We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) in vitro and in vivo.

The minimum inhibitory concentrations (MICs) of 11 antibiotics, against slow-growing mycobacteria (SGMs) and rapid-growing mycobacteria (RGMs) were tested using the microplate alamarBlue assay. The in vivo activities of bedaquiline, clofazimine, moxifloxacin, rifabutin, PBTZ169 and pretomanid against four common NTMs were assessed in murine models.

PBTZ169 and pretomanid had MICs of >32 μg/mL against most NTM reference and clinical strains. However, PBTZ169 was bactericidal against Mycobacterium abscessus (3.33 and 1.49 log10 CFU reductions in the lungs and spleen, respectively) and Mycobacterium chelonae (2.29 and 2.24 CFU reductions in the lungs and spleen, respectively) in mice, and bacteriostatic against Mycobacterium avium and Mycobacterium fortuitum. Pretomanid dramatically decreased the CFU counts of M. abscessus (3.12 and 2.30 log10 CFU reductions in the lungs and spleen, respectively), whereas it showed moderate inhibition of M. chelonae and M. fortuitum. Bedaquiline, clofazimine, and moxifloxacin showed good activities against four NTMs in vitro and in vivo. Rifabutin did not inhibit M. avium and M. abscessus in mice.

PBTZ169 appears to be a candidate for treating four common NTM infections. Pretomanid was more active against M. abscessus, M. chelonae and M. fortuitum than against M. avium.

我们旨在评估 PBTZ169 和 pretomanid 对非结核分枝杆菌病 (NTM) 的活性体外和体内.

使用微孔板 alamarBlue 测定法测试了 11 种抗生素对缓慢生长的分枝杆菌 (SGM) 和快速生长的分枝杆菌 (RGM) 的最低抑菌浓度 (MIC)。这体内在小鼠模型中评估了贝达喹啉、氯法齐明、莫西沙星、利福布汀、PBTZ169 和 pretomanid 对四种常见 NTM 的活性。

PBTZ169 和 pretomanid 对大多数 NTM 参考和临床菌株的 MIC > 32 μg/mL。然而，PBTZ169 对脓肿分枝杆菌（肺和脾分别减少 3.33 和 1.49 log10 CFU）和龟分枝杆菌（肺和脾脏分别减少 2.29 和 2.24 CFU）小鼠，以及对鸟分枝杆菌和偶发分枝杆菌. Pretomanid 显着降低了 CFU 计数脓肿分枝杆菌（肺和脾脏分别减少 3.12 和 2.30 log10 CFU），而它对龟分枝杆菌和M.偶然. 贝达喹啉、氯法齐明和莫西沙星对四种 NTM 表现出良好的活性体外和体内. 利福布丁没有抑制作用鸟分枝杆菌和脓肿分枝杆菌在小鼠中。

PBTZ169 似乎是治疗四种常见 NTM 感染的候选药物。Pretomanid 更积极地反对脓肿分枝杆菌,龟分枝杆菌和M.偶然比反对鸟分枝杆菌.