Seven-day quintuple regimen as a rescue therapy for Helicobacter pylori eradication

AIM: To determine the efficacy of two quintupleregimens for eradication of Helicobacter pylori(H. pylori) in patients who failed previous therapies.METHODS: This prospective, open-label, randomized controlled trial was a phase Ⅱ study conducted from April 2011 to March 2012 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 208 patients with dyspepsia who failed previous H. pylori eradication with a ten-day quadruple therapy were enrolled. A random block method was used to assign patients to one of two treatment groups. Patients in the first group were treated with 240 mg bismuth subcitrate, 20 mg omeprazole, 1000 mg amoxicillin, 500 mg clarithromycin and 500 mg tinidazole(BOACT group). Patients in the second group received a regimen containing 240 mg bismuth subcitrate, 20 mg omeprazole, 500 mg tetracycline, 500 mg metronidazole and 200 mg ofloxacin(BOTMO group). Both regimens were given twice daily for a duration of seven days. The eradication was confirmed by a 14 C urea breath test 12 wk after completion of therapy. Patient compliance and drug side effects were evaluated at the end of the treatment period. The success rates were calculated by intention-to-treat and per-protocol analyses.RESULTS: A total of 205 patients completed the course of treatment, with three patients excluded due to drug intolerance. The mean age of patients did not differ between the BOACT and BOTMO groups(41.6 ± 12.2 years vs 39.6 ± 11.8 years), and no significant differences were found between the two groups in terms of age, sex, smoking habits or the initial eradication regimen. The intention-to-treat and perprotocol eradication rates were significantly higher in the BOTMO group(86.5%, 95%CI: 0.85-0.87 and 86.7%, 95%CI: 0.80-0.89, respectively) compared with the BOACT group(75.5%, 95%CI: 0.73-0.76 and 76%, 95%CI: 0.69-0.80, respectively)(P 0.05). Univariate analyses for both groups did not show any association of sex, smoking and initial therapeutic regimen witheradiation rate(P 0.05 for all). Significantly more patients experienced side effects in the BOACT group compared to the BOTMO group(77.4% vs 36.6%, P 0.01). This difference was exemplified by increases in headache and taste disturbance(P 0.05).CONCLUSION: Quintuple therapy with a BOTMO regimen is an alternative second-line rescue therapy for Iranian patients with failed first-line eradication treatment of H. pylori.     

Helicobacter pylori therapy: Present and future

Helicobacter pylori(H.pylori) plays a crucial role in the pathogenesis of chronic active gastritis,peptic ulcer and gastric mucosa-associated lymphoid tissue-lymphoma,and is also involved in carcinogenesis of the stomach.H.pylori treatment still remains a challenge for physicians,since no current first-line therapy is able to cure the infection in all treated patients.Several factors may help in the eradication of therapy failure.We reviewed both bacterial and host factors involved in therapeutic management of the H.pylori infection.In addition,we evaluated data on the most successful therapy regimens-sequential and concomitant therapies-currently available for H.pylori eradication.     

序贯疗法和标准三联疗法根除幽门螺杆菌的疗效比较

目的:观察10d序贯疗法治疗幽门螺杆菌(Helicobacter pylori,H.pylori)的疗效及不良反应,与14d三联标准疗法比较H.pylori根除情况及经济学上有无优越性.方法:将103例经胃镜检查确诊为慢性胃炎或消化性溃疡且H.pylori阳性的患者随机分为两组,治疗组(10d序贯疗法)52例,前5d埃索美拉唑、阿莫西林,后5d埃索美拉唑、克拉霉素、替硝唑.对照组(14d标准三联疗法)51例,埃索美拉唑、阿莫西林、克拉霉素14d.所有患者停药4wk后复查13C呼气试验或胃镜检查,判断H.pylori根除情况.结果:治疗组H.pylori根除率为90.4%,与对照组(90.2%)比较无统计学差异(P=1.000);两组不良反应发生率分别为12/52(23.1%)、18/51(35.3%),两组比较无统计学差异(P=0.172);治疗组费用为380.6元,较对照组(677.88元)明显减低.结论:10d序贯疗法的H.pylori根除率不低于标准14d三联疗法,2组不良反应发生率相似,但10d序贯疗法根除H.pylori的效价比更高.     

Helicobacter pylori Treatment Strategies in Singapore

The management of Helicobacter pylori infection in Singapore remains a clinical challenge. Similar to other regions, there has been an increase in antibiotic resistance rates through the years. Nonetheless, over the past two decades, clarithromycin-based triple therapy has continued to be used as the first line treatment option, with an eradication rate exceeding 90%, although the accepted treatment duration must now be lengthened from 1 to 2 weeks to maintain efficacy. Concomitant and sequential therapies did not demonstrate superiority over standard triple therapy. Current empiric second line treatment utilizes either bismuth-based quadruple therapy or levofloxacin-based triple therapy, but outcomes remain less than ideal. Identifying options to further improve treatment success rates is challenging. Strategies being considered include the use of potent acid suppressants, such as vonoprazan, and H. pylori culture and antibiotic susceptibility testing-guided therapy.     

Tailored eradication strategy vs concomitant therapy for Helicobacter pylori eradication treatment in Korean patients

BACKGROUNDAntibiotic resistance to Helicobacter pylori (H. pylori) infection, which ultimately results in eradication failure, has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has received attention. AIMTo investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, concomitant therapy (CT) regimen. METHODSWe included patients (> 18 years) with an H. pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020. After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were assessed and compared between the two groups. H. pylori infection was diagnosed using a rapid urease test, Giemsa stain, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR). Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation. For the TT group, a DPO-PCR test, which detected A2142G and/or A2143G point mutations, and a clarithromycin resistance test were performed. Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen. RESULTSOf the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001).CONCLUSIONThe DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates.     

8d与10d序贯疗法根除幽门螺杆菌的疗效比较

目的:比较雷贝拉唑、阿莫西林、克拉霉素、奥硝唑组成的8d与10d序贯疗法根除幽门螺杆菌(H.pylori)的疗效.方法:将经胃镜检查确诊为慢性胃炎和消化性溃疡,且H.pylori阳性的217例患者随机分为2组,8d组(n=104)方案:前4d,雷贝拉唑+阿莫西林;后4d,雷贝拉唑+克拉霉素+奥硝唑.10d组(n=113)方案:前5d,雷贝拉唑+阿莫西林;后5d,雷贝拉唑+克拉霉素+奥硝唑.根除治疗后复查14C-尿素呼气试验,比较两组H.pylori根除率.结果:8d组和10d组H.pyloriITT根除率分别为89.3%和91.2%,PP根除率分别为92.0%和93.7%.两种分析方法比较两组的根除率差异均无统计学意义(P>0.05),但8d序贯疗法降低了成本-效果比,减轻了患者的经济负担.两种方案症状缓解率及不良反应发生率的差异无统计学意义(P>0.05).结论:8d序贯疗法可以获得较高的H.pylori根除率和症状缓解率,且经济、安全,是一种可供选择的一线治疗方案.     

幽门螺杆菌感染治疗现状与展望

随着时间的变迁,幽门螺杆菌(Helicobacter pylori,H.pylori)对常用抗生素的耐药率逐渐增加,其根除率逐渐下降。四联疗法已成为当前治疗H.pylori的主要一线方案,另外欧州MaastrichtIV共识意见中还推荐了序贯疗法和伴同疗法。在H.pylori对常用抗生素耐药的情况下,对于如何提高H.pylori根除率,我国H.pylori学者正在进行H.pylori治疗新路径探索:(1)三联(或四联)联合中药治疗;(2)三联(或四联)联合益生菌治疗;(3)探索口腔H.pylori对H.pylori根除治疗的影响;(4)强调个体化治疗。今天的新思路也许会成为明天治疗H.pylori的新手段。     

Adjuvant probiotics improve the eradication effect of triple therapy for Helicobacter pylori infection

AIM:To investigate whether the addition of probiotics can improve the eradication effect of triple therapy for Helicobacter pylori (H. pylori ) infection. METHODS:This open randomized trial recruited 234 H. pylori positive gastritis patients from seven local centers. The patients were randomized to one-week standard triple therapy (omeprazole 20 mg bid , clarithromycin 500 mg bid , and amoxicillin 1000 mg bid ; OCA group, n = 79); two weeks of pre-treatment with probiotics, containing 3 × 107 Lactobacillus acidophilus per day, prior to one week of triple therapy (POCA group, n = 78); or one week of triple therapy followed by two weeks of the same probiotics (OCAP group, n = 77). Successful eradication was defined as a negative C13 or C14 urease breath test four weeks after triple therapy. Patients were asked to report associated symptoms at baseline and during follow-up, and side effects related to therapy were recorded. Data were analyzed by both intention-to-treat (ITT) and per-protocol (PP) methods. RESULTS:PP analysis involved 228 patients, 78 in the OCA, 76 in the POCA and 74 in the OCAP group. Successful eradication was observed in 171 patients; by PP analysis, the eradication rates were significantly higher (P = 0.007 each) in the POCA (62/76; 81.6%, 95% CI 72.8%-90.4%) and OCAP (61/74; 82.4%, 95% CI 73.6%-91.2%) groups than in the OCA group (48/78; 61.5%, 95% CI 50.6%-72.4%). ITT analysis also showed that eradication rates were significantly higher in the POCA (62/78; 79.5%, 95% CI 70.4%-88.6%) and OCAP (61/77; 79.2%, 95% CI 70%-88.4%) groups than in the OCA group (48/79; 60.8%, 95% CI 49.9%-71.7%), (P = 0.014 and P = 0.015). The symptom relieving rates in the POCA, OCAP and OCA groups were 85.5%, 89.2% and 87.2%, respectively. Only one of the 228 patients experienced an adverse reaction. CONCLUSION:Administration of probiotics before or after standard triple therapy may improve H. pylori eradication rates.     

Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.     

幽门螺杆菌根除前后血清抗体滴度变化的临床意义

目的探讨幽门螺杆菌（Hp）血清抗体细胞毒素相关蛋白A（CagA）、尿素酶（Ure）滴度的变化在Hp根除疗效中的临床意义。方法采用经胃镜及快速尿素酶试验确诊为Hp相关性消化性溃疡患者118例,以蛋白芯片方法检测血清CagA、Ure抗体,观察其根除前、根除后8周、24周抗体滴度变化。结果118例患者有102例Hp根除,根除率为86.4%。根除治疗成功组在治疗后8周CagA、Ure抗体滴度下降无显著性,24周后则显著下降（P〈0.05）,下降幅度分别为63.5%、41.3%,CagA及Ure抗体的下降幅度比较差异有统计学意义（P〈0.05）。而根除治疗失败组的CagA、Ure抗体滴度无明显变化（P〉0.05）。结论蛋白芯片法动态观察血清CagA、Ure抗体水平8～24周以上,可作为评估根除Hp疗效的一种参考方法,且CagA抗体可能更有意义。     

幽门螺杆菌根除效果的影响因素分析

幽门螺杆菌(Helicobacter pylori,H.pylori)感染是最常见的细菌感染之一,影响着世界约50%的人口,被世界卫生组织定义为胃癌致病因子。H.pylori根除治疗可以降低消化性溃疡、胃癌等疾病的发病风险。目前H.pylori根除率呈逐渐下降的趋势。加深对其根除率影响因素的了解,可能有助于制定更为有效的根除治疗或预防感染的方案。本文结合国内外相关研究,对影响H.pylori根除率的因素作一概述。     

Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication: A randomized study in Japan

AIM:To find the way to improve the eradication rate of first-line therapy in Japanese patients.METHODS:We prospectively compared the effectiveness of 7-d quadruple therapy to standard 7 d triple therapy in Japanese patients infected with Helicobacter pylori(H.pylori).One hundred and nineteen patients were randomly assigned to receive 7-d non-bismuth quadruple therapy with lansoprazole,amoxicillin,clarithromycin and metronidazole(LACM7) or 7-d triple therapy with lansoprazole,amoxicillin and clarithromycin(LAC7).After three months,H.pylori status was analyzed by 13C-urea breath test.Incidence rates of adverse events were evaluated by use of questionnaires.RESULTS:By intention-to-treat(ITT) analysis,the eradication rate in the LACM7 group was 94.9%,which was significantly higher than the LAC7 group(68.3%,P < 0.001).Per protocol analysis also showed a significantly higher eradication rate in the LACM7 group(98.3%) than the LAC7 group(73.2%,P < 0.001).Nevertheless,the incidence of serious adverse events did not differ between the two groups(RR:1.10,95% CI:0.70-1.73,P = 0.67).CONCLUSION:Seven day non-bismuth quadruple therapy(LACM7) was superior to standard 7-d triple therapy(LAC7) for first-line eradication.     

兰索拉唑三联疗法根除幽门螺杆菌的疗效及耐药研究

目的 研究以兰索拉唑为基础的不同治疗方案对幽门螺杆菌(H.pylori)根除率的影响并了解湖南地区H.pylori 耐药情况.方法 将76例H.pylori感染患者分成兰索拉唑加克拉霉素、阿莫西林组(LCA组)38例和兰索拉唑加克拉霉素与甲硝唑组(LCM组)38例,治疗1周,治疗前采用快速尿素酶试验(RUT)、14C-尿素呼气试验(14C-UBT)、组织学检查筛选,入选患者进行H.pylori培养及药物敏感性检测.治疗后停用抗生素至少4周行14C-UBT复查.结果 LCA组共有31例完成治疗,26例H.pylori 被根除, 根除率为83.87%;LCM组共有35例完成治疗,21例H.pylori 被根除, 根除率为60.00%.LCA组根除率明显高于LCM组(P＜0.05).阿莫西林、克拉霉素及甲硝唑耐药率分别为0.00%、28.00%和92.00%,对克拉霉素及甲硝唑均耐药率为24.00%;两组药物副作用发生率比较无明显差别(P＞0.05).结论 (1) 兰索拉唑联合克拉霉素、阿莫西林组较联合克拉霉素与甲硝唑组H.pylori根除率高;(2)湖南地区H.pylori对甲硝唑耐药率最高(92.00%),克拉霉素次之(28.00%).尚未发现对阿莫西林耐药的菌株.     

Third-line rescue therapy for Helicobacter pylori infection

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.     

噬菌体治疗耐药性幽门螺杆菌的研究进展

幽门螺杆菌感染是胃癌重要致病因子。目前,幽门螺杆菌对抗生素耐药情况日趋普遍。噬菌体治疗作为一种生物疗法存治疗幽门螺杆菌方面有极大的潜力。本文就噬菌体治疗耐药性幽门螺杆菌的现状及趋势进行综述。     

Successful isolation of Helicobacter pylori after prolonged incubation from a patient with failed eradication therapy

Helicobacter pylori （H pylori）, a gastric pathogen, is a major cause of chronic gastritis and peptic ulcer disease, and is an important risk factor for the development of gastric malignancies. Culture of the bacterium from gastric biopsy is essential for the determination of drug resistance of Hpylori. However, the isolation rates of H pylorifrom infected individuals vary from 23.5% to 97% due to a number of factors such as biopsy preparation, cultural environment, medium and the method adopted. In the present case, we found that a prolonged incubation period of up to 19 d allowed successful isolation of H pylori from a patient who received triple therapy that failed to eradicate the bacterium.