二联方案在幽门螺杆菌根除治疗中的应用进展

幽门螺杆菌(Helicobacter pylori,H.pylori)在世界范围内感染率高,随着H.pylori对常用抗生素的耐药率逐渐增加,高效的经验性治疗方案亟待探索。新近Maastricht V/Florence共识及我国第五次幽门螺杆菌感染处理共识均推荐含铋剂四联方案可作为一线治疗方案。但是,四联方案存在用药多、药物不良反应多、患者依从性差、部分老年人及肝、肾功能不全的患者无法耐受等缺点。近年来多项研究显示高剂量阿莫西林联合质子泵抑制剂(proton pump inhibitor,PPI)的二联方案与含铋剂四联方案的疗效相近,但用药少,不良反应少,患者依从性更高,有可能成为经验性的一线治疗方案,或成为一线、二线治疗失败后的补救方案。本文就二联方案在H.pylori根除治疗中的应用进展作一综述。     

铋剂四联疗法联合不同药物对 幽门螺杆菌感染的疗效

目的分析铋剂四联疗法联合不同药物对幽门螺杆菌感染的疗效。方法入选患者依据治疗方案不同进行分组,其中A组患者采用铋剂四联方案(1种PPI+1种铋剂+2种抗生素)进行治疗,B组患者采用铋剂四联+思联康治疗,C组患者采用铋剂四联+荆花胃康治疗。3组患者均于根除治疗结束停药1个月后复查~(13)C呼气试验以评估疗效。对各方案的H.pylori根除率进行评比,并分析其临床疗效和成本-效益情况。结果按ITT集分析时,C组与A组患者根除率比较差异无统计学意义(χ~2=3.642,P=0.056),B组与A组和C组患者比较差异无统计学意义(χ~2=3.209、0.130,P0.05)。按PP集分析时,C组患者根除率最高,A组患者根除率最低,B、C组与A组患者比较差异有统计学意义(χ~2=4.620、4.419,P0.05),B、C两组根除率比较差异无统计学意义(χ~2=0.062,P0.05)。A组、B组和C组患者不良反应发生率按PP集计算分别为50.0%、7.9%和26.7%,3组患者不良反应发生率两两比较差异均有统计学意义(均P0.05)。成本-效益分析结果显示B组患者的成本-效果比值最小。结论综合有效性、安全性及成本-效益比分析,铋剂四联+思联康方案具有H.pylori根除率高,患者不良反应发生率低,成本效益比低的优势,提示此方案为本研究的最佳方案,值得临床推广应用。     

金双歧联合含左氧氟沙星和铋剂的四联疗法根除幽门螺杆菌的疗效观察

目的比较金双歧联合含左氧氟沙星和铋剂四联疗法根除幽门螺旋杆菌(Helicobacter pylori,H.pylori)的疗效。方法纳入180例H.pylori感染患者,随机分为3组:A组给予雷贝拉唑、阿莫西林、克拉霉素、胶体果胶铋治疗;B组给予雷贝拉唑、阿莫西林、左氧氟沙星、胶体果胶铋治疗;C组给予雷贝拉唑、阿莫西林、左氧氟沙星、胶体果胶铋、金双歧治疗。疗程10d。观察各组H.pylori根除率、药物不良反应发生率。结果H.pylori根除率B组(83.3%)和C组(90.0%)高于A组(70.0%),差异有统计学意义(P0.05);C组(90.0%)高于B组(83.3%),差异有统计学意义(P0.05)。不良反应发生率A组(31.7%)和B组(30.0%)高于C组(10.0%),差异有统计学意义(P0.05);A组(31.7%)高于B组(30.0%),但差异无统计学意义(P0.05)。结论金双歧联合含铋剂四联疗法根除幽门螺杆菌疗效肯定,不良反应小,值得临床推广。     

布拉氏酵母菌散剂联合三联疗法对 儿童幽门螺杆菌感染的治疗

目的观察布拉氏酵母菌散剂联合以质子泵抑制剂(PPI)为基础的标准三联疗法对儿童幽门螺杆菌(H.pylori)感染的疗效,以探索根除率高且不良反应少的H.pylori根除方案。方法采用前瞻性随机对照研究,从确诊为H.pylori感染的患儿中选取120例作为研究对象,再随机分为布拉氏组和标准三联疗法组,每组各60例。标准三联疗法组口服阿莫西林[50mg/(kg·d),饭后分两次服]、克拉霉素[20mg/(kg·d),饭后分两次服]和奥美拉唑[0.7～0.8mg/(kg·d),饭前半小时一次服完]治疗,布拉氏组在标准三联疗法的基础上加服布拉氏酵母菌散剂(250mg/次,2次/d)。两组患者均治疗14d,由患儿家属记录治疗过程中发生不良反应的情况。停药后4周内不再口服任何抗生素,后行14 C呼气试验以评估H.pylori根除情况。比较两组患者根除率及不良反应发生率。结果治疗后三联疗法组H.pylori根除率为76.7%(46/60),布拉氏组为90.0%(54/60),二者差异有统计学意义(P0.05)。治疗过程中布拉氏组患者腹泻发生率低于三联疗法组,差异有统计学意义(P0.05)。结论布拉酵母联合三联疗法能提高H.pylori的根除率,降低治疗过程中的不良反应。     

益生菌四联疗法对比铋剂四联疗法根除幽门螺杆菌感染的Meta分析

目的系统评价益生菌四联疗法对比铋剂四联疗法根除幽门螺杆菌(H.pylori)感染的疗效和不良反应。方法计算机检索中英文数据库,收集上述2种方案根除H.pylori感染的随机对照试验(RCT),检索时间均从建库至2016年10月。由2名评价员独立筛选文献、提取资料、评价纳入研究的偏倚风险,采取RevMan 5.3软件进行Meta分析。结果最终纳入12个RCT(共1 687例患者)。Meta分析结果显示:益生菌四联组患者对比铋剂四联组的H.pylori根除率按ITT分析为:80.6%vs81.2%;按PP分析为:81.2%vs 83.7%,差异无统计学意义(ITT分析:RR=0.99,95%CI:0.95~1.04,P=0.76;PP分析:RR=0.97,95%CI:0.93~1.01,P=0.17);益生菌四联组的总不良反应的发生率明显低于对照组(16.0%vs 34.9%),且差异有统计学意义(RR=0.46,95%CI:0.37~0.57,P0.01)。结论现有证据显示,益生菌四联疗法与铋剂四联疗法的H.pylori根除率相当,但益生菌四联疗法的不良反应低于铋剂四联疗法。由于纳入研究数量有限,质量不高,上述结论有待高质量的研究予以验证。     

铋剂四联疗法联合双岐三联活菌对Hp感染患者的疗效

为了对比分析2种含铋剂四联疗法联合双岐三联活菌胶囊分别对幽门螺杆菌(Helicobacter pylori,Hp)感染患者疗效的影响。本研究随机选取200例就诊的Hp感染患者,将患者随机分为4组,每组50例。A组(埃索美拉唑,克拉霉素,阿莫西林,枸橼酸铋钾胶囊)、B组(埃索美拉唑,呋喃唑酮,阿莫西林,枸橼酸铋钾胶囊)、C组(埃索美拉唑,克拉霉素,阿莫西林,枸橼酸铋钾胶囊,双歧杆菌三联活菌胶囊)和D组(埃索美拉唑,呋喃唑酮,阿莫西林,枸橼酸铋钾胶囊和双歧杆菌三联活菌胶囊)。分析对比四组患者的临床缓解疗效、幽门螺旋杆菌根除效率、不良反应、复发情况及成本效果比。研究表明:2种含铋剂四联疗法联合双岐三联活菌胶囊对幽门螺杆菌感染患者的临床缓解症状、幽门螺杆菌根除率效果、不良反应发生率和复发情况效果优于含铋剂四联疗法,但是D组成本效果比更具有经济学优势。埃索美拉唑、呋喃唑酮、阿莫西林、枸橼酸铋钾胶囊和双歧杆菌三联活菌胶囊联合可促进Hp患者恢复,根除率高,降低不良反应和复发率,且具有经济学优势,值得推广应用。     

标准四联法对幽门螺旋杆菌相关性消化道溃疡的临床研究

目的观察标准四联对幽门螺旋杆菌(Helicobacter pylori,H.pylori)相关性消化道溃疡的临床效果和安全性。方法选取我院2013年5月至2014年6月收治的H.pylori相关性消化道溃疡患者160例,按照随机数字法随机分为观察组和对照组,每组80例。观察组采用兰索拉唑、阿莫西林、克拉霉素联合胶体果胶铋的标准四联法治疗;对照组采用兰索拉唑、阿莫西林、克拉霉素标准三联法治疗,对比分析两组临床症状缓解率、溃疡愈合率、H.pylori根除率及不良反应情况。结果两组治疗1周的临床症状缓解率相比差异无统计学意义(χ2=2.064,P0.05);治疗4周后观察组的临床症状缓解率为96.25%,显著性高于对照组的81.25%(χ2=9.014,P0.05)。观察组溃疡愈合率为88.75%,显著性高于对照组的77.5%(χ2=4.449,P0.05);观察组H.pylori根除率为91.25%,显著性高于对照组的76.25%(χ2=6.613,P0.05)。两组治疗期间均未发现肝肾功能异常及其他严重不良反应;两组不良反应发生率相比差异无统计学意义(χ2=0.278,P0.05)。结论标准四联对H.pylori相关性消化道溃疡的临床症状缓解率高、H.pylori根除率高、溃疡愈合率高,安全性高,值得临床推广。     

益生菌联合抗幽门螺杆菌治疗对 消化性溃疡患者的疗效

目的探讨益生菌联合抗幽门螺杆菌(H.pylori)治疗对消化性溃疡患者的疗效及其对患者肠道菌群的影响。方法将120例经14 C呼气试验(14 C-UBT)检测确定为H.pylori感染阳性的消化性溃疡患者随机分为观察组和对照组,每组60例。其中,对照组采用四联疗法(奥美拉唑+阿莫西林+克拉霉素+铋剂)治疗,观察组采用四联疗法联合益生菌治疗;比较两组患者H.pylori根除情况、溃疡愈合质量及不良反应情况。治疗前后留取全部患者的新鲜粪便标本进行细菌培养,比较两组患者肠道菌群数量和肠道微生物定植抗力(B/E值)。结果观察组患者H.pylori根除率和溃疡愈合率分别为88.3%、95.0%,显著高于对照组的70.0%和76.7%(P0.05),不良反应率为3.3%,显著低于对照组的20.0%(P0.05)。与治疗前比,对照组患者治疗后肠道内产气荚膜梭菌、双歧杆菌及乳杆菌数量显著减少(P0.05),肠杆菌、肠球菌及酵母菌数量显著增加(P0.05),B/E值显著降低(P0.05);观察组患者治疗后双歧杆菌和乳杆菌数量均显著增加(P0.05),产气荚膜梭菌数量显著减少(P0.05),肠杆菌、肠球菌及酵母菌数量无明显变化(P0.05),B/E值显著升高(P0.05)。结论常规抗H.pylori治疗易引起消化性溃疡患者肠道菌群紊乱,降低肠道定植抗力。益生菌联合治疗可有效改善患者肠道微生态,提高H.pylori根除率和溃疡愈合质量,减少不良反应。     

益生菌在幽门螺杆菌根除治疗中的应用

幽门螺杆菌(Helicobacter pylori,H.pylori)是导致活动性胃炎、消化性溃疡、胃癌、胃黏膜相关淋巴组织淋巴瘤等消化系统疾病的重要病因之一,已被世界卫生组织确认为Ⅰ类致癌因子,根除H.pylori对防治上述疾病有重要意义。目前临床上主要采用含抗生素的三联或四联药物进行H.pylori的根除,虽然取得一定的疗效,但随着抗生素耐药率逐年增加,根除率持续下降,限制了其广泛应用。此外,初次或多次治疗失败后再治疗可选择的药物很少。近年来人们开始尝试将益生菌应用在H.pylori根除治疗中,并取得一定疗效。本文就益生菌在辅助根除幽门螺杆菌方面的研究进展作一简单综述。     

益生菌联合标准四联疗法对幽门螺杆菌感染再次治疗的疗效及其对炎症因子的影响

目的 研究布拉酵母菌联合标准四联疗法对幽门螺杆菌(H.pylori)感染患者再次治疗的疗效及其对炎症因子的影响。方法 选取我院124例H.pylori感染患者,按随机分配的方法分为A组和B组,每组62例。A组患者给予阿莫西林胶囊1 000 mg/次,2次/d;呋喃唑酮100 mg/次,2次/d;雷贝拉唑40 mg/次,2次/d;胶体果胶铋干混悬剂150 mg/次,4次/d,疗程14 d。B组患者在A组治疗方案的基础上加用布拉酵母菌250 mg/次,3次/d,疗程14 d。在治疗过程中观察患者的不良反应发生情况。疗程结束完全停药4周后检测两组患者H.pylori根除及症状改善情况。对比治疗前后患者血清白介素-6(IL-6)、肿瘤坏死因子(TNF-α)、C-反应蛋白(CRP)水平。结果 观察组患者H.pylori的根除率、症状改善率和不良反应的发生率与对照组相比差异均有统计学意义(χ²=7.322、9.239、10.016,均P<0.05)。治疗后观察组患者血清IL-6、TNF-α、CRP水平较对照组降低(t=9.780、8.495、7.002,均P<0....     

Treatment of Helicobacter pylori Infection

Antibiotic resistance has resulted in unsatisfactory eradication results with dual and now triple therapy in many countries. Newer antibiotics and changes in dosing and duration of therapy may overcome resistant strains but may only provide limited improvement in eradication rates. Sequential therapy with amoxicillin (1 g twice a day) and a proton pump inhibitor (PPI) (twice a day) given for 5 days followed by a PPI plus clarithromycin (500 mg twice a day) and tinidazole (500 mg twice a day) for 5 days is now a first-line therapy for Helicobacter pylori in some countries. Standard triple therapy is effective in regions where clarithromycin resistance is low. Levofloxacin based triple therapy is an effective alternative to quadruple therapy in second-line treatment. Adjuvant therapy may reduce side-effects and improve compliance. Molecular and genomic research on H. pylori may result in the development of targeted antibiotic therapy; however, more research is required in this field. Further research in vaccination is also necessary before this can become an option in clinical practice.     

Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an excellent cure rate with five-day therapy

Background. New triple therapy for eradication of Helicobacter pylori based on a proton pump inhibitor (PPI) provides a cure rate of approximately 90% with few adverse effects. Recently, a PPI-based quadruple therapy, which consists of a PPI plus bismuth-based triple therapy for 7 days, has been studied, and a sufficient eradication rate has been achieved. However, a shorter duration results in improved compliance. In this study, newly developed short-term, simple twice-daily quadruple therapy consisting of rabeprazole, amoxicillin, clarithromycin, and metronidazole (RACM) was compared with a PPI-based triple-therapy regimen for eradication of H. pylori.
Patients and Methods. This study was designed as a randomized open, prospective single-center study. Of a total of 105 H. pylori –positive patients, 55 received the RACM regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; clarithromycin, 200 mg bid; and metronidazole, 250 mg bid), and 50 received the RAC regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; and clarithromycin, 200 mg bid). Cure of the infection was assessed by HpSA ( H. pylori stool antigen immunoassay) 1 month after completion of therapy.
Results. The rates of eradication of H. pylori by RACM versus RAC were 94.5% (95% CI, 85–99) versus 80.0% (95% CI, 66–90) by intention-to-treat analysis; 98.1% (95% CI, 90–100) versus 87.0% (95% CI, 74–95) by all-patients-treated analysis; and 98.1% (95% CI, 90–100) versus 86.7% (95% CI, 73–95) by per-protocol analysis. No major adverse effects were reported, and 98.0% of patients reported complete compliance.
Conclusions. The simple twice-daily and short-term quadruple regimen for only 5 days provided an excellent eradication rate. Compliance with the regimen was high, and serious adverse effects were few. Therefore, the RACM regimen can be considered as safe and effective.     

Impact of furazolidone-based quadruple therapy for eradication of Helicobacter pylori after previous treatment failures

Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third‐line (salvage) therapy. Methods. All patients with previous H. pylori treatment failure after a clarithromycin‐metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI‐B‐T‐M) three times a day (tid) for 1 week. In the case of treatment failure with this second‐line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI‐B‐T‐F) instead of metronidazole (sequential study design). Results. Eighteen consecutive patients were treated with PPI‐B‐T‐M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI‐B‐T‐F. Final cure of H. pylori with PPI‐B‐T‐F was achieved in 9/10 patients (90%) nonresponsive to PPI‐B‐T‐M. Conclusions. In the presence of metronidazole resistance, PPI‐B‐T‐M as a recommended second‐line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second‐line quadruple therapy may be best suited in case of a metronidazole‐free first line‐regimen (e.g. PPI‐clarithromycin‐amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI‐B‐T‐F combination does not have a cross‐resistance potential to metronidazole and is a promising salvage option after a failed PPI‐B‐T‐M regimen.     

Twice-a-day quadruple therapy for eradication of Helicobacter pylori in the elderly

BACKGROUND: Midday and evening twice-a-day quadruple therapy appears to be the most effective therapy for Helicobacter pylori infection in Northern Sardinia, a site where antibiotics resistance is common. Aim: The objective of our study was to estimate the efficacy, side-effects, and compliance of a quadruple therapy containing esomeprazole in a group of dyspeptic elderly patients. PATIENTS AND METHODS: Consecutive elderly patients positive for H. pylori infection and not previously treated for eradication were enrolled. Therapy consisted of esomeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate tablets 240 mg, all twice-a-day with the midday and evening meals, for 10 days. Efficacy was evaluated using 13C-urea breath testing. Compliance was assessed after completing treatment and at follow up. Side effects were graded based on daily activities. RESULTS: Ninety-five dyspeptic patients (range 65-81 years), 52 men and 43 women, were enrolled. The intention-to-treat cure rate was 91% (81 of 89; 95% CI = 88-99%) and, 95% (81 of 85; 95% CI = 83-96%) per-protocol analysis. Compliance was excellent. Mild-moderate side effects occurred in 27 patients. CONCLUSIONS: Esomeprazole containing quadruple therapy was highly successful for initial eradication of H. pylori in elderly patients.     

Impact of Quadruple Regimen of Clarithromycin Added to Metronidazole-Containing Triple Therapy Against Helicobacter pylori Infection Following Clarithromycin-Containing Triple-Therapy Failure

Background: The establishment of an optimal second-line regimen for Helicobacter pylori infection is required. Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole, the effects of a quadruple regimen in second-line therapy are unknown. This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H. pylori infection.
Materials and Methods: Participants were 104 patients in whom first-line therapy containing proton pump inhibitor-amoxicillin-clarithromycin failed. Before starting second-line therapy, patients underwent endoscopy to obtain H. pylori strain for antibiotic susceptibility tests. Patients were randomized to receive rabeprazole (10 mg), amoxicillin (750 mg), and metronidazole (250 mg), either with clarithromycin (200 mg; RAMC group) or without (RAM group); all treatments were administered twice daily for 7 days. H. pylori eradication was confirmed by ¹³C-urea breath tests performed 2 to 3 months post-therapy.
Results: As shown by intention-to-treat/per-protocol analyses, the cure rates for H. pylori infection were 88.5%/93.9% and 82.7%/84.3% for the RAMC and RAM groups. Although the study probably had an insufficient power to show a significant difference between the cure rates of the two regimens, the eradication rates showed a clear trend in favor of the RAMC group. There were no severe side-effects in any group.
Conclusions: In Japan, the RAMC regimen is thought to be a promising alternative strategy for second-line eradication of H. pylori infection.     

Rabeprazole Can Overcome the Impact of CYP2C19 Polymorphism on Quadruple Therapy

Objectives: The prospective study was designed to clarify the impact of CYP2C19 on quadruple therapies and survey the efficacies of rabeprazole‐based quadruple therapy for Helicobacter pylori infection after failure of standard triple therapies. Patients and Methods: From January 2007 to March 2009, 1055 H. pylori‐infected patients received standard triple regimens (proton‐pump inhibitor (PPI), clarithromycin, and amoxicillin). Helicobacter pylori eradication was achieved in 865 (81.9%) subjects. One hundred ninety eradication‐failure patients were enrolled and randomly assigned to receive a 7‐day eradication therapy. Ninety‐six patients were treated with esomeprazole‐based quadruple rescue therapies (EB), while 94 patients were treated with rabeprazole‐based quadruple rescue therapies (RB). Follow‐up endoscopy was done 16 weeks later to assess the treatment response. Patients’ responses, CYP2C19 genotypes, and antibiotics resistances were also examined. Results: Intention‐to‐treat analysis revealed that RB had better eradication rates than EB (EB: 72.9%; 95% CI: 64.9–80.9% and RB: 78.7%; 95% CI 72.5–84.9%) (p value = .543). Per‐protocol results were EB = 75.3%; 95% CI: 70.3–80.3% and RB = 85.1%; 95% CI: 80.6–89.6% (p value = .0401). Both regimens had similar compliance (p value = 0.155) and adverse events (p value = 0.219). We also surveyed those patients without resistance of any antibiotics. RB still showed better outcome than EB. Our data showed that esomeprazole‐based regimen and CYP2C19 Hom EM genotype were important predictors for eradication failure. Conclusions: In quadruple therapy, rabeprazole‐based regimens had better efficacy than esomeprazole‐based regimens. CYP2C19 polymorphism also played an important role in quadruple therapy. It seems advisable to change PPI to rabeprazole in second‐line quadruple therapy.     

黄连素四联方案补救治疗幽门螺杆菌感染的有效性和安全性

目的:探索黄连素四联方案用于幽门螺杆菌感染根除失败患者补救治疗的有效性及安全性。方法:将经四联方案初次根除治疗失败并自愿接受补救治疗的130例患者按纳入顺序,以1:1的比例分配治疗,随机接受14天黄连素四联(埃索美拉唑20mg+胶体果胶铋200 mg+阿莫西林1000 mg,2/d+黄连素300 mg 3/d)或四环素四联(埃索美拉唑20 mg+胶体果胶铋200 mg+四环素750 mg+呋喃唑酮100 mg,2/d)方案的治疗。所有患者均于治疗14天及治疗结束至少28天后随诊,详细记录患者症状及不良反应情况。治疗结束至少28天后进行13C尿素呼气试验来判断幽门螺杆菌根除情况。结果:65例接受黄连素四联根除治疗,65例接受四环素四联方案治疗。两组分别有6例和4例患者因不良反应服药依从性小于80%,其余患者均完成了14天的治疗。黄连素组和四环素组的幽门螺杆菌根除率ITT分析分别为76.9%(50/65)和81.5%(53/65),P=0.520;PP分析分别为84.7%(50/59)和86.9%(53/61),P=0.739。黄连素组和四环素组不良事件总体发生率分别为49.2%和41.5%,P=0.370。结论:黄连素四联疗法用于幽门螺杆菌感染的二次根除治疗,根除率较高,未明显增加不良事件发生率,是有效及安全的补救治疗方案。     

Efficacy of metronidazole as second-line drug for the treatment of Helicobacter pylori Infection in the Japanese population: a multicenter study in the Tokyo Metropolitan Area

BACKGROUND: With the increase in the frequency of clarithromycin-resistant Helicobacter pylori (H. pylori), there is rising concern about the decline of the eradication rate of this infection following treatment. The Tokyo Hp Study Group examined the eradication rate in response to a second-line regimen consisting of proton pump inhibitor (PPI), amoxicillin, and metronidazole by conducting a multicenter study in the Tokyo Metropolitan Area. MATERIALS AND METHODS: Two hundred and twenty-eight patients with H. pylori infection, in whom the first-line therapy with a PPI, amoxicillin, and clarithromycin administered for 1 week had failed to eradicate the infection, were enrolled in this study. These cases were randomly assigned to one of the two second-line regimens containing metronidazole (PPI/AM500 or PPI/AM750) administered for 1 week. 13C-urea breath test was performed as a diagnostic method test for H. pylori infection not earlier than 8 weeks after the second-line therapy. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed an eradication rate of 87.6 and 90.6%, respectively, following PPI/AM500 treatment, and 86.9 and 88.6%, respectively, following PPI/AM750 treatment. Neither analysis revealed any significant difference in the eradication rate between PPI/AM500 and PPI/AM750 (p = .876 and .621, respectively). According to ITT and PP analyses, the eradication rates following treatment with PPI/AM500 were 85.2 and 88.5% with the use of lansoprazole, 62.5 and 62.5% with the use of omeprazole, and 93.2 and 96.5% with the use of rabeprazole, respectively. There was a significant difference in the eradication rates between PPI (omeprazole)/AM500 and PPI (rabeprazole)/AM500. In the case of PPI/AM750, the corresponding eradication rates were 84.8 and 87.0% with the use of lansoprazole, 92.9 and 92.9% with the use of omeprazole, and 92.9 and 92.9% with the use of rabeprazole, respectively. There were no significant differences in the eradication rates obtained with the use of the three PPIs. CONCLUSIONS: Both PPI/AM500 and PPI/AM750 administered for 1 week appeared to be highly effective second-line regimens for the treatment of H. pylori infection in Japanese patients. From the viewpoint of adverse events, PPI/AM500 appeared to be safe compared with PPI/AM750.