结核分枝杆菌耐利福平基因变异株的体外最小抑菌浓度研究

目的：研究结核分枝杆菌（MTB）耐利福平临床分离株基因突变对其体外最小抑菌浓度（MIC）测定结果的影响。方法用基因芯片对临床分离的对利福平耐药的175株 MTB及对利福平敏感的48株 MTB进行耐药基因检测；并对所有标本进行利福平的 MIC测定，比较不同变异株的 MIC测定结果。结果对利福平耐药的 MTB 临床分离株基因突变以531、526、516、533位点单突变为主；531位点单突变的利福平耐药变异株 MIC 高于526位点单突变的耐药变异株，差异有统计学意义（t′＝2．2237，t′α＝2．0449，P＜0．05）；526位点单突变的利福平耐药变异株 MIC高于516位点单突变的耐药变异株，差异有统计学意义（t＝2．2056，P＝0．0329，P＜0．05）。双突变者均有较高的 MIC测定值。结论合理的基因芯片设计能检出95．0％以上的对利福平耐药 MTB变异株；对利福平耐药的 MTB变异株有不同的基因突变模式，且不同突变模式的 MTB耐药程度不同，可以为临床用药提供参考。

In vitro minimal inhibitory concentration determination of Mycobacterium tuberculosis rifampin resistant gene mutants

Objective To study gene mutations of rifampin-resistant Mycobacterium tuberculosis strains in clinical isolated sam- pies,and their influence on minimal inhibitory concentration （MIC） determination in vitro. Methods Rifampin resistant genes of 175 Mycobacterium tuberculosis rifampin-resistant strains and 40 rifampin-sensitive strains in clinical isolated were detected by gene chip technology,and the MICs on rifampin were determined in all these selected samples,and compared with MIC results from dif- ferent gene mutations. Results Gene mutation sites of rifampin-resistant Mycobacteriurn tuberculosis strains from clinical isolated mainly included 531,526 and 516,533;The MIC of single 531 site mutation in rifampin-resistant strains was higher than single 526, t＇=2. 223 7,t＇α=2. 0449,P〈0.05;The MIC of single 526 site mutation in RFP resistant strains was higher than single 516,t= 2. 205 6,P=0. 032 9,P〈0.05. Combined mutation induced higher MICs. Conclusion The reasonable gene chip design can detect over 95 % rifampin-resistant genes. Mutation patterns of genes have significant influence on the resistance, which provides an impor- tant reference to the clinic.