【作者】 韩喜琴； 黄海荣； 李艳静； 于霞； 高静韬； 毕志强； 初乃惠； 李亮； 马玙；

【Author】 HAN Xi-qin~*,HUANG Hai-rong,LI Yan-jing,YU Xia,GAO,Jing-tao,BI Zhi-qiang,CHU Nai-hui,LI Liang,MA Yu * Department of Tuberculosis,Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China.

【机构】 北京市结核病胸部肿瘤研究所；

【摘要】 目的比较利福平(RFP)和利福布汀(RBT)的体外抗结核分枝杆菌活性,分析两药交叉耐药性,同时评价RFP和RBT耐药性与rpoB突变的关系。方法采用微量平板alamar blue检测法(MABA)检测RFP和RBT对168株结核分枝杆菌临床分离株的体外抗菌活性;并对该168株结核分枝杆菌的rpoB基因81个碱基对核心区的rpoB基因片段进行DNA序列测定。结果 66株RFP敏感株均对RBT敏感(MIC≤0.125ug/ml),未检测到rpoB基因耐药决定区存在突变;102株RFP耐药株中有76株同时对RBT耐药(MIC>0.5ug/ml),两药的交叉耐药率为74.5%(76/102);26株MIC≤4ug/ml的结核分枝杆菌RFP耐药株,仍对RBT敏感(MIC≤0.5ug/ml);516、526、531位氨基酸改变与RFP和RBT耐约均有关,而511、533位氨基酸改变可能仅与RFP耐药有关,RBT耐药组rpoB基因突变率显著高于敏感组(P<0.05)。结论 RFP低度耐药(MIC≤4ug/ml)的结核分枝杆菌,仍对RBT敏感。检测结核分枝杆菌rpoB基因突变可用于RFP的耐药性检测,对于RBT耐药性检测亦有参考意义。更多还原

【Abstract】 Objective:To compare the antimycobacteria activities of rifampicin(RFP) and rifabutin(RBT),We also evaluated the correlation between the level of resistance to RFP and RBT and genetic alterations in the rpoB gene.Method:The Alarmar Blue(MABA) method was performed to detect the antimycobacteria activities of RFP and RBT in 168 M.tuberculosis.Meanwhile,we also analyzed the 81bp core region of rpoB gene by DNA sequencing.Result:RBT was susceptible to all of the strains in 66 RFP-susceptible strains with no mutations in 81bp core region of rpoB gene.76 strains were also resistant to RBT in 102 RFP-resistant strains.Cross resistance between RFP and RBT was 74.5%(76/102);Alterations at codons 516,526,531 in the rpoB gene correlated with resistance to both RFP and RBT.While point mutation at codons 511 and 533 possibly influenced the susceptibility to RFP but not to RBT.The mutation rate of rpoB gene of RBT-resistant strains was significantly higher than that of RBT-susceptible strains.Conclusion: RBT was more active than RFP against M.tuberculosis.The RFP-resistant strains with MIC<4ug/ml were still susceptible to RBT.Our results suggest that analysis of genetic alterations in the rpoB gene might be useful for predicting RFP-resistance,For reference only for predicting RBT-resistance.更多还原