Abstract
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.
Highlights
Non-tuberculosis mycobacteria (NTM) is a catch-all descriptor for mycobacteria other than Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively
While not all NTM are capable of causing human infections, several species including Mycobacterium abscessus, Mycobacterium avium, Mycobacterium ulcerans, Mycobacterium marinum, and Mycobacterium chimaera can cause a range of infections in different organs and at different anatomical sites, including the lungs, skin, subcutaneous tissue and cardiac associated prosthetic medical devices
To further investigate the activity of SPR719 on the tested M. ulcerans, M. marinum and M. chimaera isolates, we looked at gyrase subunit B (GyrB) residues that have previously been associated with decreased SPR719 susceptibility
Summary
Non-tuberculosis mycobacteria (NTM) is a catch-all descriptor for mycobacteria other than Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively. While not all NTM are capable of causing human infections, several species including Mycobacterium abscessus, Mycobacterium avium, Mycobacterium ulcerans, Mycobacterium marinum, and Mycobacterium chimaera can cause a range of infections in different organs and at different anatomical sites, including the lungs, skin, subcutaneous tissue and cardiac associated prosthetic medical devices. M. ulcerans causes the neglected tropical skin disease known as Buruli ulcer (BU) [2]. First presenting as a small nodule, if left untreated lesions can ulcerate and without proper diagnosis and treatment can lead to significant morbidity and long term disability [4]. The introduction of a fully oral treatment regimen by the WHO (utilizing clarithromycin and rifampicin) has revolutionized BU treatment [6]; there are still issues associated with the length of treatment (8 weeks), tolerability and access to the antibiotics, presenting opportunities to further improve this regimen
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