Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis
Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis
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DOI：
10.1128/aac.47.2.653-657.2003
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发表时间：
2003-02-01
影响因子：
4.9
通讯作者：
Mitchison, DA
中科院分区：
文献类型：
--
作者：
Hu, YM;Coates, ARM;Mitchison, DA
在三种耐利福平结核分枝杆菌持续模型中测试了环丙沙星、氧氟沙星、左氧氟沙星、莫西沙星和加替沙星的杀菌活性。模型1是100天龄、未摇动、厌氧适应的培养物，其中连续稀释的喹诺酮类药物孵育5天，然后进行CFU计数。在模型2和3中，将100毫克利福平/升添加到100天培养物中5或7天，以产生不在平板上生长的耐受生物体；然后洗掉利福平，添加新鲜培养基以恢复平板上的生长，并将培养物孵育7天，然后进行CFU计数。在模型2中，在洗掉利福平后添加喹诺酮类药物，而在模型3中，将喹诺酮类药物添加到含有利福平的培养物中。在模型I和模型2中，环丙沙星的杀菌活性最小，氧氟沙星和左氧氟沙星的活性较大，莫西沙星和加替沙星的活性最大。在模型3中，氧氟沙星没有可检测到的活性，而莫西沙星在病灶中可达到的浓度下杀死了每毫升约log(10) 0.279 CFU的持续细胞；异烟肼几乎没有活性。这些发现预测，在目前计划的临床研究中，氧氟沙星不会被发现具有有效的消毒活性，而莫西沙星将能够缩短治疗时间。
The bactericidal activities of ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin were tested in three models of rifampin-tolerant Mycobacterium tuberculosis persisters. Model 1 was a 100-day-old, unshaken, anaerobically adapted culture in which serial dilutions of the quinolones were incubated for 5 days and CFU counts were then done In models 2 and 3, 100 mg of rifampin/liter was added to the 100-day culture for 5 or 7 days to produce tolerant organisms that did not grow on plates; the rifampin was then washed off, fresh medium was added to allow recovery of growth on plates, and the culture was incubated for 7 days before CFU counts. In model 2, the quinolones were added after rifampin had been washed off, whereas in model 3 the quinolones were added to the cultures containing rifampin. In models I and 2, ciprofloxacin had the least bactericidal activity, ofloxacin and levotfloxacin had greater activities, and moxifloxacin and gatifloxacin had the greatest activities. In model 3, ofloxacin had no detectable activity whereas moxifloxacin killed about log(10) 0.279 CFU of the persisters per ml at concentrations attainable in lesions; isoniazid had virtually no activity. These findings predict that ofloxacin will not be found to have effective sterilizing activity in clinical studies now planned whereas moxifloxacin will be able to shorten treatment.