Hsu Chia-Chang, Chen Jyh-Jou, Hu Tsung-Hui, Lu Sheng-Nan, Changchien Chi-Sin
Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical Center Chang Gung Memorial Hospital, Tainan, Taiwan.
Hepatogastroenterology. 2005 Sep-Oct;52(65):1617-21.
BACKGROUND/AIMS: Eradication regimens combining two antibiotics with a proton pump inhibitor have been studied intensively in Helicobacter pylori (H. pylori) infection; however, only a few reports have focused on the role of H2-receptor antagonists (H2-RAs) in eradication therapy. The mechanism involved in the synergy between antibiotics and H2RAs are still elusive. So we compared the efficacy of two regimens: a 1-week or 2-week course of high-dose H2-RA-based triple therapy in patients with H. pylori infection, and assessed the impact of primary resistance for metronidazole on the treatment outcome.
One hundred and twenty patients with peptic ulcers and nonulcer dyspepsia were randomly assigned to a one-week course of famotidine 40mg b.i.d., amoxicillin lg b.i.d. and tinidazole 500 mg b.i.d. (FAT1 group; n = 60) or a 2-week course of famotidine 40 mg b.i.d., amoxicillin lg b.i.d. and tinidazole 500 mg b.i.d. (FAT2 group; n = 60). Upper endoscopy was performed prior to treatment and at least 4 weeks after completion of treatment and discontinuation of the antisecretory therapy. H. pylori status was assessed by biopsy urease test, histology and culture.
In the intention-to-treat analysis, eradication of H. pylori was achieved in 38 of 60 patients (63.3%; 95% CI: 51-76%) in the FAT1 group, compared to 48 of 60 patients (80%; 95% CI: 70-92%) in the FAT2 group (NS). In the per protocol analysis, eradication therapy was achieved in 38 of 54 patients (70.4%; 95% CI: 58-82%) in the FAT1 group and 48 of 53 patients (90.6%; 95% CI: 83-98%) in the FAT2 group (p < 0.05). The overall eradication rates for strains susceptible and resistant to metronidazole were 79.7% (95% CI: 71-89%) vs. 60% (95% CI: 44-74%) in the intention-to-treat analysis (p = 0.016) and 84% (95% CI: 76-92%) vs. 71.9% (95% CI: 56-88%) in the per protocol analysis (p = 0.12). Seven patients in the FAT1 group and six patients in the FAT2 group available for follow-up reported adverse events (11.7% and 10% respectively) without necessity of discontinuation of the study medications. Serious adverse events were not observed.
A 2-week course of high-dose H2-RA-based triple therapy is well tolerated and sufficiently effective in eradicating H. pylori infection. Presence of metronidazole resistance has a negative impact on the treatment efficacy.
背景/目的：含两种抗生素与一种质子泵抑制剂的根除方案已在幽门螺杆菌（H. pylori）感染中得到深入研究；然而，仅有少数报告关注H2受体拮抗剂（H2-RAs）在根除治疗中的作用。抗生素与H2-RAs协同作用的机制仍不清楚。因此，我们比较了两种方案的疗效：以高剂量H2-RA为基础的三联疗法，疗程为1周或2周，用于治疗幽门螺杆菌感染患者，并评估甲硝唑原发耐药对治疗结果的影响。
120例消化性溃疡和非溃疡性消化不良患者被随机分为法莫替丁40mg每日2次、阿莫西林1g每日2次和替硝唑500mg每日2次的1周疗程组（FAT1组；n = 60）或法莫替丁40mg每日2次、阿莫西林1g每日2次和替硝唑500mg每日2次的2周疗程组（FAT2组；n = 60）。在治疗前以及治疗结束并停用抗分泌治疗至少4周后进行上消化道内镜检查。通过活检尿素酶试验、组织学和培养评估幽门螺杆菌状态。
在意向性分析中，FAT1组60例患者中有38例（63.3%；95%CI：51 - 76%）实现了幽门螺杆菌根除，而FAT2组60例患者中有48例（80%；95%CI：70 - 92%）（无显著性差异）。在符合方案分析中，FAT1组54例患者中有38例（70.4%；95%CI：58 - 82%）实现了根除治疗，FAT2组53例患者中有48例（90.6%；95%CI：83 - 98%）（p < 0.05）。在意向性分析中，对甲硝唑敏感和耐药菌株的总体根除率分别为79.7%（95%CI：71 - 89%）和60%（95%CI：44 - 74%）（p = 0.016），在符合方案分析中分别为84%（95%CI：76 - 92%）和71.9%（95%CI：56 - 88%）（p = 0.12）。FAT1组7例和FAT2组6例可进行随访的患者报告了不良事件（分别为11.7%和10%），无需停用研究药物。未观察到严重不良事件。
以高剂量H2-RA为基础的2周疗程三联疗法耐受性良好，在根除幽门螺杆菌感染方面足够有效。甲硝唑耐药的存在对治疗疗效有负面影响。
