131株耐多药结核分枝杆菌对利福布丁与利福平交叉耐药的研究

doi:10.3969/j.issn.1000-6621.2015.04.010

摘要/Abstract

摘要： 目的观察利福布丁对MDR-TB菌株的抑菌效力及其与利福平的交叉耐药性，了解对利福布丁与利福平交叉耐药菌株rpoB基因突变特征。方法采用间隔抽样法，从2007—2008年全国结核病耐药基线调查的401株MDR-TB菌株中抽样，传代后获得131株MDR-TB菌株。用微孔板Alamar blue法测定利福平和利福布丁对MDR-TB菌株的最低抑菌浓度（MIC），采用直接测序法检测MDR-TB菌株rpoB基因突变，分析rpoB基因突变对两者交叉耐药性的影响。采用SPSS 11.0软件进行统计分析，交叉耐药率比较采用χ²检验，P<0.05为差异有统计学意义。结果在131株MDR-TB菌株中，利福平MIC中位数值为256 μg/ml，利福布丁MIC中位数值为2 μg/ml。通过测定MIC的方法，利福平与利福布丁交叉耐药率为76.47%（91/119）。在MDR-TB菌株中，发生rpoB基因突变113株（86.26%，113/131），包括531、526、516、513、511、522、533等7种单位点突变，其中以密码子531（56.50%，74/131）、526（16.03%，21/131）突变最为常见。不同rpoB基因突变的MDR-TB菌株，526、531位点突变出现利福平与利福布丁交叉耐药的比例最高，分别占90.48%（19/21）、78.38%（58/74），与无突变组（44.44%，8/18）比较，差异均有统计学意义（χ²值分别为9.641、8.223，P值均＜0.05）。结论利福布丁与利福平存在交叉耐药性，但利福布丁有更强的抑菌能力。MDR-TB菌株不同rpoB突变类型，利福平与利福布丁交叉耐药性不同。

关键词: 结核分枝杆菌, 抗药性, 多种, 细菌, 利福布丁, 利福平, 微生物敏感性试验, 细菌蛋白质类

Abstract: Objective To investigate the antibacterial effect of rifabutin and the cross-resistance between rifabutin and rifampin in multidrug-resistant Mycobacterium tuberculosis（MDR-TB）strains, to understand the mutation characteristics of rpoB gene among the strains with rifampin and rifabutin cross-resistance. Methods Using interval sampling method, 131 MDR-TB clinical strains were obtained from 401 MDR-TB isolates of National Drug Resistance Tuberculosis Baseline Survey in 2007—2008. Minimum inhibitory concentrations (MICs) of rifampin and rifabutin for these MDR-TB isolates were determined by microplate Alamar blue assay method.The mutations of rpoB gene were determined by DNA sequencing, and analyzed the effect of the rpoB gene mutations on rifabutin and rifampin cross resistance. Using SPSS 11.0 statistical analysis software, the cross-resistance was compared with Chi-square test. The difference was considered as statistical significance when P<0.05. Results Of 131 MDR-TB strains, the median of rifampin MICs was 256 μg/ml, and the median of rifabutin MICs was 2 μg/ml. The cross resistant rate between rifampin and rifabutin was 76.47%(91/119). In addition, 113 isolates(86.26%, 113/131) harbored rpoB mutations, in which there were 7 types of single mutations, including codon 531, 526, 516, 513, 511, 522, and 533, codon 531(56.50%, 74/131) and codon 526(16.03%, 21/131) were the most frequently observed. Besides, the mutations at codon 526 and 531 were associated with cross-resistance between rifampin and rifabutin, their cross-resistance rates were 90.48%(19/21) and 78.38%(58/74) respectively, which had no statistically significant difference（χ² were 9.641 and 8.223, P<0.05). Conclusion Rifabutin has cross-resistance with rifampin, but rifabutin showed better antimicrobial ability. The M. tuberculosis isolates with different rpoB mutations showed different cross-resistance between rifabutin and rifampin.

Key words: Mycobacterium tuberculosis, Drug resistance, multiple, bacterial, Rifabutin, Rifampin, Microbial sensitivity tests, Bacterial proteins

沈静，赵雁林，逄宇，张舜，杜昌廷，刘洁. 131株耐多药结核分枝杆菌对利福布丁与利福平交叉耐药的研究[J]. 中国防痨杂志, 2015, 37(4): 377-382. doi: 10.3969/j.issn.1000-6621.2015.04.010

SHEN Jing，ZHAO Yan-lin，PANG Yu，ZHANG Shun，DU Chang-ting，LIU Jie. Investigation of cross-resistance between rifampin and rifabutin in multidrug-resistant M.tuberculosis strains[J]. Chinese Journal of Antituberculosis, 2015, 37(4): 377-382. doi: 10.3969/j.issn.1000-6621.2015.04.010

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