Only four days of quadruple therapy can effectively cure Helicobacter pylori infection

Aim: To determine whether 4 days of quadruple therapy using bismuth, tetracycline and metronidazole combined with omeprazole is effective treatment for Helicobacter pylori infection. Methods. Non-ulcer dyspepsia, as well as chronic peptic ulcer patients with biopsy-proven H. pylori infection received 4 days of quadruple therapy. They were pre-treated with 3 days of omeprazole. At least 5–6 weeks later, endoscopy was repeated with 10 biopsies for urease test, histology and culture to establish cure of infection. Results: None of the 54 patients included was lost to follow-up but two had a ¹⁴C-urea breath test instead of endoscopy. Side-effects did not interfere with compliance. Forty-nine out of 54 patients (91 %; 95% Cl: 80–97 %) were cured. Metronidazole susceptibility data were available from 43 pre-treatment isolates. Of these 38/40 (95 %) with a metronidazole-sensitive strain, and one of three with a metronidazole-resistant strain were cured. Conclusions: Four days of quadruple therapy after omeprazole pre-treatment is a feasible, well tolerated, and effective treatment for N. pylori infection, especially in those carrying a metronidazole-sensitive strain. It seems that in quadruple therapy, cure rate and treatment duration have a non-linear relation. Our results need confirmation, but for patients suffering from side-effects with the 7-day regimen stopping treatment after 4 days is justified.     

Long-term follow-up after cure of Helicobacter pylori infection with 4 days of quadruple therapy

Background : We have shown that 4 days of quadruple therapy after omeprazole pre-treatment is an effective therapy for curing H. pylori infection. In this study we investigated whether this regimen would maintain the high cure rate during long-term follow-up. Some recent studies have reported high recurrence rates after apparent cure. Apparently not all methods to test for cure have sufficient sensitivity to pick up small numbers of residual bacteria. This study also served to investigate whether our methods to test for cure 5–6 weeks post-treatment were reliable.
Methods : All patients from a previous study were invited to return for a ¹⁴C-urea breath test and serology. A representative group of 37 patients (76%) returned for a urea breath test and serology. The mean follow-up was 14.7 months (range 11.4–23.6 months).
Results : None of the 37 patients had a positive urea breath test result. IgG antibody titres fell steadily in all patients, showing a mean decrease of 83% at the end of the follow-up. None of the patients showed an increase in titre. Reinfection was therefore 0% (0 of 37).
Conclusion : Four days of quadruple therapy seems to be an effective therapy for the eradication of H. pylori as evidenced after long-term follow-up. Our biopsy methodology is reliable in identifying treatment failures 5–6 weeks post-treatment.     

四联疗法治疗幽门螺杆菌感染的疗效分析

目的：探讨四联疗法治疗幽门螺杆菌（Hp）感染的临床疗效。方法：将184例幽门螺杆菌感染患者,随机分为四联疗法组和标准三联疗法组。四联疗法组采用呋喃唑酮+阿莫西林+埃索美拉唑+枸橼酸铋钾胶囊,治疗周期10d;标准三联疗法组采用埃索美拉唑+克拉霉素+阿莫西林,治疗周期14d。结果：四联疗法组治疗幽门螺杆菌感染总有效率为89.69%,按PP分析,根除幽门螺杆菌率为88.66%,按ITT分析,为86.87%;标准三联疗法组总有效率为78.57%,按PP分析,根除幽门螺杆菌率为77.38%,按ITT分析,为76.47%。两组有效率和复发率比较差异显著（P＜0.05）。结论：四联疗法治疗幽门螺杆菌（Hp）感染有较高的治愈率。     

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.     

Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta-analysis

BACKGROUND: Triple therapy (proton pump inhibitor, clarithromycin and amoxicillin or an imidazole) is the first-line treatment for Helicobacter pylori infection. However, the effectiveness of triple therapy is decreasing due to the increase in antibiotic resistance. Quadruple therapy (proton pump inhibitor, tetracycline, metronidazole and a bismuth salt) is a very effective regimen even in areas of high prevalence of antibiotic resistance, and may be an alternative first-line treatment. AIM: To compare triple vs. quadruple therapy for the first-line treatment of H. pylori infection. METHODS: An extensive literature search was performed to identify randomized trials comparing triple vs. quadruple therapy. Selected trials were included in a meta-analysis using Review Manager 4.1. RESULTS: Four studies met the inclusion criteria. Eradication rates with quadruple therapy were slightly higher in both the intention-to-treat (81% vs. 78%; odds ratio, 0.83; 95% confidence interval, 0.61-1.14) and per protocol (88% vs. 85%; odds ratio, 0.81; 95% confidence interval, 0.55-1.20) analysis, although the differences were not statistically significant. Nor were there significant differences in compliance or adverse effects between the therapies. CONCLUSION: Triple and quadruple therapies seem to be roughly equivalent in terms of effectiveness, compliance and side-effects profile when administered as first-line treatment for H. pylori infection.     

One-day intensified lansoprazole-quadruple therapy for cure of Helicobacter pylori infection

Background : Peptic ulcer patients need to be treated with antimicrobials to cure Helicobacter pylori infection. Seven-day quadruple therapy is the regimen with the highest cure rates. An ultra-short quadruple therapy was evaluated prospectively.
Methods : Forty-six consecutive H. pylori positive patients (33 had proven ulcer disease) were prescribed lansoprazole 30 mg b.d. on days 1–4, and on day 4 they received in addition tripotassium dicitrato bismuthate 120 mg, tetracycline 250 mg and metronidazole 250 mg at 09.00, 11.00, 13.00, 15.00, 17.00, 19.00, 21.00, 23.00 hours. Repeat endoscopy with biopsies for CLOtest, Giemsa stain and culture was carried out 6 weeks later.
Results : Follow-up was complete. Overall cure rate (all three biopsy-based tests negative) was 26/46 (57%; 95% CI: 41–71%). Antibiotic sensitivity was available in 42. Thirty-nine carried a metronidazole sensitive strain and 23/39 (59%) were cured, three carried a resistant strain and therapy failed in all. Three out of four in whom susceptibility was unknown were cured. Metronidazole resistance was induced in 8 out of 16 with a sensitive strain. Only one patient (3%) reported severe side effects.
Conclusions : This convenient quadruple regimen showed that a short contact time is sufficient to kill H. pylori in vivo . Since 57% of patients are cured with a 14-h treatment, a slightly longer treatment duration may increase the cure rate to above 90%.     

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection

Background

We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection.

Methods

From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days; or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary.

Results

Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects.

Conclusions

With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

     

Nitrofurantoin quadruple therapy for Helicobacter pylori infection: effect of metronidazole resistance

BACKGROUND: Antibiotic resistance has increasingly been recognized as the major cause of treatment failure for Helicobacter pylori infection. New therapies for patients with metronidazole- or clarithromycin-resistant H. pylori are needed. AIM: To investigate the role of nitrofurantoin quadruple therapy for the treatment of H. pylori. METHODS: Patients with confirmed H. pylori infection received nitrofurantoin (100 mg t.d.s.), omeprazole (20 mg b.d.), Pepto-Bismol (two tablets t.d.s.), and tetracycline (500 mg t.d.s.) for 14 days. Four or more weeks after the end of therapy, outcome was assessed by repeat endoscopy with histology and culture or urea breath testing. RESULTS: Thirty patients were entered, including 25 men and five women; the mean age was 54.9 years. The most common diagnoses were duodenal ulcer (23%) and GERD (18%). The intention-to-treat cure rate was 70% (95% CI: 50.6-85%). Nitrofurantoin quadruple therapy was more effective with metronidazole-sensitive strains (88%; 15 out of 17) than with metronidazole-resistant strains (33%; three out of nine; P=0.008). Two of the treatment failures had pre-treatment isolates susceptible to metronidazole, which were resistant after therapy. CONCLUSIONS: Because nitrofurantoin quadruple therapy performed inadequately in the presence of metronidazole resistance, we conclude that nitrofurantoin is unlikely to find clinical utility for the eradication of 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.     

Rabeprazole, amoxycillin and low- or high-dose clarithromycin for cure of Helicobacter pylori infection

BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. RESULTS: There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.     

Metronidazole containing quadruple therapy for infection with metronidazole resistant Helicobacter pylori: a prospective study

BACKGROUND: Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy). AIM: To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States. METHODS: Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d. RESULTS: A total of 26 patients were entered into the study; 22 for their first treatment and four as re-treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78-99%). Both treatment failures reported full compliance to 14 days of therapy. Side-effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate. CONCLUSION: Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice-a-day combination therapies.     

四联疗法治疗幽门螺杆菌阳性消化性溃疡疗效观察

目的观察四联疗法治疗HP阳性的十二指肠溃疡、胃溃疡HP根除率及疗效。方法经胃镜和快速尿素酶方法确诊的HP阳性十二指肠溃疡和胃溃疡共247例。予雷贝拉唑20 mg,2次/日+胶体果胶铋0.2,2次/日+克拉霉素0.5,2次/日+甲硝唑0.4,2次/日,口服一周,继而连服雷贝拉唑20 mg,一次/日共5周。疗程结束四周后胃镜及快速尿素酶试验复查。结果随访成功196例,HP总根除率81.6%,其中十二指肠溃疡根除率86%,胃溃疡根除率67.4%,溃疡病总有效率88.3%,其中十二指肠溃疡有效率89.3%,胃溃疡有效率84.8%,两组比较差异显著(P0.01)。结论含雷贝拉唑的四联疗法,对HP阳性的十二指肠溃疡HP根除及疗效优于HP阳性的胃溃疡。     

Sequential therapy using high-dose esomeprazole-amoxicillin followed by gatifloxacin for Helicobacter pylori infection

BACKGROUND: The success rate of current anti-Helicobacter pylori triple therapies in now generally 80% or less. Sequential therapy has proved superior. AIM: To test a new sequential therapy for H. pylori eradication. METHODS: This was a pilot study of a sequential therapy consisting of 40 mg of esomeprazole and 1 g amoxicillin t.d.s., for 12 days. On days 6 through 12 gatifloxacin (400 mg in the morning) was added. Outcome was accessed 4 or more weeks after ending antibiotic therapy. Both naive and treatment failures were eligible. RESULTS: Thirty patients were entered in the study. One was lost to follow-up and one stopped early because of side effects. The success rate intention-to-treat was 80% (95% CI: 61-92%). The per-protocol eradication rate was 85.7% (95% CI: 67-95%); two of the four failures had pre-treatment gatifloxacin-resistant H. pylori. Side effects were reported by 13 patients (46%) and were generally mild with diarrhoea being most common (n = 6). Only one patient stopped medicine because of side effects of dizziness (severe) and diarrhoea (mild). CONCLUSIONS: Sequential therapy using the combination of a high dose of proton-pump inhibitor and amoxicillin followed gatifloxacin was effective, but pre-treatment susceptibility testing may become necessary as fluoroquinolone resistance increases.     

秘剂四联疗法与序贯疗法治疗幽门螺杆菌感染的Meta分析

目的 系统评价10天秘剂四联疗法和10天序贯疗法治疗中国患者幽门螺旋杆菌(Hp)感染的疗效和安全性。方法 利用中英文数据库,查找使用两种方案治疗中国患者Hp感染患者的随机对照实验(RCT)。根据纳入排除标准选取研究,提取资料,并使用Jadad量表评价研究质量,采用STATA12统计软件进行Meta分析。结果 纳入14项RCT研究,1518名患者,秘剂四联疗法和序贯疗法的Hp清除率按意向分析(ITT)分别为82.75%和84.13 %(RR = 0.99(0.95,1.04),P=0.658),两种疗法Hp根除率方面的差异无统计学意义。秘剂四联疗法与序贯疗法的不良反应发生率分别是14.19%和12.45 %(RR = 1.30(0.99,1.69),P=0.056),不良反应发生率差异也无统计学意义。结论 当前证据表明,10天铋剂四联疗法和10天序贯疗法治疗中国患者Hp感染的疗效和安全性相当,可以作为中国患者的一线治疗方案。     

泮托拉唑四联4d与7d疗法随机对照研究

目的:比较泮托拉唑四联4d疗法和7d疗法的幽门螺杆菌(Hp)根除率和症状缓解率.方法:Hp阳性的胃炎、胃溃疡或十二指肠溃疡患者随机接受4d或7d泮托拉唑四联疗法:泮托拉唑40mg、克拉霉素250mg、阿莫西林1.0g和胶体枸橼酸铋钾220mg,均为bid.根除治疗4周后复查Hp是否根除,了解症状缓解情况.结果:共有73例患者纳入本试验,其中4d组37例,7d组36例.4d组Hp根除率为62.2%[意向治疗(ITT)群组分析和符合方案(PP)群组分析],7d组Hp根除率为83.3%(ITT)和88.2% (PP);4d组疼痛缓解率为78.8%(ITT,PP),7d组疼痛缓解率为83.9%(ITT)和89.7%(PP).按PP群组分析4d组Hp根除率明显低于7d组,按ITT群组分析,2组方案Hp根除率无明显差异.2组方案疼痛缓解率无明显差异,2组患者均未出现严重不良反应.结论:泮托拉唑四联4d疗法可以获得较高的疼痛缓解率,但是其Hp根除率低于7d疗法,不宜作为Hp根除治疗的一线治疗方案.     

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.