In Vitro Susceptibility Testing of a Novel Benzimidazole, SPR719, against Nontuberculous Mycobacteria

Nontuberculous mycobacterium (NTM) infections are increasing globally. The Mycobacterium avium complex (MAC) and Mycobacterium abscessus are the most frequently encountered NTM among clinical laboratories, and treatment options are extremely limited. In this study, the in vitro potency of a novel benzimidazole, SPR719, the microbiologically active form of the orally available prodrug SPR720, was tested against several species of NTM. MICs were determined for 161 isolates of NTM of 13 taxa (seven species, three subspecies, and three groups/complexes) in cation-adjusted Mueller-Hinton Broth, as described and recommended by the Clinical and Laboratory Standards Institute (CLSI M24-A2). Comparator antimicrobials included amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin, tigecycline, and trimethoprim-sulfamethoxazole (TMP-SMX) for the rapidly growing mycobacteria (RGM), amikacin and clarithromycin for the MAC, and amikacin, ciprofloxacin, clarithromycin, doxycycline, linezolid, moxifloxacin, rifabutin, rifampin, and TMP-SMX for the other slowly growing NTM. SPR719 was found to be potent against multiple clinical strains of NTM with an MIC50 range of 0.25 to 4 mu g/ml for several species of NTM. These findings support the further advancement of SPR720 for the treatment of NTM disease.