棋盘法检测复治新方案核心药物对耐多药和广泛耐药结核分枝杆菌体外的联合作用  

Determination of in vitro synergy by a checkerboard method when 3 core antimicrobial agents of the retreatment new scheme combined against MDR-MTB and XDR-MTB

作　　者：张琳琳[1] 杨华[1] 肖和平[1] 陆俊梅[1] 沙巍[1] 张青[1] 

机构地区：[1]上海市结核病(肺)重点实验室同济大学附属上海市肺科医院结核病临床研究中心,200433

出　　处：《中华结核和呼吸杂志》2016年第6期464-468,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的 检测“复治肺结核化学治疗新方案研究”中4种核心药物对氨基水杨酸异烟肼（PA）、莫西沙星、利福布汀及利福喷丁对耐多药MTB（MDR-MTB）和广泛耐药MTB（XDR-MTB）的体外联合作用.方法 使用棋盘法分别检测莫西沙星-PA、莫西沙星-PA-利福布汀、莫西沙星-PA-利福喷丁3种联合方案对40株临床分离耐药MTB（其中MDR-MTB和XDR-MTB各20株）和标准株H37Rv在体外联合作用时的MIC,通过计算部分抑菌浓度指数（fractional inhibitory concentration index,FICI）判断药物联合的疗效,以FICI≤0.5和FICI≤0.75作为判断2种药物和3种药物具有协同作用的依据.结果 莫西沙星-PA方案对40株耐药MTB的FICI为0.125 ～1.000,其中5株FICI≤0.5,表现为协同作用;莫西沙星-PA-利福布汀方案对20株MDR-MTB的FICI为0.310～1.260,其中10株FICI≤0.75,具有协同作用;对20株XDR-MTB的FICI为0.215 ～1.250,11株FICI≤0.75.莫西沙星-PA-利福喷丁方案对20株MDR-MTB的FICI为0.150 ～0.780,其中19株FICI≤0.75,表现为协同作用;20株XDR-MTB的FICI为0.160 ～1.280,其中16株具有协同作用.结论 莫西沙星-PA两药联合的协同作用效果较差,进一步联合利福布汀或利福喷丁则表现出一定的协同作用;利福布汀单药的抑菌效果强于利福喷丁,但莫西沙星-PA-利福布汀组合方案的协同作用效果反而较莫西沙星-PA-利福喷丁差.Objective In order to detect the in vitro synergistic effect of 4 drugs-pasiniazid （PA）,moxifloxacin,rifabutin and rifapentini on multidrug-resistant mycobacterium tuberculosis （MDR-MTB） and extensively drug-resistant mycobacterium tuberculosis（XDR-MTB）,which were core drugs of ＆quot;The program of retreatment research of tuberculosis＆quot;.Method The checkerboard method was used to detect the minimum inhibitory concentration （MIC） of antituberculosis drug combination schemes （moxifloxacin-PA,moxifloxacin-PA-rifabutin and moxifloxacin-PA-rifapentini） to 40 strains of clinical drug resistant MTB （20 strains of MDR-MTB and 20 XDR-MTB） and the standard strain H37Rv,by calculating the fractional inhibitory concentration index of joint action in vitro to judge the combined effect,with fractional inhibitory concentration index（FICI） ≤0.5 and FICI ≤ 0.75 as the basis of 2 drugs and 3 drugs showing synergy.Results The FICI of moxifloxacin-PA scheme for DR-MTB was 0.125 to 1.000,only 5 strains with a FICI ≤0.5,showing synergistic effect.The FICI of moxifloxacin-Pa-rifabutin scheme with 20 strains of MDR-MTB ranged from 0.310 to 1.260,10 strains with a FICI ≤ 0.75,showing synergistic effect.The FICI of moxifloxacin-PA-rifabutin scheme with 20 strains of XDR-MTB ranged from 0.215 to 1.250,11 strains with a FICI ≤0.75,showing synergistic effect.The FICI of moxifloxacin-PA-rifapentini scheme with 20 strains of MDR-MTB ranged from 0.150 to 0.780,19 strains with a FICI≤0.75,showing synergistic effect.The FICI of moxifloxacin-PA-rifapentini schemc with 20 strains of XDR-MTB ranged from O.200 to 1.280,16 strains with a FICI ≤ 0.75,showing synergistic effect.Conclusions The synergistic effect of moxifloxacin-PA scheme was poor,but showing better synergy when further combined with rifabutin or rifapentini.Rifabutin showed better effect than rifapentini,but the synergistic effect of moxifloxacin-PA-rifabutin combination scheme was poor than that of moxifloxacin-PA-rifapentini combination

关 键 词：分枝杆菌 结核 药物疗法 棋盘法 

分 类 号：R521[医药卫生—内科学]