含铋剂和克拉霉素的四联根除方案在幽门螺杆菌一线治疗中的作用

背景：近年经典三联方案对幽门螺杆菌（H.pylori）感染的根除疗效明显下降,建立新型、安全和高效的一线标准治疗方案是临床工作的当务之急。目的：评估含铋剂和克拉霉素的四联方案作为H.pylori一线治疗方案的疗效和安全性。方法：120例胃镜诊断为非溃疡性消化不良的H.pylori感染患者随机分为3组：7 d三联组（奥美拉唑20 mgbid＋阿莫西林1000 mg bid＋克拉霉素500 mg bid,疗程7 d）、7 d四联组（7 d三联方案＋枸橼酸铋钾220 mg bid,疗程7 d）和2周四联组（方案同7 d四联组,疗程2周）。治疗结束后至少4周行13C-尿素呼气试验以评估根除疗效。H.pylori分离菌株行克拉霉素、甲硝唑和阿莫西林药敏试验。结果：115例患者按方案完成治疗。7 d三联组、7 d四联组和2周四联组按意向治疗（ITT）分析H.pylori根除率分别为70.0%、75.0%和90.0%,按方案（PP）分析分别为73.7%、76.9%和94.7%。2周四联组ITT和PP根除率均显著高于7 d三联组（P〈0.05）,PP根除率显著高于7 d四联组（P=0.026）,而7 d三联组ITT和PP根除率与7 d四联组相比均无明显差异。H.pylori对克拉霉素、甲硝唑和阿莫西林的耐药率分别为24.2%、48.3%和0%,7 d三联组、7 d四联组和2周四联组对克拉霉素耐药菌株的根除率逐渐升高（37.5%、55.6%、80.0%）,但差异无统计学意义。除2周四联组中1例患者因皮肤过敏而未完成治疗外,其余患者的不良反应相似且轻微,耐受性良好。结论：含铋剂和克拉霉素的2周四联方案可明显提高H.pylori根除疗效,且安全性较高,可作为H.pylori一线治疗的标准方案。

Evaluation of Bismuth-clarithromycin-containing Quadruple Therapy for Initial Helicobacter pylori Eradication

Background: Eradication rate of standard triple therapy for Helicobacter pylori(H.pylori) infection is decreasing recently.It is urgent to look for a novel,safe and effective regimen.Aims: To assess the efficacy and safety of bismuth-clarithromycin-containing quadruple regimen as a primary therapy for H.pylori eradication.Methods: A total of 120 H.pylori-infected patients with non-ulcer dyspepsia diagnosed by gastroscopy were enrolled and randomly assigned into three groups: 7-day triple therapy(omeprazole 20 mg bid,amoxicillin 1000 mg bid and clarithromycin 500 mg bid for 7 days),7-day quadruple therapy(7-day triple therapy plus bismuth potassium citrate 220 mg bid for 7 days) and 2-week quadruple therapy(7-day quadruple therapy for 2 weeks).At least four weeks after the end of treatment,H.pylori eradication was assessed by 13C-urea breath test.H.pylori strains isolated were tested for clarithromycin,metronidazole and amoxicillin resistance.Results: A total of 115 patients completed the study.H.pylori eradication rates by intention-to-treat(ITT) analysis in 7-day triple therapy,7-day quadruple therapy,2-week quadruple therapy were 70.0%,75.0%,90.0%,respectively;by per-protocol(PP) analysis were 73.7%,76.9%,94.7%,respectively.The eradication rate in 2-week quadruple therapy was significantly higher than that in 7-day triple therapy by both ITT and PP analysis(P<0.05),and was significantly higher than that in 7-day quadruple therapy by PP analysis(P=0.026).No significant difference in eradication rate by ITT and PP analysis was found between 7-day triple therapy and 7-day quadruple therapy.The resistance rates of H.pylori to clarithromycin,metronidazole and amoxicillin were 24.2%,48.3%,0%,respectively.The eradication rates of 7-day triple therapy,7-day quadruple therapy and 2-week quadruple therapy in patients with clarithromycin-resistant strains increased stepwisely(37.5%,55.6%,80.0%),but not reached statistical significance.Except one patient in 2-week quadruple therapy could not complete the course of treatment due to skin allergy,other patients in all three groups had slight and similar side-effects and all were well tolerated.Conclusions: Two-week bismuth-clarithromycin-containing quadruple therapy can increase the eradication rate of H.pylori with safety,and could be used as the first line eradication regimen.