Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
J Antimicrob Chemother. 2013 Jan;68(1):222-8. doi: 10.1093/jac/dks361. Epub 2012 Sep 14.
This prospective study was designed to compare the efficacies of levofloxacin-containing and high-dose metronidazole-containing quadruple therapies after failure of standard triple therapies.
A total of 150 Helicobacter pylori-infected patients were enrolled in our study and randomly assigned to levofloxacin-containing quadruple therapy (EBTL group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of levofloxacin once daily for 10 days) (n = 76) or high-dose metronidazole-based quadruple therapy (EBTM group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of metronidazole four times daily for 10 days) (n = 74). Follow-up endoscopy or urea breath test was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes and antibiotic resistances were also examined. All participants, caregivers and those assessing the outcomes were blinded to group assignment.
Intention-to-treat analysis revealed that both groups showed similar eradication rates: EBTL, 78.9% (60/76) (95% CI 69.7%-88.1%) and EBTM, 79.7% (59/74) (95% CI 70.5%-88.7%) [risk ratio (RR) 0.97, 95% CI 0.44-2.14]. Per-protocol results were EBTL = 87.0% (60/69) (95% CI 79.4%-94.9%) and EBTM = 90.8% (59/65) (95% CI 83.8%-97.8%) (RR 0.68, 95% CI 0.23-2.0). We did not find significant differences in compliance (RR 0.5, 95% CI 0.54-2.3) and adverse events (RR 1.11, 95% CI 0.54-2.3) between the two groups. Logistic regression analysis showed that only compliance was an important predictor for eradication failure. CYP2C19 polymorphism did not influence the eradicating effect.
The 10 day bismuth quadruple therapies with high-dose metronidazole or levofloxacin were effective even in areas with high resistance. These two therapies were equally safe and tolerated. Besides this, the metronidazole-containing therapy was cheaper. So it is persuasive that high-dose metronidazole-containing quadruple therapy could be a good choice for second-line H. pylori eradication in areas with high resistance.
本前瞻性研究旨在比较标准三联疗法失败后含左氧氟沙星和高剂量甲硝唑的四联疗法的疗效。
我们共纳入了 150 例幽门螺杆菌感染患者，并将其随机分配至含左氧氟沙星的四联疗法（EBTL 组）[埃索美拉唑 40 mg，每日 2 次；枸橼酸铋钾 300 mg，每日 4 次；四环素 500 mg，每日 4 次；左氧氟沙星 500 mg，每日 1 次，共 10 天]（n=76）或高剂量甲硝唑四联疗法（EBTM 组）[埃索美拉唑 40 mg，每日 2 次；枸橼酸铋钾 300 mg，每日 4 次；四环素 500 mg，每日 4 次；甲硝唑 500 mg，每日 4 次，共 10 天]（n=74）。16 周后进行内镜或尿素呼气试验以评估治疗反应。还检查了患者的反应、CYP2C19 基因型和抗生素耐药性。所有参与者、照料者和评估结果的人员均对分组情况不知情。
意向治疗分析显示，两组的根除率相似：EBTL 组为 78.9%（60/76）（95%CI 69.7%-88.1%），EBTM 组为 79.7%（59/74）（95%CI 70.5%-88.7%）[风险比（RR）0.97，95%CI 0.44-2.14]。根据方案治疗的结果为 EBTL 组=87.0%（60/69）（95%CI 79.4%-94.9%）和 EBTM 组=90.8%（59/65）（95%CI 83.8%-97.8%）（RR 0.68，95%CI 0.23-2.0）。我们未发现两组间在依从性（RR 0.5，95%CI 0.54-2.3）和不良事件（RR 1.11，95%CI 0.54-2.3）方面存在显著差异。逻辑回归分析显示，只有依从性是根除失败的重要预测因素。CYP2C19 多态性并未影响根除效果。
即使在耐药率较高的地区，10 天铋四联疗法联合高剂量甲硝唑或左氧氟沙星均有效。这两种疗法均安全且可耐受。此外，甲硝唑四联疗法更便宜。因此，高剂量甲硝唑四联疗法可作为耐药率较高地区二线幽门螺杆菌根除的一种较好选择。
