Characterization of Mouse Models of Mycobacterium avium Complex Infection and Evaluation of Drug Combinations
Characterization of Mouse Models of Mycobacterium avium Complex Infection and Evaluation of Drug Combinations
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DOI：
10.1128/aac.04841-14
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发表时间：
2015-04-01
影响因子：
4.9
通讯作者：
Grosset, Jacques H.
中科院分区：
文献类型：
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作者：
Andrejak, Claire;Almeida, Deepak V.;Grosset, Jacques H.
鸟分枝杆菌复合体是全世界非结核分枝杆菌肺病最常见的病因，然而，对鸟分枝杆菌复合体的最佳治疗方案是：尚未确定是否存在禽流感复合体感染。克拉霉素是公认的治疗M的基础药物。然而，需要良好的模型系统，特别是动物模型来评估最有效的伴随药物。我们进行了一系列的实验，以评估和使用不同的小鼠模型（比较BALB/c，C57 BL/6，裸鼠和米色小鼠）的M。禽支原体感染，并评估抗M.体外、离体和小鼠中单一和组合药物方案的禽流感活性。克拉霉素和阿托沙星在体外对M.两药间无拮抗作用。裸鼠对M.与其他测试的小鼠品系相比，治疗的影响在M. avium感染中最为明显。禽流感病毒感染的BALB/c小鼠。在所有感染小鼠中，克拉霉素-乙胺丁醇-利福平联合用药比克拉霉素-乙胺丁醇利福平更有效;在含克拉霉素的方案中加入阿托沙星并没有增加治疗疗效。含克拉霉素的方案对M.禽流感感染;用阿托沙星替代克拉霉素对治疗效果有负面影响。
The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutolrifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin- containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy.