P117

1:Veteran’s Health Research Institute, Syracuse, NY; 2:MicuRx Pharmaceuticals, Inc., Foster City, CA

Infections caused by nontuberculous mycobacteria (NTM) have risen world-wide. Increased numbers of immunocompromised individuals, longer life expectancies for cystic fibrosis patients, better diagnostics and changes in climate are thought to be contributing factors.  Mycobacterium abscessus (MABS) is the second most frequently diagnosed NTM infection. MABS infection is extremely difficult to treat due to its intrinsic drug resistance that generally leads to complicated and largely unsuccessful long-term treatment. Treatment is often guided by susceptibility testing due to the lack of a standardized regimen. Multidrug regimens commonly include a macrolide and amikacin, but inducible and mutational resistance are problematic.

MRX-5, a prodrug, releases MRX-6038 in vivo to exert anti-MABS activity. MRX-6038, the active drug, is a novel boron-containing inhibitor of bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis. We evaluated the in vitro activity of MRX-6038 against a panel of 36 MABS clinical isolates. Clarithromycin (CLR), amikacin (AMK), clofazimine (CFZ), omadacycline (OMD), and cefoxitin (CFX) were also evaluated. MICs were determined in a broth dilution assay using CLSI methodology.

MRX-6038 demonstrated potent activity against MABS, with MIC90 and MIC50 0.25µg/ml and 0.125µg/ml, respectively. The MIC90 and MIC50 for all other compounds (µg/ml) were CLR (4, 0.5), AMK (16, 8), CFZ (4, 2), OMD (1, 0.5), and CFX (32, 8). Previously MRX-5 efficacy was demonstrated in a mouse model of pulmonary MABS infection, suggesting its potential for further development. Inherent drug resistance, lack of effective treatment, and growing numbers of infections highlight the need for new therapies to treat MABS infection.