Open AccessActivity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus
Author(s) -
Tae Sung Kim,
Jin Ho Choe,
Young Jae Kim,
Chul–Su Yang,
HyunJin Kwon,
Jinsun Jeong,
Guehye Kim,
Da Eun Park,
EunKyeong Jo,
Young Lag Cho,
Jichan Jang
Publication year - 2017
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02752-16
Subject(s) - mycobacterium abscessus , microbiology and biotechnology , clarithromycin , amikacin , linezolid , nontuberculous mycobacteria , rifamycin , cefoxitin , antibiotics , chemistry , mycobacterium , in vivo , in vitro , rifabutin , biology , bacteria , staphylococcus aureus , biochemistry , genetics , vancomycin
Mycobacterium abscessus is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated thein vitro , intracellular, andin vivo activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment ofM. abscessus infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against severalM. abscessus strainsin 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 inrplC 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 ofM. abscessus .
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