Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice

BACKGROUND: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined. AIMS: To evaluate proton pump inhibitor-based triple therapies as first-line eradication regimens in clinical practice, and to establish the efficacy of second-line regimens in the context of an initial failed eradication attempt. METHODS: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first-line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2-week proton pump inhibitor-based triple therapy regimen as described, and 12 patients received a further 1-week proton pump inhibitor-based triple therapy regimen. RESULTS: Including 308 patients, the intention-to-treat (ITT) eradication rates for OAC and OMC as first-line regimens were 72% (95% CI: 63-80%) and 73% (95% CI: 67-79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow-up gives an initial eradication rate of 78% (95% CI: 69-86%) for OAC and 79% (95% CI: 73-85%) for OMC. There were 60 patients (21%; 95% CI: 17-26%) in whom the initial eradication attempt was unsuccessful. With second-line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58-73%) patients. The eradication rates with the quadruple regimen and 2-week triple therapy regimens were 75% (95% CI: 56-94%) and 80% (95% CI: 63-98%) respectively (P = 0. 71). The eradication rate with a repeat 1-week regimen was 33% (95% CI: 7-60%). CONCLUSIONS: The eradication rates achieved in this 'in practice' study with recommended first-line 1-week proton pump inhibitor-based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1-week proton pump inhibitor-based triple therapy regimen was not successful as a salvage therapy. Both the 2-week proton pump inhibitor-based triple therapy regimen and the 1-week quadruple therapy regimen were successful second-line treatments in >/=75% of patients.     

Meta-analysis: high-dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication

Background The evidence on whether high‐dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed. Aim To evaluate the evidence on the usefulness of high‐dose PPI in standard triple therapy by performing a systematic review and a meta‐analysis. Methods A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high‐dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager. Results Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention‐to‐treat cure rate of 82% was achieved with high‐dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01–1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg. Conclusion High‐dose PPI seems more effective than standard‐dose for curing H. pylori infection in 7‐day triple therapy.     

Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection

BACKGROUND: There have been no reports that describe whether 5-day quadruple therapy (rabeprazole + amoxicillin + clarithromycin + metronidazole; RACM) could substitute for standard 7-day triple therapy as a first-line therapy for Helicobacter pylori. PATIENTS AND METHODS: This study was designed as a randomized prospective single centre study. A total of 160 H. pylori-positive patients who had not received therapy were given either a 5-day RACM regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d.) or a 7-day RAC regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d. and clarithromycin 200 mg b.d.). Cure of the infection was assessed by a (13)C urea breath test 1 month after the completion of therapy. RESULTS: The eradication rates of the 5-day RACM regimen and the 7-day RAC regimen were 93% (95% CI: 84--97%) and 81% (95% CI: 71--89%) by intention-to-treat analysis, 94% (95% CI: 86--98%) and 83% (95% CI: 73--91%) by all-patients-treated analysis analysis and 95% (95% CI: 87--98%; P < 0.05) and 82% (95% CI: 72--90%) by per protocol analysis, respectively. No serious adverse effect was observed, and 99% of the patients reported complete compliance. CONCLUSIONS: The cure rate of the 5-day RACM regimen was more effective than the 7-day RAC regimen, suggesting that this regimen could be preferable as a first-line therapy for H. pylori infection.     

Helicobacter pylori eradication with proton pump inhibitor-based triple therapies and re-treatment with ranitidine bismuth citrate-based triple therapy

BACKGROUND: It has been suggested that short-term triple therapy comprising a proton pump inhibitor, plus clarithromycin and amoxycillin be used as first choice in treating H. pylori infection, while eradication failure patients should be further treated with a quadruple therapy. Nevertheless, conflicting results have been reported using these treatment regimens in different countries. METHODS: A total of 278 patients with H. pylori infection were randomised to receive one-week triple therapy, comprising clarithromycin 500 mg b.d., amoxycillin 1 g b.d., and either omeprazole 20 mg b.d. (OAC; 90 patients), or pantoprazole 40 mg b.d. (PAC; 95 patients), or lansoprazole 30 mg b.d. (LAC; 93 patients). H. pylori infection at entry, and eradication 4-6 weeks after therapy had ended, were assessed by rapid urease test and histology on biopsies from the antrum and the corpus. When eradication did not occur, patients were given a 2-week treatment comprising ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s. and tinidazole 500 mg b.d. (RBTT). Eradication in these patients was assessed 4-6 weeks after conclusion of treatment by a further endoscopy. RESULTS: Six patients were lost to the follow-up. At the end of the first course of treatment, the overall H. pylori eradication rate was 78% (95% CI: 73-83) and 79% (95% CI: 75-84) at 'intention-to-treat' (ITT) and 'per protocol' (PP) analysis, respectively, without any statistically significant difference between treatment regimens, although a trend for better results with the omeprazole combination was observed. Moreover, H. pylori eradication was achieved in 82% (95% CI: 75-97) (ITT) and 86% (95% CI: 69-94) (PP) of 38 patients re-treated with RBTT regimen. CONCLUSIONS: Our data found that this short-term triple therapy is not a satisfactory treatment (< 80% eradication rate) for H. pylori infection. The 2-week triple therapy used as re-treatment in eradication failure patients yielded more promising results.     

Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis

BACKGROUND: Triple therapies combining a double dose of proton pump inhibitor plus two antibiotics are the standard treatment for Helicobacter pylori infection. Some reports suggest that the use of half the dose of proton pump inhibitor is equally effective. AIM: To compare the efficacy of a single vs. double dose of proton pump inhibitor in triple therapy. METHODS: We conducted a MEDLINE search. The search strategy included the words (pylori) AND (triple, PPI, proton pump, omeprazole, rabeprazole, pantoprazole, lansoprazole, clarithromycin, amoxicillin, amoxycillin or metronidazole). Abstracts of the articles obtained and papers presented at the European Helicobacter pylori Study Group and American Gastroenterological Association congresses from 1996 to 2001 were examined. Inclusion criteria were: (i) randomized studies with at least two branches of triple therapy including a proton pump inhibitor and two standard antibiotics; (ii) branches could differ only in terms of proton pump inhibitor dosage. A meta-analysis was conducted using conventional shareware (Review Manager 4.1). RESULTS: Thirteen studies met the inclusion criteria with a total of 2391 patients. Cure rates with double doses of proton pump inhibitor were higher in both the intention-to-treat analysis (83.9% vs. 77.7%; Peto odds ratio, 1.51; 95% confidence interval, 1.23-1.85; P < 0.01) and per protocol analysis (89% vs. 81%; Peto odds ratio, 1.96; 95% confidence interval, 1.55-2.47; P < 0.01). CONCLUSION: Triple therapies containing a single dose of proton pump inhibitor are less effective than those containing a standard double dose of proton pump inhibitor.     

Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection

BACKGROUND: Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM: To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD: Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS: One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS: The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.     

10天序贯疗法与标准三联方案治疗幽门螺杆菌感染的疗效对比

目的：比较10d序贯疗法与标准三联方案治疗幽门螺杆菌（ HP）感染的疗效。方法选取2010年6月—2013年7月某院收治的经胃镜检查及组织学检查确诊为慢性胃炎或消化性溃疡且13 C-尿素呼气实验阳性患者87例,随机分为治疗组（41例）与对照组（46例）。治疗组予以10d序贯疗法,对照组予以标准三联方案。观察两组患者HP根除率、溃疡愈合率、不良反应发生情况及临床疗效。结果治疗组患者HP根除率及溃疡愈合率高于对照组,差异有统计学意义（P<0.05）;两组患者不良反应发生率比较,差异无统计学意义（P>0.05）;治疗组患者总有效率高于对照组（ P<0.05）。结论10d序贯疗法治疗HP感染的疗效显著,HP根除率高,不良反应小。     

序贯疗法与标准三联疗法治疗幽门螺杆菌的临床疗效比较

目的：研究序贯疗法与标准三联疗法治疗幽门螺杆菌的临床疗效。方法选取幽门螺杆菌阳性患者120例,按照数字表法将患者分为A组和B组,每组60例。 A组给予序贯疗法（奥美拉唑＋阿莫西林治疗5 d以后继续以奥美拉唑＋克拉霉素＋替硝唑治疗5 d）治疗,B组给予标准三联疗法（奥美拉唑＋阿莫西林＋克拉霉素）治疗,比较两组幽门螺杆菌根除率、溃疡愈合总有效率以及不良反应。结果 A组幽门螺杆菌的根除率91．7％（55／60）,显著高于对照组的71．7％（43／60）（χ^2＝11．915,P＝0．023）;A组溃疡愈合总有效率96．7％（58／60）,显著高于B组的88．3％（53／60）（χ^2＝9．915,P＝0．038）;两组不良反应发生率差异无统计学意义（χ^2＝4．735,P＝0．072）。结论序贯疗法相比标准三联疗法治疗幽门螺杆菌具有较好的效果,能显著提高幽门螺杆菌的根除率,且无严重不良反应。     

艾普拉唑7d三联疗法及10d序贯疗法根除幽门螺杆菌的临床疗效

目的观察艾普拉唑7 d三联疗法及10 d序贯疗法根除幽门螺杆菌（Hp）的临床疗效。方法 142例经电子胃镜、RUT检查证实Hp阳性的慢性胃炎患者,随机分成3组。A组予艾普拉唑5 mg+阿莫西林克拉维酸钾0.914 g+呋喃唑酮0.1g,bid,疗程7 d;B组予艾普拉唑5 mg+阿莫西林克拉维酸钾0.914 g,疗程5 d,继之艾普拉唑5 mg+克拉霉素0.5 g+呋喃唑酮0.1g,疗程5 d,共计10 d,每天均给药2次;C组予埃索美拉唑20 mg+阿莫西林克拉维酸钾0.914 g+呋喃唑酮0.1 g,bid,疗程7 d。疗程结束4周后行¹⁴C-尿素呼气试验(¹⁴C-UBT),观察Hp根除率、症状缓解率及不良反应发生情况。结果 A、B、C组患者症状缓解率比较差异无统计学意义（P>0.05）;Hp根除率分别为60%、58.54%和55.26%,经检验P均>0.05。3组患者均无明显不良反应发生。结论 3组用药方案虽能达到良好的症状缓解率,但Hp根除率均未超过60%,低于理想标准。     

Review article: Helicobacter pylori "rescue" regimen when proton pump inhibitor-based triple therapies fail

Even with the currently most effective treatment regimens, about 10-20% of patients will fail to obtain eradication of Helicobacter pylori infection. Therefore, in designing a treatment strategy, we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of second-line treatment depends on which treatment was used initially, as re-treatment with the same regimen is not recommended. Therefore, it is not necessary to perform culture after the first eradication failure. Assessment of the sensitivity of H. pylori to antibiotics only after failure of the second treatment is suggested in clinical practice. Different possibilities of empirical treatment have been suggested. After failure of proton pump inhibitor-amoxicillin-clarithromycin, quadruple therapy has generally been used. More recently, replacement of the proton pump inhibitor and the bismuth compound by ranitidine bismuth citrate has also achieved good results. After proton pump inhibitor-amoxicillin-nitroimidazole failure, re-treatment with proton pump inhibitor-amoxicillin-clarithromycin has been proven to be effective. Finally, first-line treatment should not combine clarithromycin and metronidazole in the same regimen, because of the problem of resistance to both antibiotics. Recently, rifabutin-based rescue therapies have been shown to constitute an encouraging strategy for eradication failures, as they are effective against H. pylori strains resistant to antibiotics.     

Pantoprazole-based 10-day triple therapy is effective in Helicobacter pylori eradication

Aim:

To investigate the efficacy of a short course of pantoprazole-based triple therapy in Helicobater pylori eradication in a single-centre pilot study.

Methods:

Patients with active or healed duodenal ulcer or with gastric erosions or gastritis, all of whom were H. pylori-positive, received 10 days of twice-daily open treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and tinidazole 500 mg. H. pylori was assessed at entry and 28–35 days after the end of treatment by rapid urease test (at entry only), culture and antimicrobial sensitivity, histology and ¹³ C urea breath test. The criterion for eradication was a negative result in all three tests.

Results:

Seventy patients were treated, of whom four were excluded from analysis due to major deviations from the study protocol. Eradication of H. pylori was achieved in 57/66 patients (per protocol analysis 86% (95% CI: 78–95%)) and was higher in patients with organisms sensitive to nitroimidazole before treatment (sensitive: 47/53 (89%), insensitive: 10/13 (77%)). There was marked reduction in acute gastritis throughout the stomach while chronic gastritis decreased only in the corpus. Healing was achieved in all 24 patients with active duodenal ulcer. Treatment was complied with; only one patient missed one of the 20 doses. Adverse events were of mild or moderate intensity and did not require withdrawal from treatment.

Conclusion:

A short course of pantoprazole-based triple therapy is well tolerated and effective in eradicating H. pylori.

     

One-week triple vs. quadruple therapy for Helicobacter pylori infection - a randomized trial

BACKGROUND: Seven-day triple therapy including omeprazole, clarithromycin and amoxicillin has become the treatment of choice for Helicobacter pylori infection. However, 7 days of classical quadruple therapy combining omeprazole, tetracycline, metronidazole and bismuth may be an alternative to triple therapy. AIM: To compare triple vs. quadruple therapy for H.pylori eradication. METHODS: Three hundred and thirty-nine patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomized to receive omeprazole, 20 mg, amoxicillin, 1 g, and clarithromycin, 500 mg, all b.d., or omeprazole, 20 mg b.d., tetracycline chloride, 500 mg, metronidazole, 500 mg, and bismuth subcitrate, 120 mg, all t.d.s. Cure was defined as a negative urea breath test at least 2 months after treatment. RESULTS: Per protocol and intention-to-treat cure rates were 86%[95% confidence interval (CI), 80-91%] and 77% (95% CI, 70-83%) for triple therapy, and 89% (95% CI, 82-93%) and 83% (95% CI, 76-88%) for quadruple therapy. No significant differences between the groups were found in the cure rates, compliance or side-effects. CONCLUSION: One-week triple and quadruple therapy show similar results when used as first-line eradication treatment.     

Levofloxacin-based triple therapy vs. quadruple therapy in second-line Helicobacter pylori treatment: a randomized trial

BACKGROUND: Levofloxacin has been shown to be effective in Helicobacter pylori eradication. Two 10-day levofloxacin-based triple therapies were compared with standard 7- and 14-day quadruple regimens in second-line treatment. METHODS: Two hundred and eighty consecutive patients who failed to respond to standard triple therapy (clarithromycin, amoxicillin, rabeprazole) were randomly assigned to four groups: (1) levofloxacin 500 mg o.d., amoxicillin 1 g b.d., rabeprazole 20 mg b.d. for 10 days (LAR, n = 70); (2) levofloxacin 500 mg o.d., tinidazole 500 mg b.d., rabeprazole 20 mg b.d. for 10 days (LTR, n = 70); (3) tetracycline 500 mg q.d.s., metronidazole 500 mg t.d.s., bismuth salt 120 mg q.d.s., rabeprazole 20 mg b.d. for 7 days (7TMBR, n = 70); and (4) for 14 days (14TMBR, n = 70). Helicobacter pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: The eradication rate was 94% in the LAR group and 90% in the LTR group in both intention-to-treat and per protocol analyses. Helicobacter pylori eradication was achieved in 63 and 69% of the 7TMBR group and in 69 and 80% of the 14TMBR group in intention-to-treat and per protocol analysis, respectively. Side-effects were significantly lower in the LAR and LTR groups than in the 14TMBR group. CONCLUSION: Ten-day levofloxacin-based therapies are better than standard quadruple regimens as second-line option for H. pylori eradication.     

两种序贯疗法与十天三联疗法根除幽门螺杆菌感染疗效比较

目的评价含呋喃唑酮和含替硝唑的两种序贯疗法和十天三联疗法根除幽门螺杆菌(H.pylori)的疗效。方法将163例消化性溃疡和慢性胃炎且Hp阳性的患者随机分为3组。序贯疗法A组54例,前5d予埃索美拉唑20mg+阿莫西林1.0g,2次/d;后5d予埃索美拉唑20mg+克拉霉素500mg+呋喃唑酮100mg,2次/d。序贯疗法B组55例,前5d予埃索美拉唑20mg+阿莫西林1.0g,2次/d;后5d予埃索美拉唑20mg+克拉霉素500mg+替硝唑500mg,2次/d。三联疗法C组54例,予埃索美拉唑20mg+阿莫西林1.0g+克拉霉素500mg,2次/d,疗程10d。记录治疗期间发生的不良反应。疗程结束停药至少4周以上复查14C-UBT(尿素呼气试验),判断H.pylori根除情况。结果按试验方案(PP)分析和意向处理(ITT)分析,A组根除率分别为92.0%、85.2%;B组分别为77.6%、69.1%;C组分别为73.5%、66.7%。A组与B、C组分别相比较,差异均有统计学意义(均P<0.05);B组与C组比较,差异无统计学意义(P>0.05)。结论含呋喃唑酮的序贯疗法疗效明显高于含替硝唑序贯疗法及十天三联疗法,可以考虑作为H.pylori感染患者初治的一线治疗方案。     

5-day vs. 7-day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication

AIM: To determine whether a 5-day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7-day regimen. METHODS: A total of 139 H. pylori-infected patients were randomized to receive either a 5-day or 7-day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C-urea breath test. RESULTS: On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance. CONCLUSIONS: Our 5-day regimen of RCA yielded inferior results, whereas the 7-day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor-clarithromycin-amoxicillin therapies cannot be recommended.