In vitro evaluation of the antibacterial activities of radezolid and linezolid for Streptococcus agalactiae

Purpose: This study aims to evaluate the antimicrobial activities of linezolid and radezolid against Streptococcus agalactiae in vitro and compared for genetic resistance factors. Method Nonduplicate S. agalactiae clinical isolates (n = 136) were collected and the minimal inhibitory concentrations of antimicrobials were determined by agar dilution methodology. The linezolid-resistant mechanism in the clinical linezolid-non-susceptible S. agalactiae isolates and that induced by linezolid pressure in vitro were analyzed by PCR and sequence alignment. Antimicrobial activities and resistance mechanism distinctions between linezolid and radezolid were further investigated in the clinical linezolid-non-susceptible S. agalactiae isolates and that induced by linezolid pressure in vitro. Results: Our data indicated that 17 (13%) of the 136 clinical S. agalactiae isolates were not susceptible to linezolid. For individual S. agalactiae isolates, including linezolid-nonsusceptible isolates with 23S rRNA V domain mutations, radezolid MIC90 values were generally one-half to one-quarter of the linezolid MIC90 values. Radezolid MICs remained low relative to linezolid MICs among linezolid-resistant S. agalactiae isolates, but exhibited the synchronous increases with the increasing copy numbers of 235 rRNA V domain mutations. Overall, 13 optrA-carrying clinical S. agalactiae isolates were found in this study and their MICs all remained sensitive to both linezolid and radezolid. Clinical S. agalactiae isolates with high radezolid MICs showed clonality clustering to sequence type (ST)10. Conclusion: Radezolid exhibits stronger potency against S. agalactiae than linezolid and there is a concerning presence of linezolid-nonsusceptible S. agalactiae in clinical samples.