Nat Commun:美学者揭示优化抗生素组合可改善肺结核疗法

2017年1月24日,国际学术权威刊物自然出版集团旗下子刊《Nature Communications》杂志在线发表了美国加州大学Marcus A. Horwitz研究员的一篇研究论文,研究显示优化抗生素组合及其剂量可以大幅缩短肺结核小鼠模型的治疗时间。

目前针对肺结核的抗生素疗法一般需要综合使用4种抗生素治疗6-8个月,但是这种疗法通常会引起不良反应,许多病人都无法完成治疗。Marcus Horwitz及同事在被感染的小鼠身上,测试了大量可能的抗生素组合和剂量类型,然后使用数学模型分析所得信息以预测最有效的药物-剂量组合。他们表明,与标准疗法相比,两种富有潜力的新疗法可以更快速地杀死小鼠肺结核细菌,并将无复发治愈所需的治疗时间最多缩短75%。

作者此前在体外感染模型上使用了类似的方法,当时采用的是培养的巨噬细胞而非小鼠。但是,目前的研究在活体动物身上验证了药物-剂量组合的安全性和有效性,这具有重要意义,不过还需要做进一步的研究以检验以上发现是否可以转化至人类身上。

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原文摘要:

The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model ofMycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis.