Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Global Alliance for Tuberculosis Drug Development, New York, New York, USA.
Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.00913-17. Print 2017 Sep.
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.
新的方案基于 2 种或更多的新型药物，旨在缩短或简化结核病（TB）的治疗，包括耐药形式。先前的研究表明，贝达喹啉（BDQ）加丙硫异烟胺（PMD）加吡嗪酰胺（PZA）的新型组合以及 PMD 加莫西沙星（MXF）加 PZA 的新型组合，与目前的一线方案相比，分别缩短了 2 至 3 个月和 1 至 2 个月的治疗时间，以预防复发，在鼠类结核病模型中。这些三药组合目前正在临床试验中进行研究。在这里，BDQ+PMD+MXF+PZA 的四药组合与三药组成方案进行了比较，并探索了 PZA 和 MXF 的不同治疗时间，以确定最佳方案和治疗时间，并估计对耐药菌株成功的可能性。BDQ+PMD+MXF+PZA 在 2 个月的治疗后使所有小鼠均无复发。在第一个月的治疗后可以停止使用 PZA 而不会使结果恶化，而从一开始就没有使用 MXF、PZA 或 BDQ 治疗，则需要分别再额外治疗大约 0.5、1 或 2 个月，以达到相同的结果。
