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

作者：Kim Tae Sung; Choe Jin Ho; Kim Young Jae; Yang Chul Su; Kwon Hyun Jin; Jeong Jinsun; Kim Guehye; Park Da Eun; Jo Eun Kyeong; Cho Young Lag; Jang Jichan^*

来源：Antimicrobial Agents and Chemotherapy, 2017, 61(9): e02752-16.

DOI：10.1128/AAC.02752-16

• drug resistance
• LCB01-0371
• Mycobacterium abscessus
• oxazolidinone

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.

• 出版日期2017-9