Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 61, Issue 9, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02752-16
Keywords
drug resistance; LCB01-0371; Mycobacterium abscessus; oxazolidinone
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Funding
- Korea Health Technology R&D Project through Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI15C0395]
- National Research Foundation of Korea from research funds of Chungnam National University [2016R1D1A1A02937214]
- BK21plus program through National Research Foundation (NRF) - Ministry of Education of Korea
- Gyeongsang National University
- National Research Foundation of Korea [2016R1D1A1A02937214] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Mycobacterium abscessus is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the in vitro, intracellular, and in vivo activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of M. abscessus infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several M. abscessus strains in vitro and in a macrophage model of infection. In the murine model, a similar efficacy to linezolid was achieved, especially in the lungs. We induced laboratory-generated resistance to LCB01-0371; sequencing analysis revealed mutations in rplC of T424C and G419A and a nucleotide insertion at the 503 position. Furthermore, LCB01-0371 inhibited the growth of amikacin-, cefoxitin-, and clarithromycin-resistant strains. Collectively, our data indicate that LCB01-0371 might represent a promising new class of oxazolidinones with improved safety, which may replace linezolid for the treatment of M. abscessus.
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