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Abstract：
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.
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.
摘要：
我们旨在评估PBTZ169和pretomanid在体外和体内对非结核性分枝杆菌病（NTM）的活性。
11种抗生素的最低抑制浓度(MIC)，使用微孔板alamarBlue测定法对缓慢生长的分枝杆菌（SGM）和快速生长的分枝杆菌（RGM）进行了测试。bedaquiline的体内活性，氯法齐明,莫西沙星,rifabutin,在小鼠模型中评估了PBTZ169和Pretomanid对四种常见NTM的影响。
PBTZ169和pretomanid对大多数NTM参考和临床菌株的MIC>32μg/mL。然而,PBTZ169对脓肿分枝杆菌具有杀菌作用（肺和脾减少3.33和1.49log10CFU，分别）和龟分枝杆菌（肺和脾的CFU减少2.29和2.24，分别)在小鼠中，以及对鸟分枝杆菌和偶然分枝杆菌的抑菌作用。Pretomanid显着降低了脓肿分枝杆菌的CFU计数（肺和脾的CFU减少3.12和2.30log10，分别)，而它显示出适度的抑制。Bedaquiline,氯法齐明,莫西沙星在体外和体内对四种NTM均表现出良好的活性。利福布汀不抑制小鼠的鸟分枝杆菌和脓肿分枝杆菌。
PBTZ169似乎是治疗四种常见NTM感染的候选药物。Pretomanid对脓肿分枝杆菌更活跃，龟M.和M.fortuitum比对M.avium。
11种抗生素的最低抑制浓度(MIC)，使用微孔板alamarBlue测定法对缓慢生长的分枝杆菌（SGM）和快速生长的分枝杆菌（RGM）进行了测试。bedaquiline的体内活性，氯法齐明,莫西沙星,rifabutin,在小鼠模型中评估了PBTZ169和Pretomanid对四种常见NTM的影响。
PBTZ169和pretomanid对大多数NTM参考和临床菌株的MIC>32μg/mL。然而,PBTZ169对脓肿分枝杆菌具有杀菌作用（肺和脾减少3.33和1.49log10CFU，分别）和龟分枝杆菌（肺和脾的CFU减少2.29和2.24，分别)在小鼠中，以及对鸟分枝杆菌和偶然分枝杆菌的抑菌作用。Pretomanid显着降低了脓肿分枝杆菌的CFU计数（肺和脾的CFU减少3.12和2.30log10，分别)，而它显示出适度的抑制。Bedaquiline,氯法齐明,莫西沙星在体外和体内对四种NTM均表现出良好的活性。利福布汀不抑制小鼠的鸟分枝杆菌和脓肿分枝杆菌。
PBTZ169似乎是治疗四种常见NTM感染的候选药物。Pretomanid对脓肿分枝杆菌更活跃，龟M.和M.fortuitum比对M.avium。
