In vitro Antimicrobial Activity Comparison of Linezolid, Tedizolid, Sutezolid and Delpazolid Against Slowly Growing Mycobacteria Isolated in Beijing, China

Xia Yu,* Fengmin Huo,* Fen Wang,* Shu’an Wen, Guanglu Jiang, Yi Xue, Lingling Dong, Liping Zhao, Rui Zhu, Hairong Huang National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hairong HuangBeijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beiguan St, No. 9, Tongzhou Qu, Beijing, 101149, People’s Republic of ChinaEmail huanghairong@tb123.orgBackground: The antimicrobial activities of some new oxazolidinones against slowly growing mycobacteria (SGM) have never been well evaluated.Methods: We evaluate the in vitro susceptibility of 20 reference strains and 157 clinical isolates, pertaining different SGM species, against four oxazolidinones, ie, delpazolid, sutezolid, tedizolid and linezolid. In addition, the association of linezolid resistance and mutations in 23srRNA, rplC, rplD were also tested.Results: Sutezolid presented the strongest antimicrobial activity against the clinical isolates of M. intracellulare than the other oxazolidinones, with MIC50 at 2 μg/mL and MIC90 at 4 μg/mL. MICs of sutezolid were usually 4- to 8-fold lower than these of linezolid against M. intracellulare and M. avium. The tested isolates of M. kansasii were susceptible to all of the four oxazolidinones. According to the multiple sequence alignment, novel 23srRNA mutations (A2267C and A2266G) in M. intracellulare and rplD mutations (Thr147Ala) in M. avium were identified in this study which have plausible involvement in rendering resistance against linezolid.Conclusion: This study showed that sutezolid harbors the strongest inhibitory activity against M. intracellulare, M. avium and M. kansasii in vitro, which provided important insights on the potential clinical application of oxazolidinones for treating SGM infections.Keywords: slowly growing mycobacteria, delpazolid, sutezolid, tedizolid, linezolid, antimicrobial activity