吡嗪酰胺
基岩
左氧氟沙星
氯法齐明
利奈唑啉
养生
药理学
利福平
肺结核
医学
化学
结核分枝杆菌
抗生素
利福喷丁
异烟肼
莫西沙星
内科学
微生物学
免疫学
生物
麻风病
病理
万古霉素
金黄色葡萄球菌
细菌
遗传学
作者
Wei Yu,Yusuf Buhari,Shuai Wang,Xirong Tian,H.M. Adnan Hameed,Zhili Lu,Gift Chiwala,Shah Jamal Alam,Gregory M. Cook,Dmitry L. Maslov,Nanshan Zhong,Tianyu Zhang
标识
DOI:10.1101/2021.04.04.438375
摘要
ABSTRACT Toxicity and inconvenience associated with the use of injectable drug-containing regimens for tuberculosis (TB) have made all-oral regimens a preferred alternative. Widespread resistance to fluoroquinolones and pyrazinamide makes it essential to identify new drug candidates and study their effects on current regimens for TB. TB47 is a pyrazolo[1,5-a]pyridine-3-carboxamide with powerful synergistic in vitro and in vivo activities against mycobacteria, especially with clofazimine. Here, we investigated the bactericidal and sterilizing activities of novel oral regimens containing TB47 + clofazimine + linezolid, and the potential roles of levofloxacin and/or pyrazinamide in such drug combinations. Using a well-established mouse model, we assessed the effect of these regimens on bacterial burden in the lung during treatment and relapse (4 months after stopping treatment + immunosuppression). Our findings indicate that the TB47 + clofazimine + linezolid + pyrazinamide, with/without levofloxacin, regimens had fast-acting (4 months) sterilizing activity and no relapse was observed. When pyrazinamide was excluded from the regimen, treatment times were longer (5-6 months) to achieve sterilizing conditions. We propose that TB47 + clofazimine + linezolid can form a highly sterilizing block for use as an alternative pan-TB regimen.
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