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

Abstract

<i>Mycobacterium abscessus</i> is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the <i>in vitro</i>, intracellular, and <i>in vivo</i> activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of <i>M. abscessus</i> infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several <i>M. abscessus</i> strains <i>in vitro</i> 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 <i>rplC</i> 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 <i>M. abscessus</i>.