Dual therapy versus triple therapy forHelicobacter pylori-associated duodenal ulcers

We compared the ulcer healing effect and eradication ofH. pylori by one-week triple therapy of bismuth, metronidazole, and tetracycline with two-week dual therapy of amoxicillin and omeprazole. One hundred twelve patients with confirmedH. pylori infection and duodenal ulcers were recruited in a prospective, randomized, single-blinded trial. Ulcer healing, eradication ofH. pylori in the stomach six weeks after randomization, and side effects reported by patients during the therapy. Duodenal ulcers were healed in 44 of 49 (89.8%, 95% CI 81.3–98.3%) patients receiving triple therapy and in 44 of 53 (83.0%, 95% CI 72.9–93.1%) patients receiving dual therapy (P=0.32).H. pylori was successfully eradicated in 41 of 49 (83.6%, 95% CI 73.4–94%) patients and in 40 of 53 (75.5%, 95% CI 63.9–87.1%) patients in the triple therapy group and the dual therapy group respectively (P=0.31). Side effects experienced by patients who received triple therapy were significantly more frequent than those who received dual therapy (P=0.0076). In conclusion, a two-week course of omeprazole and amoxicillin achieves a comparable rate ofH. pylori eradication and ulcer healing with fewer side effects.     

潘托拉唑三联疗法与奥美拉唑三联疗法治疗幽门螺杆菌相关性消化性溃疡

目的：研究潘托拉唑治疗消化性溃疡及根除幽门螺杆菌（HP）的疗效和安全性。方法：将经过胃镜和病理学检查证实了的消化性溃疡患者随机分成潘托拉唑组（治疗组）和奥美拉唑组（对照组）。其中治疗组60例,应用潘托拉唑、羟氨苄青霉素和甲硝唑治疗;对照组57例,应用奥美 拉唑、羟氨苄青霉素和甲硝唑治疗。停药后均复查胃镜观察溃疡愈合情况以及HP根除情况。结果：两组胃溃疡的愈合率分别为92．3％和95．4％,HP根除率分别为92．3％和90．9％;十二指肠溃疡的愈合率分别为97．1％和94．3％,HP根除率分别为91．2％和94．3％,两组比较差异无显著性（P＞0．01）,各项症状的改善情况两组相似（P＞0．1）。治疗期间两组均有良好的耐受性。结论：潘托拉唑对消化性溃疡有很高的治愈率,以它为主的三联疗法可达到很高的HP根除率,对消化性溃疡的疗效与奥美拉唑相当,不良反应极少,患者耐受性,依从性好,是一种有广泛应用前景的新型质子泵抑制剂。     

Evaluation of three different proton pump inhibitors with amoxicillin and metronidazole in retreatment for Helicobacter pylori infection

GOALS: We compared the eradication results of retreatment of eradication with proton pump inhibitor (PPI) plus amoxicillin and metronidazole for patients with Helicobacter pylori infection not eradicated by initial treatment with PPI plus amoxicillin and clarithromycin. BACKGROUND: In Japan, the guideline proposes that the use of metronidazole in a triple therapy containing PPI, PPI plus amoxicillin and metronidazole is desirable in retreatment. However, there are no reports comparing various retreatment using different PPIs. METHODS: After initial treatment failure with a PPI plus amoxicillin and clarithromycin, 169 patients were randomized to a PPI (rabeprazole, lansoprazole, or omeprazole) plus amoxicillin and metronidazole given b.i.d. for 7 days. RESULTS: Pretreatment susceptibility testing showed a high level of clarithromycin resistance (78%). The over all eradication rates were similar with the 3 PPIs, 91.1% range 90.1 to 91.4 with intention-to-treat analysis. The presence of metronidazole resistance reduced the eradication rate by approximately 40% (from 96.6% to 57.1%, P<0.05). CONCLUSIONS: In Japan, the combination of a PPI plus amoxicillin and metronidazole provide excellent eradication rates after initial treatment failure with a PPI plus amoxicillin and clarithromycin. The results with metronidazole resistant strains are less satisfactory and pretreatment susceptibility testing may become needed if the prevalence of metronidazole resistant H. pylori increase.     

Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate,metronidazole, and tetracycline given with omeprazole versus omeprazole,amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective,randomized, multicenter,North American trial

OBJECTIVES: This multicenter, randomized, active-controlled trial assessed efficacy of bismuth-based quadruple therapy with omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline (OBMT) using a single-triple capsule of BMT compared with triple therapy with omeprazole, amoxicillin, and clarithromycin (OAC) in treatment of patients with Helicobacter pylori infection and duodenal ulcers. METHODS: Patients with active duodenal ulcer or diagnosed within the past 5 yr and with infection documented by (13)C-urea breath test plus histology or culture were randomly assigned to 10-day course of OBMT using a single-triple capsule containing bismuth biskalcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg given as three capsules q.i.d. with omeprazole 20 mg b.i.d., or a 10-day course of OAC, omeprazole 20 mg plus amoxicillin 1 g plus clarithromycin 500 mg, all b.i.d. Eradication was confirmed by two negative urea breath tests at >1 month and >2 months after therapy. RESULTS: One hundred thirty-eight patients received OBMT and 137 OAC. Modified intent-to-treat eradication rates were 87.7% for OBMT and 83.2% for OAC (95% CI = -3.9%-12.8%; p = 0.29). OBMT eradicated 91.7% metronidazole-sensitive and 80.4% metronidazole-resistant strains (p = 0.06). OAC eradicated 92.1% clarithromycin sensitive and 21.4% clarithromycin-resistant strains (p < 0.001). Adverse events occurred in 58.5% of OBMT patients and 59.0% of OAC patients. CONCLUSIONS: OBMT regimen using the single-triple capsule is as efficacious and well-tolerated as the widely used OAC regimen for H. pylori eradication. This OBMT therapy largely overcomes H. pylori metronidazole resistance, present in 40% of patients in this study.     

Effectiveness of 10 day-sequential therapy for Helicobacter pylori eradication in Korea

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. Proton pump inhibitor (PPI)-based triple therapy is the most preferred regimen in clinical practice. However, a critical fall in the H. pylori eradication rate has been observed in the recent years. A novel 10 day-sequential therapy consists of five days of dual therapy followed by five days of triple therapy regimen has recently been described. We aimed to evaluate whether 10 day-sequential therapy eradicated H. pylori infection better than the PPI-based triple therapy in Korea. METHODS: 158 patients with proven H. pylori infection were randomized to receive either 10 day-sequential therapy (20 mg of omeprazole, 1.0 g of amoxicillin, each administered twice daily for the first 5 days, followed by 20 mg of omeprazole, 500 mg of clarithromycin, 500 mg of metronidazole, each administered twice daily for the remaining 5 days) or PPI-based triple therapy (20 mg of omeprazole, 1.0 g of amoxicillin, 500 mg of clarithromycin, each administered twice daily for 1 week). Outcome of eradication therapy was assessed 8 weeks after the cessation of treatment. RESULTS: Eradication rates of 10 day-sequential therapy and PPI-based triple therapy were 77.9% (60/77) and 71.6% (58/81) by intention to treat analysis, respectively (p=0.361). By per protocol analysis, eradication rates of 10 day-sequential therapy and triple therapy were 85.7% (60/70) and 76.6% (58/76), respectively (p=0.150). There were no significant differences in adverse event rates and treatment compliance between two groups. CONCLUSIONS: The 10 day-sequential therapy regimen failed to achieve significantly higher eradication rates than PPI-based triple therapy.     

The Influence of Drug Dosage on Helicobacter pylori Eradication: A Cost-Effectiveness Analysis

Objectives: This review provides an updated overview on Helicobacter pylori (HP) trials, focusing on drug dosage and cost: benefit ratio. Methods: Literature review, with analysis of 362 treatments with 13,562 patients. Results: Statistical evaluation demonstrated the following mean HP eradication rates (ER): 11.7% for mono-therapy, 50.7% for dual therapy without acid suppression, 59.8% for dual therapy including acid suppression, 78.1% for triple therapy without acid suppression, 77.5% for triple therapy including acid suppression, and 89.1% for multiple combination therapy (differences between all groups, p < 0.001). In dual therapy, omeprazole/amoxicillin or clarithromycin (mean ER 65.9 vs. 67.6%, NS) showed better results than other combinations. Favorable results in triple therapy were achieved by combined bismuth/imidazoles/tetracycline or by omeprazole/imidazoles/amoxicillin or clarithromycin (mean ER 83.4 vs. 83.5% vs. 93%, NS). The best mean eradication rate, 93.5%, was attained with omeprazole/bismuth/imidazoles/tetracycline. Subgroup analysis revealed a significant correlation between the dose/ duration of therapy and the ER for most combinations. The best cost: benefit ratio was demonstrated for omeprazole/imidazoles/clarithromycin (triple therapy including acid suppression). Conclusions: The optimal cost; benefit ratio will be achieved by treatment for 1 wk with omeprazole (20 mg/day), imidazoles (such as metronidazole 2 × 400 mg/day), and clarithromycin (2 × 250 mg/day). If dual therapy is taken into account in terms of simplicity and few side effects, the treatment success in the combination of omeprazole (≤ 2 × 20 mg/day) and amoxicillin (≤ 2 g/day) or clarithromycin (≤ 1 g/day), each given for 2 wk, is highly dependent on optimal drug dosage.     

Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance

AIM To evaluate the efficacy of antimicrobial susceptibilityguided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance.METHODS A total of 1034 patients infected by Helicobacter pylori(H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034(15%) patients showed resistance to two(127/1034; 12%) and to three(30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori-resistance(clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL(omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43cases, OAM(omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC(omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori-resistance(clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR(omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. RESULTS Intention-to-treat eradication rates were: OAL(97.6%), OAM(91.6%), OAC(92.3%) and OAR(58.3%). Cure rate was significantly higher in na?ve patients treated with OAR-10 compared to patients who had two or three previous treatment failures(83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. CONCLUSION Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.     

Azithromycin in a triple therapy for H.pylori eradication in active duodenal ulcer

AIM：To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole,which is still widely used in Russia,andB)azithromycin amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication.METHODS:100 patients with active duodenal ulcer were includid in the open,multicentre,randomized study with comparative groups.Patients were randomly assigned to one of the following one-week triple regimes:A)metronidazole500mg bid,amoxicillin1gbid and omeprazole 20mg bid(OAM,n=50)andB)azithromycin1g od for the first3days(total dose3g).amoxicillin 1g bid and first 3days(total dose3g).amoxicillin 1g bid and omeprazole20mg bid(OAA,n=50).Omeprazole 20mg od was given after the eradication course as a monotherapy for three weeks ,The control endoscopy was performed8 weeks after the entry,H.pyloriinfection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test.RESULTS:97 patients completed the study according to the protocol(1patient of the OAM group did not come to the control endoscopy.2patients of the OAA group stopped the treatment because of mild allergic urticaria).Duodenal ulcers were healed in48patients of the OAM group(96%;CI90.5-100%)and in 46patients of the OAAgroup(92%;CI89.5-94.5%)(p=ns).H.pylori infection was eradicated in 15out of 50patients with OAM(30%;CI17-43%)and in36out of 50patients treated with OAA(72%,CI59-85%)(P&lt;0.001)-IПanalysis.CONCLUSION:The triple therapy with omeprazole,amoxicillin and metronidazole failed to eradicateH.pylori in the majorty of patients,which is an essential argument to withdraw this regimen out of the national recommendations,Macrolide with amoxicillin are preferable to achieve higher eradication rates.Azitromycin(1g od for the first3days)can be considered as a successful component of the triple PPI-based regimen.     

Evaluation of triple and quadruple Helicobacter pylori eradication therapies in Iranian children: a randomized clinical trial

BACKGROUND: Clinical trials in children concerning Helicobacter pylori eradication treatments are scarce. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapy using PPI, amoxicillin and clarithromycin in Iranian children. We also evaluated the efficacy of quadruple therapy with PPI, metronidazole, amoxicilin and bismuth citrate in Iranian children. METHODS: This was a randomized clinical trial performed in Emam Khomeini Hospital between 2003 and 2004. Patients with confirmed H. pylori infection by histology were divided into two groups in a randomized 1:1 scheme: the triple regimen group (omeprazole, clarithromycin and amoxicillin for 10 days) and the quadruple regimen group (omeprazole, amoxicillin, metronidazole and bismuth citrate for 10 days). The eradication was assessed by the C-urea breath test 4 weeks after the end of treatment and analyzed by per-protocol and intention-to-treat approaches. RESULTS: One hundred and twenty-two patients (mean age 12.36+/-3.06 years) were entered into the study. Only 100 patients completed the study (50 patients in each regimen group). The eradication rates by triple therapy were 92% and 75.5% for the "per-protocol" and "intention-to-treat" approaches, respectively. In the quadruple regimen group, the eradication rates were 84% by the per-protocol approach and 68.8% in the intention-to-treat approach. Symptom responses to therapy were reported in all patients with successful eradication (88% of all patients). CONCLUSION: With regard to recent recommendations, we also suggest PPI, amoxicillin and clarithromycin triple therapy as a first-line eradication treatment, and quadruple therapies as a second-line option, in Iranian children.     

Triple Therapy vs. Amoxicillin Plus Omeprazole for Treatment of Helicobacter pylori Infection: A Multicenter, Prospective, Randomized, Controlled Study of Efficacy and Side Effects

Objective : this study compares the efficacy and side effects of the two commonly used treatment regimens for Helicobacter pylori infection. Methods : 118 patients with culture-proven H. pylori infection (61 with duodenal ulcer, 19 with gastric ulcer, three with both duodenal and gastric ulcer, and 35 with non-ulcer dyspepsia) were randomized to receive either triple therapy (tetracycline 250 mg, metronidazole 250 mg, colloidal bismuth subcitrate 120 mg, four times daily) for 14 days or amoxicillin 1000 mg and omeprazole 40 mg both twice daily for 14 days. The isolated H. pylori strain was metronidazole susceptible in 93%. Antral biopsy samples were taken for culture, urease testing, histology and, in most patients, for PCR at least 6 wk after treatment. A separate corpus sample was taken for culture. Eradication was defined as the absence of H. pylori in all specimens. In seven cases, when only histology was doubtfully positive, and all other tests including PCR were negative, a ¹³C-urea breath test was performed, the result of which was considered conclusive. Severity of the side effects was recorded by the patient on a semi-quantitative scale. Results: H. pylori was eradicated by triple therapy in 96.3% and by amoxicillin/omeprazole in 77.2% of the patients ( p = 0.008). Side effects occurred more often with triple therapy (72.7% vs. 50.8 %; p < 0.05) but were mild in most cases. Severe side effects occurred equally in both treatment groups. Conclusions : When the prevalence of metronidazole resistance is low, triple therapy is more effective than amoxicillin/omeprazole. Side effects occur more often in triple therapy but are mild in most cases.     

Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori (H pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H pylori and ulcer healing in Chinese peptic ulcer patients. METHODS: A total of 103 subjects with Hpylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1 000 mg and either clarithromycin 500 mg (OAC group, n = 58) or metronidazole 400 mg (0AM group, n - 45). All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H pylori. Successful eradication was defined as negative results from both examination methods. RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in 0AM group. Based on the intention-to-treat analysis, the eradication rate of H pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in 0AM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21) in 0AM group (per-protocol analysis, P>0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%) reported adverse events (P>0.05). CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H pylori infection in China.     

Effect of omeprazole and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the healing of duodenal ulcer: comparison with a historical control.

BACKGROUND/AIMS: To test the hypothesis of equivalence of an omeprazole 7-day triple therapy without subsequent acid suppression and a historical ranitidine 12-day triple therapy (recruiting phase 1989-91) with subsequent acid suppression in their effect on the eradication of Helicobacter pylori (H. pylori) and the healing of duodenal ulcer. METHODOLOGY: Seventy-seven patients with H. pylori-positive duodenal ulcers received a 7-day treatment with amoxicillin 750 mg tid and metronidazole 500 mg tid. Additional omeprazole 20 mg or 40 mg once daily was given to 39 and 38 of the patients, respectively. Endoscopy was performed before treatment and four weeks after cessation of therapy. RESULTS: The cumulative intention-to-treat (ITT) H. pylori-eradication rate was 66% (51/77) as compared to 89% (46/52) for the historical control (p < 0.05). The corresponding ulcer healing rates were 90% (69/77) and 92% (48/52). Primary metronidazole resistance (PMR) had escalated from 10% to 27% within 6 years resulting in eradication rates of 84% for sensitive and 19% for resistant strains (p < 0.001). PMR could be demonstrated in 45% of all female, but only in 17% of the male patients (p < 0.05). In the patients with H. pylori eradication, the ulcers healed in 98% (50/51) as compared to 73% (19/26) in those with persistent infection (p < 0.005). Analysis based on the presence of PMR showed ulcer healing rates of 95% (53/56) for sensitive and 76% (16/21) for resistant strains (p < 0.05). Improvement of pain also showed a significant correlation with successful eradication. H. pylori-eradication, healing and symptom relief were similar in the omeprazole 20 mg and 40 mg groups. CONCLUSIONS: The effect of amoxicillin plus metronidazole plus antisecretory agent on the eradication of H. pylori has decreased markedly during the past 6 years due to the escalation of PMR. Doubling of the omeprazole dose does not affect outcome. Cure of the infection as well as metronidazole susceptibility enhance duodenal ulcer healing and symptom relief. Acid suppression following a successful 1-week anti-HP therapy is not required for duodenal ulcer treatment.     

Prevalence of resistance to clarithromycin and its clinical impact on the efficacy of Helicobacter pylori eradication.

BACKGROUND: Triple therapy with a proton-pump inhibitor (PPI) in combination with metronidazole and clarithromycin is the method of choice for eradication of Helicobacter pylori. Failures have been primarily blamed on the development of resistance to clarithromycin. The present study investigated the prevalence and clinical significance of resistance to clarithromycin and metronidazole in determining therapeutic success of both triple therapy as a primary eradication method and high-dose dual therapy in non-responders. METHODS: On the basis of prior therapy, H. pylori-positive patients were assigned to one of two groups in the present prospective study. Group A (n = 93) included patients who had not undergone any prior eradication treatment, whereas group B (n = 15) consisted of patients who had received clarithromycin but in whom eradication had been unsuccessful. All patients underwent endoscopy with biopsy for bacterial culture and resistance studies. Patients in group A were treated with a 7-day regimen of pantoprazole (40 mg twice daily), metronidazole (500 mg twice daily), and clarithromycin (250 mg twice daily), whereas those in group B received omeprazole (40 mg three times a day) and amoxycillin (1000 mg three times a day ) for 14 days. Success of the eradication treatment was ascertained by means of the 13C urea breath test. RESULTS: In group A resistance to clarithromycin and metronidazole was identified in 3 patients (4.9%) and in 14 patients (22.9%), respectively. Eradication proved successful in 78 of 84 patients (92.6%) followed up. Two of the 3 patients with primary clarithromycin resistance and 1 of the 14 patients with metronidazole resistance did not respond to treatment. In group B isolated or combined resistance to clarithromycin was found in seven patients, whereas another four showed isolated resistance to metronidazole. Eradication proved successful in 10 of 13 controlled patients (76.9%) followed up, and only 2 patients reported severe side effects. CONCLUSION: Determination of antibiotic resistance before initiating therapy is not necessary, since primary resistance to clarithromycin is rare. The Italian triple therapy remains a highly effective primary therapeutic method. Further, routine determination of resistance in non-responders also seems to be superfluous because high-dose dual therapy is an effective and well-tolerated second-line therapy regardless of the patients' resistance status.     

Helicobacter pylori eradication versus one-year maintenance therapy: effect on relapse and gastritis outcome.

OBJECTIVE: The aim of this study was to determine ulcer healing and H. pylori eradication rates obtained with triple therapy (omeprazole, amoxicillin and clarithromycin). Ulcer relapsing rate one year after eradication was also assessed. Maintenance therapy with placebo was compared with ranitidine therapy and the effect of eradication on histological variables of the gastric mucosa was studied. METHODS: A prospective, double-blind parallel study was performed in 85 patients endoscopically diagnosed of duodenal ulcer H. pylori positive. Patients were randomized to a 7-days triple therapy (group A) or omeprazole plus antibiotic placebo (group B). All patients were treated only with omeprazole for the next three weeks. Patients with ulcer healing after treatment were entered in a one-year follow up phase with ranitidine placebo (group A) or ranitidine (group B). Endoscopy and biopsies were performed at baseline, after treatment (5 weeks) and after 12 months of follow-up or when relapsing symptoms appeared. RESULTS: Healing rate was 90.2% in group A and 85.7% in group B. Eradication rate was 78% in group A and 0% in group B. Out of 37 healed patients in group A, eradication was achieved in 29 and only one relapse was found (3.4%). Three out of eight patients with healing but without eradication relapsed at 12 months (35%) (p < 0.05). Histopathological results showed statistically significant differences (p < 0.05) between eradicated and non eradicated patients in terms of severity of inflammation and intestinal metaplasia, but not in terms of atrophy. CONCLUSIONS: H. pylori eradication is useful to prevent ulcer relapse and to improve gastric mucosa status.     

A prospective randomized study of amoxycillin and omeprazole with and without metronidazole in the eradication treatment of Helicobacter pylori

A combination of amoxycillin and omeprazole is often used to treat Helicobacter pylori infection. A three-drug regimen comprising metronidazole, amoxycillin and omeprazole has been proposed as an alternative therapy. In a prospective, randomized, comparative study, we evaluated these two regimens with respect to safety and ef?cacy in patients with H. pylori infection. Sixty patients with peptic ulcer (gastric, 32 patients; duodenal, 28 patients) who had a history of ulcer recurrence were randomly assigned to dual therapy with amoxycillin (500 mg three times daily for 2 weeks) and omeprazole (20 mg once daily for 8 weeks) or to triple therapy with metronidazole (500 mg twice daily for 2 weeks) plus amoxycillin and omeprazole, given in the same dosages as dual therapy. Forty-eight patients completed the protocol; treatment was discontinued because of side effects in nine patients, and three patients dropped out of the study. On the basis of all patients treated, the rate of H. pylori eradication was signi?cantly higher for triple therapy 20/23 cases, 87.0%; 95% con?dence interval (CI), 0.664–0.972) than for dual therapy 13/25, 52.0%; 0.313–0.722; P < 0.05). On an intention-to-treat basis, the difference between the groups in the rate of H. pylori eradication was marginally signi?cant (P= 0.06 [0.028–0.512]). Side effects were reported by ?ve patients receiving triple therapy (skin rash, one; nausea, two; headache, one; abdominal pain, one), and four patients receiving dual therapy (skin rash, two; abdominal pain, one; diarrhoea, one). All side effects resolved spontaneously after termination of treatment. There was no signi?cant difference in safety between the two regimens. Triple therapy with metronidazole, amoxycillin, and omeprazole was signi?cantly more effective for the eradication of H. pylori than dual therapy with amoxycillin and omeprazole alone. The safety of these regimens was similar, and triple therapy was found to be clinically acceptable.     

Comparison of short- and long-term treatment protocols and the results of second-line quadruple therapy in children with <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

BACKGROUND: Research regarding the optimal therapeutic approach to Helicobacter pylori infection in children is ongoing. There is no consensus as to duration of treatment or second-line therapy. The purpose of this study was compare the efficacy of 7-day and 14-day triple therapies and report the results of second-line quadruple therapy in children. METHODS: A total of 275 consecutive H. pylori-infected patients were enrolled into two groups. Group 1 (n = 180) received triple therapy with 14 days of amoxicillin and clarithromycin and 21 days of proton pump inhibitor. Group 2 (n = 95) received triple therapy including 7 days of amoxicillin and clarithromycin with 21 days of proton pump inhibitor. Subsequently, 89 patients not responding to the triple therapies received quadruple therapy comprising omeprazole (14 days), bismuth subcitrate (7 days), doxycycline (7 days), and metronidazole (7 days). Eradication was evaluated by 13C-urea breath test. RESULTS: The per-protocol eradication rates in groups 1 and 2 were 60.5% and 55.8%, respectively (P = 0.44). In the second interview with 227 patients, severe symptoms were reported to have disappeared in 59% and decreased notably in 34.8%. Helicobacter pylori was eradicated in 66.7% of patients at the end of the quadruple therapy. In the third interview with 75 patients, severe symptoms had decreased in 38.6% and disappeared in 56%. CONCLUSIONS: The different duration of the two treatment regimens had no impact on eradication rates. Furthermore, quadruple therapy was necessary to achieve H. pylori eradication after triple therapy. However, the eradication rate with quadruple therapy was still insufficient. Consequently, a new therapeutic approach to H. pylori infection in children is needed.     

Concomitant therapy achieved the best eradication rate for Helicobacter pylori among various treatment strategies

AIM: To compare the Helicobacter pylori(H.pylori) eradication rate of clarithromycin-based triple therapy,metronidazole-based triple therapy,sequential therapy and concomitant therapy.METHODS: A total of 680 patients infected with H.pylori were divided into 4 groups and each group was treated with a different eradication therapy.Clarithromycin-based triple therapy was applied to the first group [rabeprazole,amoxicillin and clarithromycin(PAC) group: proton pump inhibitor(PPI),amoxicillin,clarithromycin],whereas the second group was treated with metronidazole-based triple therapy [rabeprazole,amoxicillin and metronidazole(PAM) group: PPI,amoxicillin,metronidazole].The third group was treated with rabeprazole and amoxicillin,followed by rabeprazole,clarithromycin and metronidazole(sequential group).The final group was simultaneously treated with rabeprazole,amoxicillin clarithromycin and metronidazole(concomitant therapy group).In the case of a failure to eradicate H.pylori,second-line quadruple and third-line eradication therapies were administered.RESULTS: The per protocol(PP) analysis was performed on 143,139,141 and 143 patients in the PAC,PAM,sequential and concomitant groups,respectively.We excluded patients who did not receive a C13-urea breath test(22,20,23 and 22 patients,respectively) and patients with less than an 80% compliance level(5,11,6 and 5 patients,respectively).The eradication rates were 76.2%(109/143) in the PAC group,84.2%(117/139) in the PAM group,84.4%(119/141) in the sequential group and 94.4%(135/143) in the concomitant group(P = 0.0002).All 14 patients who failed second-line therapy were treated with thirdline eradication therapy.Among these 14 patients,6 infections were successfully eradicated with the thirdline therapy.Both PP and intention-to-treat analysis showed an eradication rate of 42.9%(6/14).In the PAC group,3 of 4 patients were successfully cured(3/4,75%); 2 of 2 patients in the PAM group(2/2,100%) and 1 of 5 patients in the sequential group(1/5,20%) were also cured.In the concomitant group,all 3 patients failed(0/3,0%).CONCLUSION: The eradication rate for the concomitant therapy was much higher than those of the standard triple therapy or sequential therapy(Clinical Trials.gov number NCT01922765).     

Relationship between eradication therapy and clarithromycin-resistant Helicobacter pylori in Japan

Since clarithromycin is expected to be widely used to treat Helicobacter pylori infection in the near future, it is important to investigate the relationship between resistance to clarithromycin and the regimens of eradication therapy. We investigated: (1) the usefulness of susceptibility tests prior to eradication therapy, and (2) the rate of acquisition of H. pylori resistance to clarithromycin after treatment failure. Drug susceptibility tests to clarithromycin and amoxicillin were conducted by Dry Plate Test or E-test. The subjects in the first part of this study included 112 patients with H. pylori infection who received triple therapy with various combinations of drugs, including clarithromycin. The eradication rate in patients with clarithromycin-susceptible H. pylori was significantly higher than that in patients with clarithromycin-resistant H. pylori. The second part of this study included 21 patients in whom H. pylori was not eradicated by triple therapy and 12 patients in whom H. pylori was not eradicated with dual therapy including clarithromycin. Of the 33 patients showing non-eradication. 90.9% of those treated with dual therapy and 35.7% of those treated with triple therapy acquired secondary resistance of H. pylori to clarithromycin. We conclude that it is important to conduct drug susceptibility tests prior to treatment of H. pylori infection. Since the incidence of acquiring clarithromycin resistance was significantly higher in the patients showing non-eradication, it is important to choose a regimen with a higher eradication rate, such as triple therapy.     

Cost-Effectiveness of Treatment Regimens for the Eradication of Helicobacter pylori in Duodenal Ulcer

Background: Eradication of Helicobacter pylori with antimicrobials was recommended by a recent NIH consensus panel for all infected patients with peptic ulcer disease. The precise regimen that should be used for eradication of the infection remains uncertain because of the variety of regimens described, variable results with the regimens, and difficulties in predicting drug compliance outside clinical trials. Methods: A decision analysis tree was developed with three regimens that are widely used regimens for the eradication of H. pylori: 1 ) 2-wk triple drug therapy (metronidazole, bismuth, tetracycline with H2 receptor antagonist), 2) 2-wk omeprazole and amoxicillin, and 3) 2-wk omeprazole and clarithromycin. Traditional H2 receptor antagonist therapy was used for comparison. A 2-yr time period was chosen for study to allow sufficient time for relapse and to evaluate its effect on the treatment strategy. Probabilities for eradication, compliance, and metronidazole resistance were determined from published data, and assumptions were tested by sensitivity analysis. Results: Standard 2-wk triple drug therapy was the least expensive strategy ($720), and conventional H2 receptor antagonist therapy was the most expensive ($1791). Costs with 2-wk therapy with omeprazole and clarithromycin ($768) were lower than with omeprazole and amoxicillin ($1028). Conclusions. Treatment to eradicate H. pylori in infected patients with duodenal ulcer is a less expensive strategy than traditional therapy with H2 receptor antagonists. Triple drug therapy is the optimal regimen in areas where metronidazole resistance rates are <36% and compliance is >53%. Omeprazole and amoxicillin is not cost-effective unless eradication rates are greater than 74%. Dual drug therapy with omeprazole and clarithromycin is effective in regions where metronidazole resistance is high or where it is anticipated that there would be poor compliance with the more complicated triple drug therapy regimen.     

Triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H pylori eradication： A comparative three-armed randomized clinical trial

AIM: To compare the effectiveness of triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H pylori eradication in a comparative threearmed randomized clinical trial. METHODS: A total of 360 H pylori-positive patients suffering from dyspepsia and aging 24-79 years with a median age of 42 years were enrolled in the study and randomly allocated into the following three groups: group A (n = 120) received a standard 1-wk triple therapy (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 500 mg clarithromycin b.i.d.); group B (n = 120) received a 10-d standard quadruple therapy (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 240 mg colloidal bismuth subcitrate b.i.d., and 500 mg metronidazole b.i.d.); group C (n = 120) received the new protocol, i.e. 375 mg sultamicillin (225 mg ampicillin plus 150 mg sulbactam) b.i.d. (before breakfast and dinner), instead of amoxicillin in the standard quadruple therapy for the same duration. Chi-square test with the consideration of P < 0.05 as significant was used to compare the eradication rates by intention-to-treat and per-protocol analyses in the three groups. RESULTS: The per-protocol eradication rate was 91.81% (101 patients from a total of 110) in group A, 85.84% (97 patients from a total of 113) in group B, and 92.85% (104 patients from a total of 112) in group C. The intentionto-treat eradication rate was 84.17% in group A, 80.83% in group B, and 86.67% in group C. The new protocol yielded the highest eradication rates by both per-protocol and intention-to-treat analyses followed by the standard triple and quadruple regimens, respectively. However, the differences were not statistically significant between the three groups. CONCLUSION: The results of this study provide further support for the equivalence of triple and quadruple therapies in terms of effectiveness, compliance and side-effect profile when administered as first-line treatment for H pylori infection. Moreover, the new protocol using ampicillin-sulbactam instead of amoxicillin in the quadruple regimen is a suitable first-line alternative to be used in regions with amoxicillin-resistant H pylori strains.