一线抗痨药物均耐药结核菌体外组合药物作用效果研究  

In vitro effects of combinatorial drugs against multidrug-resistant mycobacterium tuberculosis*

作　　者：王易伟[1] 胡频频[1] 张西雁[1] 王宇[1] 钟静[1] 包佳玲[1] 钟敏[1] 

机构地区：[1]重庆市肺科医院

出　　处：《重庆医学》2009年第14期1762-1763,1766,共3页Chongqing medicine

基　　金：重庆市医学科研基金资助项目(05-2-225)。

摘　　要：目的对临床主要一线抗痨药异烟肼(isoniazidum,H)、利福平(rifampin,R)、链霉素(streptomycin,S)和乙胺丁醇(ethambatal,E)均耐药结核菌株进行体外组合药物作用效果研究,拟探讨结核病主要一线药物均耐药再联合用药时,化疗是否有效的临床耐多药结核病治疗问题。方法采用BacT/ALERT 3D分支杆菌培养系统对10株常规L-J法药敏至少对H、R、S和E(或同时对R)依赖的结核菌株及H37Rv标准敏感菌株,以MIC和平均血药峰浓度分别进行H、R、S及E单一药物和H+E+S及H+S+E+R组合药物药敏平行实验;将3D培养42d结果为阴性的实验瓶混悬液再平行转种于L-J管继续培养,以确定药物作用的效果(观察细菌是否真正被药物杀死)。结果单一药物3D法与L-J法的药敏结果基本一致。3D法单一药物均耐药菌株组合药物MIC和平均血药峰浓度实验结果显示不同程度报告阳性时间延长趋势。3D法单一药物耐药,组合药物未报告阳性的实验瓶,转种于L-J管继续培养均报告阳性。病例追踪10株分离株均为一线正规化疗失败的复治肺结核患者。结论小样本菌株实验研究结果提示:体外3D法H、R、S及E单一药物均耐药的临床结核菌株,组合药物(MIC和平均血药峰浓度)对其细菌可有不同程度的相对抑制作用,但没有最终协同杀灭细菌,其实验结果与患者临床疗效相符合。Objective To evaluate the in vitro effects of combinatorial drugs of rifampicin,isoniazid,streptomycin and ethambu tol against multidrug-resistant Mycobacterlum tuberculosis（MDR-TB） strains,and further discuss the efficacy of chemotherapy by using combinatorial drugs to treat multidrug-resistance tuberculosis clinically. Methods Clinical isolated Mycobacterium tuberculosis（MTB） strains were cultured on Lowenstein-Jensen（L-J） medium. Then 10 MDR-TB strains were screened and cultured by MTB/BacT ALERT 3D system. The in vitro effects of combinatorial drugs or each drug respectively on MDR-TB strains or H37Rv strain were evaluated by MIC （minimum inhibitory concentration） and Cmax in blood. To further test the bacteria killing effects of these drugs,suspension of 3D negative culture was transferred to LJ medium after 42 days. Results The outcomes of single drug treatment in 3D system were consistent with the outcomes in L-J medium. Combinatorial drugs treated MDR-TB strains remained longer as MIC and Cmax negative in 3D system. However,further cultivation in L-J medium after transferring turned back to positive. Case report indicated that those 10 strains were all from re-examined patients who failed the regular chemotherapy. Conclusion This small-sample experiment indicates that combinatorial drugs are able to inhibit MDR-TB strains （MIC and Cmax）,but have no killing effects in a synergistic way. This is consistent with the clinical outcomes of TB patient treatment.

关 键 词：分支杆菌 结核 3D分支杆菌培养系统 组合药敏实验 耐多药结核病 

分 类 号：R96[医药卫生—药理学]