2135. Epetraborole in vitro Activity Against Mycobacterium avium complex Recent Clinical Isolates from Japan

Abstract

Abstract Background Epetraborole (EBO) is a boron-containing, oral inhibitor of bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis. EBO demonstrates potent activity against nontuberculous mycobacteria and is currently under clinical development for treatment of treatment-refractory Mycobacterium avium complex (MAC) lung disease. The objective of this study was to evaluate the in vitro activity of EBO against recent MAC isolates from Japan. Methods Minimal inhibitory concentration (MIC) values for EBO, amikacin (AMK), clarithromycin (CLR), rifabutin (RFB), and ethambutol (EMB) were determined using broth microdilution assays according to Clinical and Laboratory Standards Institute M24-A3 guideline (2018) against 110 MAC clinical isolates collected from Japanese patients in 2020. MAC isolates were of respiratory origin and included 55 M. avium and 55 M. intracellulare isolates. Results EBO (MIC) values ranged from 0.25 - 16 µg/mL and the EBO MIC50 and MIC90 were 2 and 4 µg/mL, respectively (Table 1). The CLR MIC range was 0.125 - > 32 µg/mL and included 4 CLR-resistant isolates (MIC ≥ 32 µg/mL). CLR MIC50 and MIC90 were 1 and 4 µg/mL, respectively. All isolates were susceptible to AMK and had an MIC range of 2 - 32 µg/mL; the MIC50 and MIC90 were 8 and 16 µg/mL, respectively. The EMB MIC range was 2 - > 32 µg/mL; the MIC50 and MIC90 were 4 and 16 µg/mL, and the RFB MIC range was ≤0.03 - 2 µg/mL and MIC50 and MIC90 were 0.06 and 0.25 µg/mL. EBO maintained activity with MIC values of 0.25 - 2 µg/mL against the 4 CLR-resistant isolates. Epetraborole and comparator antimicrobial minimum inhibitory concentration values against 110 recent Mycobacterium avium complex clinical isolates from Japan MIC=minimal inhibitory concentration; MIC50=minimal inhibitory concentration for 50% of isolates tested; MIC90=minimal inhibitory concentration for 90% of isolates tested. Conclusion EBO demonstrated potent in vitro activity against 110 recent MAC isolates collected from Japanese patients. Furthermore, EBO demonstrated in vitro activity against CLR-resistant MAC isolates suggesting that CLR-resistance does not impact EBO activity. These data are similar to results obtained against U.S. isolates and support the continued clinical evaluation of the use of EBO in the treatment of MAC lung disease in Japan. Disclosures Tiffany Keepers White, PhD, AN2 Therapeutics: Employee|AN2 Therapeutics: Stocks/Bonds Satoshi Mitarai, MD, PhD, AN2 Therapeutics, Inc.: Grant/Research Support