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Antimicrob Agents Chemother. 2017 Aug 24;61(9). pii: e02752-16. doi: 10.1128/AAC.02752-16. Print 2017 Sep.

Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus.

Author information

1
Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea.
2
Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea.
3
Department of Molecular and Life Science, Hanyang University, Ansan, South Korea.
4
LegoChem Biosciences, Inc., Daejeon, South Korea.
5
Division of Applied Life Science (BK21plus Program), Gyeongsang National University, Jinju, South Korea.
6
Division of Applied Life Science (BK21plus Program), Gyeongsang National University, Jinju, South Korea jichanjang@gnu.ac.kr.
7
Division of Life Science, Research Institute of Life Sciences, Gyeongsang National University, Jinju, South Korea.

Abstract

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.

KEYWORDS:

LCB01-0371; Mycobacterium abscessus; drug resistance; oxazolidinone

PMID:
28674049
PMCID:
PMC5571369
DOI:
10.1128/AAC.02752-16
[Indexed for MEDLINE]
Free PMC Article

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