Bactericidal and Sterilizing Activity of a Novel Regimen with Bedaquiline, Pretomanid, Moxifloxacin, and Pyrazinamide in a Murine Model of Tuberculosis.
Bactericidal and Sterilizing Activity of a Novel Regimen with Bedaquiline, Pretomanid, Moxifloxacin, and Pyrazinamide in a Murine Model of Tuberculosis.
复制标题
在鼠结核的鼠模型中，新型疗法，bedaquiline，pipomanid，moxifloxacin和吡嗪酰胺的杀菌性和灭菌活性。
DOI：
10.1128/aac.00913-17
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发表时间：
2017-09
影响因子：
4.9
通讯作者：
Nuermberger EL
中科院分区：
文献类型：
--
作者：
Li SY;Tasneen R;Tyagi S;Soni H;Converse PJ;Mdluli K;Nuermberger EL
寻求基于2种或更多种新型药剂的新方案以缩短或简化结核病（TB）（包括耐药形式）的治疗。先前的研究表明，在鼠TB模型中，与当前的一线方案相比，贝达喹啉（BDQ）+pretomanid（PMD）+吡嗪酰胺（PZA）和PMD+阿氟沙星（MXF）+PZA的新型组合分别缩短了预防复发所需的治疗持续时间2至3个月和1至2个月。这三种药物的组合目前正在临床试验中进行研究。在此，将BDQ + PMD + MXF + PZA的4种药物组合与其3种药物组分方案进行比较，并探索PZA和MXF的不同治疗持续时间，以确定最佳方案和治疗时间，并估计成功对抗耐药菌株的可能性。BDQ + PMD + MXF + PZA使所有小鼠在治疗2个月后无复发。PZA给药可以在治疗第一个月后停止，而不会导致结局恶化，而从一开始就没有MXF、PZA或BDQ给药则分别需要大约0.5、1或2个月的额外治疗才能达到相同的结局。
New regimens based on 2 or more novel agents are sought to shorten or to simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) plus pretomanid (PMD) plus pyrazinamide (PZA) and PMD plus moxifloxacin (MXF) plus PZA shortened the treatment duration necessary to prevent relapse by 2 to 3 months and 1 to 2 months, respectively, compared with the current first-line regimen, in a murine TB model. These 3-drug combinations are now being studied in clinical trials. Here, the 4-drug combination of BDQ+PMD+MXF+PZA was compared to its 3-drug component regimens and different treatment durations of PZA and MXF were explored, to identify the optimal regimens and treatment times and to estimate the likelihood of success against drug-resistant strains. BDQ+PMD+MXF+PZA rendered all mice relapse-free after 2 months of treatment. PZA administration could be discontinued after the first month of treatment without worsening outcomes, whereas the absence of MXF, PZA, or BDQ administration from the beginning necessitated approximately 0.5, 1, or 2 months, respectively, of additional treatment to attain the same outcome.