Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating Mycobacterium tuberculosis.
Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating Mycobacterium tuberculosis.
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DOI：
10.3389/fphar.2020.616294
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发表时间：
2020
影响因子：
5.6
通讯作者：
Gumbo T
中科院分区：
文献类型：
--
作者：
Srivastava S;Cirrincione KN;Deshpande D;Gumbo T
背景资料：结核分枝杆菌（Mycobacterium tuberculosis，Mtb）在肺部病变中可存在于不同的代谢群中，而与潜伏性结核（latent tuberculosis，TB）相关的非复制型持留菌（non-replicating persisters，NRP）是最难杀灭的。 目的：在中空纤维模型[HFS-TB]中使用Mtb SS 18 b测试替地唑胺、阿托沙星和法罗培南的组合对NRP的活性。 研究方法：首先，对替地唑胺和氟诺沙星进行了测试，作为两种药物组合对对数期生长[LPG]的影响，其次，在酸性条件下缓慢复制杆菌[SRB]，并与法罗培南一起建立三种药物组合方案。最后，标准方案[异烟肼-利福平-吡嗪酰胺]在HFS-TB实验中用作NRP Mtb的对照。对HFS-TB单位进行采样，用于药物浓度测量以及使用固体琼脂和分枝杆菌生长指示管[MGIT]方法估计细菌负荷。使用线性回归计算各给药方案的杀灭斜率，并使用方差分析（ANOVA）比较各给药方案。 结果如下：在HFS-TB的杀菌和消毒活性实验中，标准剂量的泰地唑胺与高剂量的氟沙星组合分别杀死3.05 log 10 CFU/ml LPG Mtb和7.37 log 10 CFU/ml SRB。在21天内，替地唑胺-阿氟沙星-法罗培南组合与标准方案之间没有统计学差异，因为两者都杀死了7.35 log 10 CFU/ml NRP Mtb。在三个HFS-TB实验中，没有出现对任何药物的耐药性。 结论：替地唑胺、阿托沙星和法罗培南的实验方案可以有效地杀死Mtb的NRP群体，并且考虑到对Mtb的不同代谢群体的功效，可以作为泛TB方案。临床研究是必要的，以验证在体外的结果。
Background: Mycobacterium tuberculosis [Mtb] could be present in different metabolic population in the lung lesions, and nonreplicating persisters [NRP], associated with latent tuberculosis [TB], are the most difficult to kill. Objective: Test the combination of tedizolid, moxifloxacin, and faropenem for activity against NRP using Mtb SS18b in the hollow fiber model [HFS-TB]. Methods: Tedizolid and moxifloxacin were tested as, first, two-drug combination against log-phase growth [LPG] and, second, slowly replicating bacilli [SRB] under acidic condition and with faropenem to create a three-drug combination regimen. Finally, standard regimen [isoniazid-rifampin-pyrazinamide] was used as comparator in the HFS-TB experiment with NRP Mtb. HFS-TB units were sampled for drug-concentration measurement as well as for estimation of bacterial burden using solid agar and mycobacterial growth indicator tube [MGIT] method. Linear regression was used to calculate the kill slopes with each treatment regimen and analysis of variance (ANOVA) to compare the regimen. Results: Tedizolid at standard dose in combination with high-dose moxifloxacin killed 3.05 log10 CFU/ml LPG Mtb and 7.37 log10 CFU/ml SRB in the bactericidal and sterilizing activity HFS-TB experiments, respectively. There was no statistical difference between tedizolid-moxifloxacin-faropenem combination and the standard regimen as both killed 7.35 log10 CFU/ml NRP Mtb in 21 days. There was no emergence of resistance to any of the drugs studied in the three HFS-TB experiments. Conclusion: The experimental regimen of tedizolid, moxifloxacin, and faropenem could effectively kill NRP population of Mtb, and given the efficacy against different metabolic population of Mtb could serve as a pan-TB regimen. Clinical studies are warranted to validate the in vitro findings.
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影响因子：
9.6
作者：
MITCHISON, DA
通讯作者：
MITCHISON, DA
DOI：
10.1093/cid/ciw474
发表时间：
2016-11-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Deshpande D;Srivastava S;Nuermberger E;Pasipanodya JG;Swaminathan S;Gumbo T
通讯作者：
Gumbo T
影响因子：
6.4
作者：
Srivastava, Shashikant;Pasipanodya, Jotam G.;Gumbo, Tawanda
通讯作者：
Gumbo, Tawanda
影响因子：
11.8
作者：
Chilukuri, Dakshina;McMaster, Owen;Toerner, Joseph G.
通讯作者：
Toerner, Joseph G.
DOI：
10.1093/cid/ciw471
发表时间：
2016-11-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Swaminathan S;Pasipanodya JG;Ramachandran G;Hemanth Kumar AK;Srivastava S;Deshpande D;Nuermberger E;Gumbo T
通讯作者：
Gumbo T