In vitro activity of SPR719 against Mycobacterium ulcerans, Mycobacterium marinum and Mycobacterium chimaera

Nontuberculosis mycobacterial (NTM) infections are increasing in prevalence across the world. In many cases, treatment options for these infections are limited. However, there has been progress in recent years in the development of new antimycobacterial drugs. Here, we investigate the in vitro activity of SPR719, a novel aminobenzimidazole antibiotic and the active form of the clinical-stage compound, SPR720, against several isolates of Mycobacterium ulcerans, Mycobacterium marinum and Mycobacterium chimaera. We show that SPR719 is active against these NTM species with a MIC range of 0.125–4 μg/ml and that this compares favorably with the commonly utilized antimycobacterial antibiotics, rifampicin and clarithromycin. Our findings suggest that SPR720 should be further evaluated for the treatment of NTM infections.
Author summary Nontuberculosis mycobacteria represent a large group of diverse bacteria that live across a range of environments. Human contact with the habitats in which these organisms live can result in opportunistic infections. Among the NTM, Mycobacterium ulcerans causes necrotic skin ulcers that can lead to significant long term physical impairment; Mycobacterium marinum causes granulomatous skin lesions; and Mycobacterium chimaera has been linked to contaminated heater-cooler units used during cardiac surgery, resulting in prosthetic heart valve infections that are particularly difficult to treat. We performed laboratory experiments to test the susceptibility of these NTM species (M. ulcerans, M. marinum and M. chimaera) to a recently developed antibiotic, SPR719. We found that SPR719 inhibits the growth of these mycobacteria at concentration ranges similar to or better than commonly used anti-mycobacterial antibiotics. As SPR720, the oral prodrug of SPR719, has recently completed a Phase I safety, tolerability and PK study in healthy human volunteers, the potential exists for this product to be explored for the treatment of NTM infections, where new treatment options are urgently needed.