中国幽门螺杆菌耐药状况以及耐药对治疗的影响—全国多中心临床研究

Prevalence of Helicobacter pylori Resistance to Antibiotics and its Influence on the Treatment Outcome in China:A Multicenter Clinical Study

背景:随着幽门螺杆菌(H.pylori)根除治疗的广泛开展,H.pylori对抗生素的耐药率逐年上升,并成为含质子泵抑制剂(PPI)三联疗法根除率下降的主要原因。了解我国H.pylori对抗生素的总体耐药情况,对指导我国临床医师开展H.pylori根除治疗有重要参考价值。目前这方面的资料尚少。目的:了解我国H.pylori对抗生素(甲硝唑、克拉霉素和阿莫西林)的耐药情况以及耐药对三联7d疗法根除H.pylori治疗的影响。方法:采用全国多中心随机对照临床研究。共纳入910例因上消化道症状而接受胃镜检查的H.pylori感染者,所有患者随机分为两个治疗组:LCA组,兰索拉唑30 mg bid,克拉霉素500 mg bid,阿莫西林1000 mg bid;LCM组,兰索拉唑30 mg bid,克拉霉素500 mg bid,甲硝唑400 mg bid。疗程均为7 d,均行H.pylori培养。H.pylori分离菌株采用E-test法行甲硝唑、克拉霉素和阿莫西林药敏实验,甲硝唑最低抑菌浓度(MIC)≥8 mg/L、克拉霉素MIC≥2 mg/L、阿莫西林MIC≥1 mg/L判断为耐药。结果:910例患者中,LCA组和LCM组的H.pylori按方案(PP)分析根除率分别为82.7%和68.6%(P<0.001)。340例H.pylori菌株培养阳性。H.pylori对甲硝唑、克拉霉素和阿莫西林的耐药率分别为75.6%、27.6%和2.7%。LCM组对甲硝唑和克拉霉素均敏感和均耐药菌株的PP根除率分别为84.4%和42.1%(P<0.001)。LCA组对克拉霉素敏感和耐药菌株的PP根除率分别为91.6%和58.1%(P<0.001)。结论:中国H.pylori菌株对甲硝唑和克拉霉素的耐药率均较高,对阿莫西林的耐药率较低。H.prlori对抗生素耐药是导致根除治疗失败的主要原因。

Background： The increase in resistance to antibiotics emerged as a significant clinical problem seems to result in a decrease in the efficacy of Helicobacter pylori （ H. pylori ） eradication therapy in recent years. The information about H. pylori resistance status to antibiotics in China has not been very clear, but is important for improving the efficacy by establishing a reasonable first-line therapy. Aims： To investigate the prevalence of H. pylori resistance to metronidazole, clarithromycin and amoxicillin in China and to evaluate the effect of H. pylori resistance to antibiotics on the cure rates of anti-H, pylori 7-day triple therapies. Methods： Sixteen medical centers joined this muhicenter randomized trial. Nine hundreds and ten H. pylori infected patients with upper abdominal symptoms referred for gastroendoscopy were enrolled. Patients were randomized into 2 groups： Group LCA （lansoprazole 30 mg bid, clarithromycin 500 mg bid, amoxicillin 1000 mg bid, for 7days） and Group LCM （lansoprazole 30 mg bid, clarithromycin 500 mg bid, metronidazole 400 mg bid, for 7 days）. H. pylori was cultured from gastric biopsy specimens and the isolated strains were tested for metronidazole, clarithromycin and amoxicillin resistance by E-test. Minimum inhibitory concentration （MIC） ≥8 mg/L for metronidazole, ≥ 2 mg/L for clarithromycin and ≥ 1 mg/L for amoxicillin were considered resistant. Results： The per protocol （PP） eradication rates of H. pylori were 82.7% for LCA group and 68.6% for LCM group （P〈0.001）, respectively. H. pylori strains were cultured from gastric biopsy specimens obtained from 340 patients among the 910 patients. The resistance rates were 75.6% for metronidazole, 27.6% for clarithromycin and 2.7% for amoxicillin. In group LCM, the PP eradication rates in patients with strains sensitive to both metronidazole and clarithromycin, and strains resistant to both metronidazole and clarithromycin were 84.4% and 42.1% （P〈0.001）, respectively. The PP eradication rates in patients with strains sensitive to clarithromycin and resistant to clarithromycin in group LCA were 91.6% and 58.1% （P〈0.001）, respectively. Conclusions： The resistance rates of H. pylori to metronidazole and clarithromycin are high and the resistance rate to amoxicillin is relatively low in China. It suggests that resistance to metronidazole and clarithromycin is the main cause of failure of eradication therapy for H. pylori infection.