1274 - Evaluating the Activity of SPR719, a Novel Aminobenzimidazole, against Nontuberculous Mycobacteria

Background: Pulmonary infections caused by Nontuberculous Mycobacteria (NTM) are increasing in prevalence and are associated with high mortality and morbidity.  Members of the Mycobacterium avium complex (MAC; primarily M. avium and M. intracellulare) and M. abscessus are most commonly associated with NTM pulmonary disease.  Treatment options are limited and new agents with potent activity are needed.  In this study, the activity of SPR719, a novel aminobenzimidazole, against NTM is reported.MIC range and MIC50/90 summary table


Methods: The susceptibility of 58 non-consecutive, non-duplicate clinical NTM isolates was determined in accordance with the Clinical and Laboratory Standards Institute (CLSI) standard M24.  Isolates included 20 rapidly-growing mycobacteria (10 M. abscessus/chelonae Group, 6 M. fortuitum Group, and 4 M. mucogenicum Group) and 38 slow-growing mycobacteria (28 MAC and 10 M. kansasii).  SPR719 and comparators clarithromycin (CLA), amikacin (AMK), moxifloxacin (MXF), rifabutin (RFB), minocycline (MIN), and imipenem (IPM) were evaluated.  Minimum bactericidal concentrations (MBC) for SPR719, CLA, and AMK were determined in accordance with CLSI M26.

Results: The activity of SPR719 and comparators by MIC range and MIC_50/90 (µg/mL) is summarized in the accompanying table.  SPR719 activity was not affected by resistance to CLA, AMK, or MXF.  MBC:MIC ratios for SPR719 and CLA were typically >8 which indicates a bacteriostatic mode of action; AMK MBC:MIC ratios were typically ≤ 4 indicative of bactericidal activity.

Conclusion: SPR719 had potent activity by both MIC_50/90 and MIC range across the evaluated NTM species.  The SPR719 activity against clinically relevant MAC and M. abcessus/chelonae Group isolates was comparable or superior to the evaluated comparators, and SPR719 was active against isolates resistant to currently utilized agents.  These results highlight the potential of SPR719 in the treatment of NTM pulmonary disease.