磺胺类药物对结核分枝杆菌的体外抑菌作用及与其他抗结核药物相互作用的研究  

The anti-mycobacterial efficacy of sulfamethoxazole combined with trimethoprim and the interaction with other anti-tuberculosis drugs in vitro

作　　者：于霞[1,2] 赵立平[1,2] 姜广路[1,2] 马异峰[1,2] 黄海荣[1,2] 

机构地区：[1]北京市结核病胸部肿瘤研究所 [2]首都医科大学附属北京胸科医院国家结核病临床实验室,101149

出　　处：《中国防痨杂志》2013年第6期433-438,共6页Chinese Journal of Antituberculosis

基　　金：北京市重大科技攻关项目(D121100003012001)

摘　　要：目的评价磺胺甲噁唑(sulfamethoxazole,SMX)和甲氧苄啶(trimethoprim,TMP)对结核分枝杆菌的体外抑菌作用,并探讨SMX与其他抗结核药物的体外相互作用。方法采用微孔板Alamar blue法测定TMP联合SMX对121株结核分枝杆菌临床株的最低抑菌浓度(MIC)。同时采用分层整群抽样设计方法,抽取18株结核分枝杆菌临床分离株观察SMX在与利福平、异烟肼、链霉素、乙胺丁醇、卡那霉素、氧氟沙星、利福布丁联用时MIC值的影响,以H37Rv为对照,通过计算分级抑菌浓度指数(FICI),观察SMX与其他抗结核药物之间是否存在协同作用。采用SPSS 13.0统计软件进行统计学分析,MDR菌株、非MDR菌株、敏感菌株间MIC的比较采用非参数秩和检验,以P<0.05为差异有统计学意义。结果90.08%(109/121)的结核分枝杆菌临床分离株可以被MIC为1/19(TMP∶SMX)μg/ml的复合制剂抑制生长,5株菌株的"TMP∶SMX=1∶19"的MIC为2/38μg/ml,仅有7株"TMP∶SMX=1∶19"的MIC≥2/38μg/ml,包括敏感株5株,MDR菌株2株。"TMP∶SMX=1∶19"对敏感株、MDR菌株及非MDR菌株MIC间的差异没有统计学意义(χ2=0.111,P=0.946)。对于H37Rv,SMX与其他抗结核药联合用药后,除了利福布丁表现出协同作用(FICI为0.281)外,其余药物均表现为无关作用。对18株临床分离株,SMX与其他抗结核药联合用药后,77.78%(14/18)表现为与利福布丁协同,FICI范围为0.205～1.063。结论TMP联合SMX有较好的抗结核分枝杆菌活性,并且这种活性与细菌对其他药物是否耐药无关;SMX与其他常用抗结核药的相互作用主要表现为无关。Objective To evaluate the anti-mycobacterial efficacy of sulfamethoxazole（SMX）and trimethoprim（TMP） on Mycobacterium tuberculosis and analyze the interaction between SMX and other anti-TB drugs in vitro.Methods The minimum inhibition concentrations（MICs） of TMP/SMX in 121 Mycobacterium tuberculosis（Mtb） strains were tested by microplate alamar blue assay（MABA）.Eighteen clinical isolates were chosen by the stratified cluster sample method,and determined the interactions between SMX and rifampicin,isoniazid,streptomycin,ethambutol,kanamycin,ofloxacin,rifabutin in vitro by fractional inhibitory concentration index（FICI） method.Meanwhile,Mtb H37Rv strain was used as reference.The data were analyzed using SPSS software-version 13.0,nonparametric rank sum text was adopted for comparing the MIC of 3 groups,statistically significant difference was P0.05.Results 90.08%（109/121） isolates of Mtb could be inhibited by 1/19 μg/ml TMP/SMX.The MIC of TMP/SMX（1∶19） in 5 isolates was 2/38 μg/ml,7 strains including 5 drug-sensitive strains and 2 MDR strains with MIC≥2/38 μg/ml.The MICs of TMP/SMX（1∶19） had no statistical significance among drug-sensitive strains,MDR strains and other drug-resistant strains（χ2=0.111,P=0.946）.Drug combination testing did not display synergy between SMX and 7 other anti-TB drugs on H37Rv strain,except for with rifabutin（FICI 0.281）.Among 18 clinical isolates,14（14/18,77.78%） exhibited synergy between SMX and rifabutin,in which FICI ranged from 0.205 to 1.063.Conclusion TMP/SMX showed great anti-mycobacterical efficacy on Mtb clinical isolates in vitro,regardless of drug-resistant patterns.There were no synergy between SMX and 7 other anti-TB drugs in vitro,except for rifabutin.

关 键 词：磺胺甲噁唑 甲氧苄啶 抗结核药 微生物敏感性试验 药物相互作用 

分 类 号：R96[医药卫生—药理学]