Evaluation of the Efficacy of Novel Oxazolidinone Analogues against Nontuberculous Mycobacteria In Vitro

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  • Zhao Weiguo
    Department of Respiratory Medicine, The 309th Hospital of People's Liberation Army
  • Jiang Ying
    Department of Clinical Laboratory, The 309th Hospital of People's Liberation Army
  • Bao Pengtao
    Department of Respiratory Medicine, The 309th Hospital of People's Liberation Army
  • Li Yun
    Department of Respiratory Medicine, The 309th Hospital of People's Liberation Army
  • Tang Liping
    Department of Respiratory Medicine, The 309th Hospital of People's Liberation Army
  • Zhou Yi
    Department of Respiratory Medicine, The 309th Hospital of People's Liberation Army
  • Zhao Yanfang
    School of Pharmaceutical Engineering, Shenyang Pharmaceutical University

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Nontuberculous mycobacteria (NTM) are associated with a number of clinical diseases and only a few antitubercular agents are active against them. Oxazolidinones comprise a novel class of antimicrobials that inhibit bacterial protein synthesis at the ribosome. Linezolid, the first oxazolidinone antibacterial agent approved for clinical use, has excellent activity against some NTM but is ineffective against others. Sy142 and sy144 are novel oxazolidinones with demonstrated activties against Mycobacterium tuberculosis and Staphylococcus aureus. In this work, we compared the susceptibilities of key NTM species to linezolid, sy142, and sy144. The organisms included 21 isolates of Mycobacterium abscessus, 31 of Mycobacterium avium, 11 of Mycobacterium chelonae, 24 of Mycobacterium fortuitum, 26 of Mycobacterium kansasii, and 17 of Mycobacterium intracellulare. For M. kansasii and M. fortuitum, linezolid showed excellent antimicrobial activity, and an equal MIC range was found in sy142 and sy144. For the species that linezolid was less active against, sy142 and sy144 showed greater antimicrobial activities or exhibited equal compared to linezolid. Particularly, for M. avium and M. intracellulare, the in vitro antimicrobial activity of sy142 was 4-fold higher than that of linezolid. These results demonstrate the potential of these compounds to treat NTM infections.

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