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

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.

Mycobacterium ulceranschallenge strain selection for a Buruli ulcer controlled human infection model

“…Indeed, using an arbitrary timepoint of 21 days [6] or 28 days [36] of incubation, rather than defining the MIC by comparison to an antibiotic-free growth control, may explain previous discrepancies. Nevertheless, the rifampicin MIC for JKD8049 reported here is categorised as 'susceptible' according to CLSI breakpoints [33], is similar to that reported using the agar dilution method [37], and is lower than other Victorian historical reference strains [38].…”

“…When comparing MIC values to those previously reported in the literature, the methodology presented here demonstrates the utility in diluting the growth control tube by 1:100 for M. ulcerans isolates, enabling improved resolution of MIC values. Using this methodology, JKD8049 has rifampicin and clarithromycin MICs which are similar to those determined with an agar proportion methodology [37]. The proportion method identifies a more conservative (i.e., higher) estimate for the MIC.…”

Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model

“…ulcerans isolates, enabling improved resolution of MIC values. Using this methodology, JKD8049 has rifampicin and clarithromycin MICs which are similar to those determined with an agar proportion methodology [ 36 ]. The proportion method identifies a more conservative (i.e., higher) estimate for the MIC.…”

An anti-mycobacterial conjugated oligoelectrolyte effective against Mycobacterium abscessus

“…Multiple attempts to select spontaneous mutants resistant to COE-PNH 2 were unsuccessful, indicating a frequency of resistance (FoR) below 1.25 × 10 −9 . Compared with antibiotics and drug candidates in the pipeline with an FoR between 10 −5 and 10 −8 , COE-PNH 2 is less prone to resistance development (49)(50)(51)(52)(53)(54)(55). To ensure that the FoR was not affected by changing from agar to agarose, we further conducted the test for comparator antibiotic imipenem (IPM) at 4× MIC on solid media (table S5).…”