The HOMER study:: The effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection
The HOMER study:: The effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection
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DOI：
10.1046/j.1523-5378.2000.00030.x
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发表时间：
2000-12-01
期刊：
影响因子：
4.4
通讯作者：
Zeijlon, L
中科院分区：
文献类型：
--
作者：
Bardhan, KD;Bayerdörffer, E;Zeijlon, L
背景资料。使用奥美拉唑、阿莫西林和甲硝唑根除幽门螺杆菌既有效又便宜。然而，不同剂量和剂量的根治率不同，关于耐药性影响的数据很少。本研究比较了3种不同剂量的奥美拉唑、阿莫西林和甲硝唑，并分析了甲硝唑耐药性对根除的影响。在4个欧洲国家和加拿大进行的一项多中心研究中，394名幽门螺杆菌筛查阳性且有十二指肠溃疡内窥镜检查结果的患者被纳入研究。在基线内窥镜检查后，患者被随机分配到治疗一周：奥美拉唑每天两次20毫克，阿莫西林每天两次1,000毫克，甲硝唑每天两次400毫克(低M)；奥美拉唑每天40毫克，阿莫西林每天3次500毫克，甲硝唑每天三次400毫克(中M)；或奥美拉唑每天两次20毫克，阿莫西林每天两次1000毫克，甲硝唑每天两次800毫克(中M)。通过C-13尿素呼气试验和培养来评估进入时的幽门螺杆菌状况。根除定义为治疗后4周和8周两次C-13-尿素呼气试验结果阴性。用琼脂稀释法对入院时和治疗后持续感染的患者进行药敏试验。根据治疗意向(ITT)(人口n=379)(95%可信区间[CI])，根治率如下：低M76%(68%，84%)，中M76%(68%，84%)，高M83%(75%，89%)。按方案分析(人口n=348)，低M81%、中M80%、高M85%。未发现幽门螺杆菌对阿莫西林耐药。研究前，在348个国家的培养物中，有72个(21%)发现幽门螺杆菌对甲硝唑耐药(在这五个国家中，范围为10%-39%)。在研究前的266株甲硝唑敏感株中，总的根治率为232株(87%)，而对于70株耐药株，总的根治率为41株(57%；P<；001)。在每一组内，结果如下(敏感/耐药)：低M，85%/54%；中M，86%/50%；高M，90%/75%。各治疗组间差异无统计学意义。23株治疗前对甲硝唑敏感的菌株在治疗失败后重新培养，其中20株现已产生耐药性。三种方案的幽门螺杆菌根治率相似(约80%)。甲硝唑耐药性降低了疗效；增加甲硝唑剂量似乎不能克服这个问题，也不能显著改善结果。治疗失败通常与研究前或获得性甲硝唑耐药有关。这些发现对于在甲硝唑耐药水平较高的社区尝试根除幽门螺杆菌具有重要意义。
Background. Helicobacter pylori eradication with omeprazole, amoxicillin, and metronidazole is both effective and inexpensive. However, eradication rates with different dosages and dosing vary, and data on the impact of resistance are sparse. In this study, three different dosages of omeprazole, amoxicillin, and metronidazole were compared, and the influence of metronidazole resistance on eradication was assessed.Methods. Patients (n = 394) with a positive H. pylori screening test result and endoscopy-proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada. After baseline endoscopy, patients were randomly assigned to treatment for 1 week with either omeprazole, 20 mg twice daily, plus amoxicillin, 1,000 mg twice daily, plus metronidazole, 400 mg twice daily (low M); or omeprazole, 40 mg once daily, plus amoxicillin, 500 mg three times daily, plus metronidazole, 400 mg three times daily (medium M); or omeprazole, 20 mg twice daily, plus amoxicillin, 1,000 mg twice daily, plus metronidazole, 800 mg twice daily (high M). H. pylori status at entry was assessed by a C-13 urea breath test and a culture. Eradication was defined as two negative C-13-urea breath test results 4 and 8 weeks after therapy. Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy.Results. The eradication rates, in terms of intention to treat (ITT) (population n = 379) (and 95% confidence interval [CI]) were as follows: low M 76% (68%, 84%), medium M 76% (68%, 84%), and high M 83% (75%, 89%). By per-protocol analysis (population n = 348), the corresponding eradication rates were: low M 81%, medium M 80%, and high M 85%. No H. pylori strains were found to be resistant to amoxicillin. Prestudy resistance of H. pylori strains to metronidazole was found in 72 of 348 (21%) of the cultures at entry (range, 10%-39% in the five countries). The overall eradication rate in prestudy metronidazole-susceptible strains was 232 of 266 (87%) and, for resistant strains, it was 41 of 70 (57%; P < 001). Within each group, the results were as follows (susceptible/resistant): low M, 85%/54%; medium M, 86%/50%; and high M, 90%/75%. There were no statistically significant differences among the treatment groups. 23 strains susceptible to metronidazole before treatment were recultured after therapy failed; 20 of these had now developed resistance.Conclusions. H. pylori eradication rates were similar (approximately 80%) with all three regimens. Metronidazole resistance reduced efficacy; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome. Treatment failure was generally associated with either prestudy or acquired metronidazole resistance. These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance.