幽门螺杆菌对左氧氟沙星耐药的研究  

Study on the Resistance of Levofloxacin to Helicobacter pylori

作　　者：梁晓[1] 刘文忠[1] 徐蔚文[1] 萧树东[1] 

机构地区：[1]上海交通大学医学院附属仁济医院消化内科上海市消化疾病研究所,200001

出　　处：《胃肠病学》2007年第10期589-592,共4页Chinese Journal of Gastroenterology

摘　　要：背景:耐药菌株的出现是近年来药物根除幽门螺杆菌(H.pylori)成功率下降的主要原因,尤其是对常用抗生素克拉霉素和甲硝唑耐药。左氧氟沙星是一个新近用于根除H.pylori的抗生素,含左氧氟沙星的方案是有效的补救方案,但关于左氧氟沙星的耐药率以及耐药机制目前知之甚少。目的:监测H.pylori对左氧氟沙星的耐药率,观察耐药倾向,探讨可能的耐药机制。方法:对2003年在仁济医院内镜中心行胃镜检查的连续26株临床菌株行左氧氟沙星、克拉霉素和甲硝唑敏感性试验;选取8株敏感株(2株标准菌株)行左氧氟沙星体外选择耐药试验:以修饰内切酶位点的指定引物人工将HinfⅠ酶切位点引入左氧氟沙星耐药菌株(体外人工选择分离株和临床株)的聚合酶链反应(PCR)产物,然后以HinfⅠ行酶切以鉴别gyrA基因91位密码子是否存在突变。结果:左氧氟沙星的耐药率为3.8% (1/26),2株对克拉霉素耐药的菌株均对左氧氟沙星敏感。体外选择耐药试验的8侏菌株中有5株选择分离出耐药菌株,但均为低度耐药菌株。4株体外人工选择分离耐药菌株均为gvrA基因喹诺酮耐药决定区域(QRDR)中编码Asp91的密码子突变,5株临床耐药株中有4株为91位密码子突变。结论:目前H.pylori对左氧氟沙星的耐药率低,左氧氟沙星是较好的根除H.pylori方案的可选药物之一。由于体外试验较易选择出耐药,因此需监测左氧氟沙星的耐药率。gyrA基因QRDR中编码91位Asp的密码子突变在左氧氟沙星的耐药机制中占主导地位。Background：The emergence of resistant strains of Helicobacter pylori （H. pylori） is the main cause of lowering of eradication rate, especially of the commonly used antibiotics such as clarithromycin and metronidazole. Levofloxacin is an antibiotic recently used in the rescue therapy for H. pylori infection, but its resistance rate and mechanism of resistance are unknown. Aims： To investigate the resistance rate and tendency of H. pflori to levofloxacin and its possible mechanism. Methods： Agar dilution tests detecting the minimum inhibitor7 concentration （MIC） for levofloxacin, clarithromycin and metronidazole were performed in 26 clinical H. pylori strains isolated consecutively in 2003. Resistance selection test in vitro was performed in 8 levofloxacin sensitive strains of H. pylori （2 standard strains and 6 clinical strains）. Hinf Ⅰ site was introduced into the polymerase chain reaction （PCR） product of levofloxacin resistant strains （in vitro selected strains and clinical isolated strains）, and then Hinf Ⅰ digestion was used to determine whether there was a mutation of codon 91 in gyrA gene. Results： The resistance rate of H. pylori to levofloxacin was 3.8% （1/26）, all 2 strains of H. pylori resistant to clarithromycin were sensitive to levofloxacin. Resistant strains to levofloxacin were isolated in 5 of the 8 strains undergoing resistance selection test, but all were of low-level resistance. Four resistant strains isolated in the resistance selection test in vitro and 4 of the 5 clinical resistant strains had mutation in codon 91 of quinolone resistancedetermining region （QRDR） in gyrA gene. Conclusions： Because of its low resistance rate, levofloxacin is currently a good alternative to be used in eradication therapy. Considering resistant strains could be selected in vitro, monitoring its occurrence and rate of resistance are important. Mutation in codon 91 in the QRDR of gyrA gene plays an important role in the development of levofloxacin resistance.

关 键 词：螺杆菌 幽门 抗药性 氧氟沙星 DNA促旋酶 

分 类 号：R446.5[医药卫生—诊断学] R450[医药卫生—临床医学]