thirty-oneclinical isolates (5 susceptible, 8 multidrug-resistant [MDR], 18 pre-extensively drug-resistant [pre-XDR]) were tested. Minimum inhibitory concentrations (MICs) of contezolid and linezolid were determined, along with mutation resistance frequencies. Intracellular replication inhibition in macrophages and whole-genome sequencing of resistant colonies were assessed. Cytotoxicity was evaluated via luciferase-coupled ATP assay. The MIC50 and MIC90 values of contezolid were comparable to those of linezolid. Contezolid induced higher mutation frequencies in 7 isolates. At 12 mg/L, both drugs similarly inhibited intracellularreplication. Whole-genome sequencing revealed that thegene was linked to contezolid resistance, with no cross-resistance observed between two drugs. No significant cytotoxicity was observed in contezolid-treated mouse peritoneal macrophages (> 0.05). Contezolid exhibits anti-activity, withpotentially associated with resistance. No cross-resistance with linezolid was found.