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.     

A randomized comparison of four omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia

BACKGROUND: Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe. This study evaluated alternative eradication regimens. METHODS: Helicobacter pylori-positive patients (n=323) with non-ulcer dyspepsia were randomized to receive one of four 1-week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d. (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d. (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d. (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2-5 (OAAz). Eradication was confirmed by urea breath test 4-6 weeks after treatment. Susceptibility testing was performed in the case of eradication failure. RESULTS: The eradication rate with OAAz was 38% (95% CI, 25.6-49.4) on intention-to-treat analysis, which was lower (P < 0.05) than with the other regimens [OCM, 61% (50.0-72.8); OBC, 65% (54.0-76.5); OAC, 72% (61.8-81.8)]. Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant. CONCLUSIONS: OAC remains the reference treatment for H. pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin. Susceptibility testing should be considered after unsuccessful eradication therapy.     

Comparison of two 3-day Helicobacter pylori eradication regimens with a standard 1-week regimen

BACKGROUND: The duration of Helicobacter pylori eradication regimens has decreased to 1 week with cure rates of over 90%. This can be attributed to the use of triple drug regimens including potent inhibitors of gastric acid secretion and clarithromycin. There is no theoretical reason why shorter regimens should not be possible. AIM: To compare two 3-day, low-dose, twice daily regimens with 1 week of omeprazole 20 mg b.d., clarithromycin 250 mg b.d., and metronidazole 400 mg b.d. (OCM) METHODS: Outpatients referred for gastroscopy were screened by biopsy urease test. H. pylori-positive patients were randomized to receive either lansoprazole 30 mg b.d., tri-potassium dicitrato bismuthate one tablet b.d., clarithromycin 250 mg b.d., and amoxycillin 1 g b.d. for 3 days (LTdbCA), or ranitidine bismuth citrate 400 mg b.d., clarithromycin 250 mg b.d. and amoxycillin 1 g b.d. for 3 days (RbcCA) or omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. for 1 week (OCM). They were not pre-treated with a gastric acid inhibitor. After 8 weeks, H. pylori status was assessed by 13C urea breath test. RESULTS: 974 out of 1114 patients referred for gastroscopy were screened by biopsy urease test. 140 patients were not screened either because they were anticoagulated or for technical reasons. 334 patients were H. pylori-positive: 154 were excluded mostly because of allergy to penicillin and personal reasons but 180 were randomized to treatment All regimens were well tolerated. For LTdbCA (n=60), RbcCA (n=59), and OCM (n=61) the H. pylori cure rates (95% CI) were 23% (12-34), 14% (5-23) and 87% (79-95), respectively, using intention-to-treat analysis and 25% (14-36), 15% (6-24) and 88% (80-96), respectively, if analysed per protocol. OCM was significantly superior to LTdbCA and RbcCA (P < 0.001) but there was no significant difference between regimens LTdbCA and RbcCA. CONCLUSIONS: OCM is an extremely effective H. pylori eradication regimen. The 3-day regimens tested both have poor cure rates. Pre-treatment with a proton pump inhibitor, higher doses or more frequent dosing may be necessary to increase the cure rate of short duration regimens. However, this could make them less acceptable than the H. pylori eradication regimens currently available.     

The impact of antibiotic resistance on the efficacy of three 7-day regimens against Helicobacter pylori

BACKGROUND: Antibiotic resistance affects the success of anti-Helicobacter pylori therapies and varies greatly from country to country. AIM: To compare the efficacy of three short-term triple regimens in relation to H. pylori primary resistance in our region. METHODS: We enrolled 210 H. pylori-positive dyspeptic patients for this randomized, open, parallel-group study. Three arms of 70 patients each received the following 1-week regimens: (1) ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (RCM); (2) bismuth subcitrate 240 mg b.d. + amoxycillin 1000 mg b.d. + metronidazole 500 mg b.d. (BAM); (3) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (OCM). H. pylori was assessed by CLO-test and histology before and 4 weeks after therapy. Antibiotic resistance was assessed by E-test. RESULTS: On intention-to-treat analysis RCM was more effective than OCM (84% vs. 69%; P < 0.03) and BAM (84% vs. 63%; P < 0.004). MIC determination was successful in 117 out of 210 patients (55%); metronidazole resistance was present in 52 out of 117 patients (44%) and clarithromycin resistance was present in 17 out of 117 patients (14%). Excellent cure rates were achieved when strains were sensitive to both antibiotics (100% with RCM and BAM and 90% with OCM), whereas RCM was superior to OCM (P=0.009) and BAM (P=0.001) with respect to overall resistant strains (94% vs. 57% and 38%, respectively). CONCLUSIONS: One-week RCM is the best regimen to eradicate H. pylori in our geographical area. This seems to be linked to the better ability of RCM compared to OCM and BAM in overcoming the high prevalence of H. pylori resistance to both metronidazole and clarithromycin in our region.     

One-week triple therapy with omeprazole, amoxycillin and either clarithromycin or metronidazole for cure of Helicobacter pylori infection

Aim: The present study was designed to evaluate the efficacy and tolerability of 1-week triple therapy regimens for Helicobacter pylori .
Methods: In two consecutive series, 120 patients with proven H. pylori infection and peptic ulcer disease or functional dyspepsia were treated with either omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (OAC; n=60) or with omeprazole 20 mg b.d., amoxycillin 1 g b.d. and metronidazole 400 mg b.d. over 1 week (OAM; n=60). H. pylori infection was assessed by rapid urease test, culture and histology before and 4 weeks after cessation of the eradication therapy.
Results: H. pylori eradication succeeded in 53 out of 60 patients by omeprazole–amoxycillin–clarithromycin (OAC) (88%; 95% CI 77–95%) and in 47 out of 60 patients by omeprazole–amoxycillin–metronidazole (OAM) (78%; 95% CI 66–88%) (P=0.22). Nine patients of each group available for follow-up reported adverse events (15.0 and 15.5%, respectively) without necessity of discontinuation of the study medications. Serious adverse events were not observed.
Conclusions: Simple and convenient 1-week triple therapies consisting of omeprazole, amoxycillin and either clarithromycin or metronidazole are sufficiently effective in eradicating H. pylori infection.     

One-week ranitidine bismuth citrate-based triple therapy for the eradication of Helicobacter pylori in Hong Kong with high prevalence of metronidazole resistance

AIM: To compare 1-week ranitidine bismuth citrate-based (RBC) triple therapy vs. omeprazole-based (O) triple therapy for the eradication of Helicobacter pylori infection in Hong Kong with high prevalence of metronidazole resistance. METHODS: Patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive either: (i) RBCCM: ranitidine bismuth citrate (pylorid) 400 mg, clarithromycin 250 mg and metronidazole 400 mg; or (ii) OCM: omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg, each given twice daily for 1 week. Endoscopy (CLO test, histology and culture) and 13C-urea breath test were performed before randomization and 6 weeks after drug treatment. RESULTS: A total of 180 patients were randomized. H. pylori eradication rates (intention-to-treat, n=180/per protocol, n=166) were 83%/92% for RBCCM and 66%/70% for OCM (P=0.01, intention-to-treat and P=0.001, per protocol, respectively). RBCCM treatment was unaffected by metronidazole susceptibility and achieved a significantly higher eradication rate in metronidazole-resistant cases (89%) than the OCM group (45%, P=0.0064). CONCLUSION: One-week ranitidine bismuth citrate-based triple therapy is significantly better than omeprazole-based triple therapy for the eradication of H. pylori infection, especially in metronidazole-resistant cases. It is an effective regimen for the eradication of H. pylori infection in regions with a high prevalence of metronidazole resistance.     

Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study

BACKGROUND: The efficacy of omeprazole-based eradication therapies has been determined mostly in populations with low to moderate prevalence of metronidazole resistant Helicobacter pylori, yet resistance is high in many regions. AIM AND METHODS: The H. pylori eradication and duodenal ulcer healing rates after 1 week of either omeprazole 40 mg mane, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM) or omeprazole 20 mg b.d., metronidazole 400 mg b. d. and clarithromycin 250 mg b.d. (OMC) were compared in a randomized trial in Australia and New Zealand. Patients had a further 1 week of omeprazole 20 mg. Outcome was assessed at 6 weeks with stringent criteria (endoscopy, biopsies and 13C-urea breath test). RESULTS: Of 220 subjects randomized, the H. pylori eradication rates (all patients treated/per protocol) were 82%/85% for OMC and 58%/63% for OAM (P= 0.001). Pre-treatment metronidazole resistance was present in 56% and clarithromycin resistance in 6%. The eradication rate for primary metronidazole resistance isolates treated with OMC was 80% (CI: 65-90%) compared with 45% (CI: 29-62%) for OAM, whereas for sensitive organisms, the eradication rates were 94% (CI: 79-99%) and 79% (CI: 62-91%), respectively. Duodenal ulcer healing was 96% for OMC and 87% for OAM. Compliance was excellent and both treatments were well-tolerated. CONCLUSIONS: OMC is a well-tolerated, effective therapy for H. pylori eradication and duodenal ulcer healing in this region despite the high metronidazole resistance rate. OAM is less effective, largely due to the impact of metronidazole resistance.     

The importance of clarithromycin dose in the management of Helicobacter pylori infection: a meta-analysis of triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole

BACKGROUND: It is not clear which dose of clarithromycin (500 mg b.d. or 250 mg b.d.) is more effective for Helicobacter pylori eradication in proton pump inhibitor-based triple therapies. METHODS: We undertook a meta-analysis of the effect of 7-day triple therapies consisting of a proton pump inhibitor (P), and clarithromycin (C) and amoxycillin (A) or metronidazole (M). A meta-analysis of all clinical trials performed in an adult population and published in English up to March 1998 was undertaken. Studies with doses of clarithromycin 500 mg b.d. or 250 mg b.d. only were included. RESULTS: A total of 82 studies (31 papers and 51 abstracts) involving 110 treatment arms and 6123 patients were analysed that met the predetermined inclusion and exclusion criteria. In the PAC combination, the pooled eradication rate in patients treated with clarithromycin 500 mg b.d. was 89.5% (95% CI: 86.9-92. 0%) by per protocol analysis and 86.6% (95% CI: 81.0-89.3%) by intention-to-treat analysis. These rates are significantly higher than those achieved with clarithromycin 250 mg b.d. (83.3% by per protocol and 78.2% by intention-to-treat analysis, both P < 0.0001). This difference was confirmed in head-to-head comparative studies. In the PMC regimen, clarithromycin 500 mg b.d. eradicated 90.8% (95% CI: 87.0-94.5%) of the infections compared to 88.5% (95% CI: 85.5-91. 5%) in patients treated with clarithromycin 250 mg b.d. by per protocol analysis (P = 0.082). The corresponding rates by intention-to-treat analysis for clarithromycin 500 mg b.d. and 250 mg b.d. was 88.3% and 86.7%, respectively (P = 0.259). CONCLUSIONS: Seven-day triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole are highly effective treatments for the eradication of H. pylori. Clarithromycin 500 mg b. d. should be used in these combinations to achieve the best first treatment results, which can minimize the subsequent development of bacterial resistance to clarithromycin and metronidazole.     

Effect of ornidazole and clarithromycin resistance on eradication of Helicobacter pylori in peptic ulcer disease

BACKGROUND: Clarithromycin and nitroimidazoles such as metronidazole and ornidazole are among the most frequently used antibiotics for curing Helicobacter pylori infection. However, controversial data exist on whether their in vitro resistance has a negative impact on treatment outcome. METHODS: Patients with H. pylori positive active peptic ulcer disease were randomly assigned to receive lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and ornidazole 500 mg b.d. (LAO) or lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) for 2 weeks. Pre-treatment resistance to ornidazole and clarithromycin was assessed by Epsilometer (E-) test. Four weeks after completion of treatment, patients underwent a 13C urea breath test to assess H. pylori status. RESULTS: Data from 80 patients with active peptic ulcer disease and positive H. pylori status were analysed. The prevalence of primary drug resistance was 25% for metronidazole and 7.5% for clarithromycin. In patients treated with LAO, effective treatment was achieved in 87% of metronidazole-susceptible, but only 30% of metronidazole-resistant strains (P < 0.01). In the LAC group, therapy was successful in 81% of clarithromycin-susceptible strains, whereas treatment failed in all patients with primary clarithromycin resistance (n = 3). CONCLUSION: Resistance against nitroimidazoles significantly affects treatment outcome in H. pylori eradication therapy.     

Triple therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer disease: results of a multicentre study in South-East Asia. South-East Asia Multicenter Study Group

BACKGROUND: The efficacy of proton pump inhibitor based triple therapy in patients from South-East Asia, where metronidazole resistance is reportedly high, has not been formally assessed in randomized, multicentre trials. AIM: To compare the eradication rates of Helicobacter pylori, ulcer healing rates and side-effects of three regimens of omeprazole triple therapy in patients with duodenal ulcer from South-East Asia and to study the impact of metronidazole resistance. METHODS: A single blind, randomized parallel group, comparative multicentre study. A total of 246 patients from 15 centres in four South-East Asian countries were randomized to receive OAC (omeprazole 20 mg b.d., amoxycillin 1 g b. d., clarithromycin 500 mg b.d.), OAM (omeprazole 20 mg b.d., amoxycillin 1 g b.d., metronidazole 400 mg b.d.) or OMC (omeprazole 20 mg b.d., metronidazole 400 mg b.d., clarithromycin 500 mg b.d.) for 7 days. After triple therapy, the patients were further randomized to receive either omeprazole or placebo for 7 days. Upper gastrointestinal endoscopy was performed before treatment and 4 weeks after treatment. Biopsies for culture and for histopathological examination for H. pylori were taken from corpus and antrum before treatment and 4 weeks after treatment. RESULTS: The eradication rates were intention-to-treat/per protocol (95% CI): OAC 87% (79-94%)/94% (89-100%); OAM 80% (70-89%)/91% (83-98%); OMC 85% (77-93%)/94% (88-100%). The difference in eradication rates between the three groups was not statistically significant (P=0.419). Pre-treatment metronidazole resistance, was found in 34% of isolates and was a significant prognostic factor in patients receiving OAM (odds ratio 5.26) but not in patients receiving OAC or OMC. CONCLUSIONS: All three treatment regimens were safe, well tolerated and highly effective for eradication of H. pylori and ulcer healing. Pre-treatment metronidazole resistance reduced the efficacy of OAM but did not affect the efficacy of OMC.     

Comparison of 1-week vs. 2- or 4-week therapy regimens with ranitidine bismuth citrate plus two antibiotics for Helicobacter pylori eradication

BACKGROUND: Helicobacter pylori eradication therapies based on ranitidine bismuth citrate have recently been introduced in clinical practice. AIM: To compare the efficacy of three regimens containing ranitidine bismuth citrate given for 1, 2 and 4 weeks, combined with two antibiotics for the first week, in the eradication of H. pylori. METHODS: Eighty-six consecutive patients (50 duodenal ulcer disease, 36 non-ulcer dyspepsia) with H. pylori infection were offered three eradication regimens: (a) 1-week group (n=28), ranitidine bismuth citrate 400 mg b.d. for 7 days; (b) 2-week group (n=29), ranitidine bismuth citrate 400 mg b.d. for 14 days; and (c) 4-week group (n=29), ranitidine bismuth citrate 400 mg b.d. for 28 days. In all patients, clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. were given for the first week. Endoscopy was repeated 1 month after the end of treatment and eradication was considered to be successful if both rapid urease test and histology were negative. RESULTS: Overall, H. pylori was eradicated in 84% (72/86) patients on intention-to-treat analysis, whereas the per protocol cure rate was 89% (72/81). Eradication rates were 23/27 (85%) (95% confidence interval (CI): 66-96%), 25/27 (92%) (95% CI: 76-99%) and 24/27 (89%) (95% CI: 71-98%) in the 1-, 2- and 4-week groups, respectively, on per protocol analysis, and 25/28 (82%) (95% CI: 63-94%), 25/29 (86%) (95% CI: 68-96%) and 24/29 (83%) (95% CI: 64-94%), respectively, on intention-to-treat analysis (P > 0.05, N.S.). No significant differences were observed between groups concerning duodenal ulcer healing, resolution of symptoms and adverse effects. CONCLUSIONS: The 1-week regimen with ranitidine bismuth citrate, clarithromycin and metronidazole is effective in H. pylori eradication. Prolongation of treatment with ranitidine bismuth citrate for 2 or 4 weeks does not achieve a statistically significant more favourable outcome.     

Eradication of Helicobacter pylori with pantoprazole and two antibiotics: a comparison of two short-term regimens

BACKGROUND: High rates of Helicobacter pylori eradication can be achieved by combining proton pump inhibitors with two antibiotics. However, in the search for an optimal therapy a direct comparison of different regimens is necessary. METHODS: For this open study, 331 patients with duodenal ulcer were screened and randomly allocated to either pantoprazole 40 mg b.d., clarithromycin 500 mg b.d., and metronidazole 500 mg b.d. (PCM) or pantoprazole 40 mg b.d., amoxycillin 1000 mg b.d., and clarithromycin 500 mg b.d. (PAC) for 7 days. Both combinations were followed by a 7-day therapy with pantoprazole 40 mg o.d. alone. Eradication of H. pylori was assessed by use of a 13C-urea breath test 4 weeks after the intake of the last medication. RESULTS: Eradication rates were 90% in intention-to-treat patients from the PCM (132 out of 147; 95% CI: 84-94%) and the PAC group (135 out of 150; 95% CI: 84-94%). H. pylori was eradicated in 112 out of 117 per protocol patients of the PCM group (96%; 95% CI: 90-99%) and in 119 out of 126 patients of the PAC group (94%; 95% CI: 89-98%). Rapid relief from ulcer pain and a decrease in the mean intensity of other gastrointestinal symptoms was observed. Sixty-nine patients reported adverse events, none of which were related to the intake of pantoprazole. Four serious adverse events, none related to the trial medication, were observed. CONCLUSIONS: Both pantoprazole-based short-term triple therapies are highly effective and well-tolerated treatment regimens in the eradication of H. pylori.     

Randomized controlled comparison of nitroimidazoles for the eradication of Helicobacter pylori and relief of ulcer-associated and non-ulcer dyspepsia

BACKGROUND: A combination of omeprazole, clarithromycin and either metronidazole or tinidazole is commonly used for Helicobacter pylori eradication. Metronidazole is considerably cheaper than tinidazole but the two have not previously been compared in a randomized trial. METHODS: One hundred and twenty dyspeptic H. pylori-positive patients with endoscopically defined peptic ulcer [DU (n = 65), GU (n = 12)] or non-ulcer dyspepsia (NUD, n = 43) were randomized to receive a 1-week course of twice daily omeprazole 20 mg, clarithromycin 250 mg and either metronidazole 400 mg (OCM) or tinidazole 500 mg (OCT) in a double-blind fashion. Eradication of H. pylori, safety and side-effects of treatment, dyspeptic symptom score and consumption of antisecretory drugs were assessed at 6 weeks and 1 year after treatment. RESULTS: H. pylori eradication was successfully achieved in 57/60 (95%, ITT analysis) of patients receiving OCT and 58/60 (97%, ITT analysis) receiving OCM. Both regimens had similar side-effect profiles, which accounted for only one patient withdrawal. All patients remained uninfected (as assessed by 14C-urea breath test) at 1-year follow-up, but major symptom improvements and decreased antisecretory drug use were only seen in patients with DU (P<0.0001). CONCLUSIONS: Treatment with OCM is as effective as the more expensive OCT at eradicating H. pylori. H. pylori eradication results in long-term relief of dyspeptic symptoms and reduced antisecretory consumption only in patients with DU, and not in those with NUD.     

Is a long‐term ranitidine‐based triple therapy against Helicobacter pylori only a heritage of the past? A prospective,randomized clinicopharmacological study

BACKGROUND: Acid suppression plus two antibiotics is currently considered the gold standard anti-Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. Aims: To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. METHODS: A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. RESULTS: On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02). CONCLUSION: Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens.     

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.     

Clarithromycin vs. furazolidone in quadruple therapy regimens for the treatment of Helicobacter pylori in a population with a high metronidazole resistance rate

BACKGROUND: The eradication of Helicobacter pylori plays a pivotal role in the treatment of peptic ulcer disease. Metronidazole resistance, common in Iran, is claimed to be a major reason for the failure of metronidazole-containing regimens. Both clarithromycin and furazolidone are potential alternatives for metronidazole. AIM: To assess and compare the effectiveness of clarithromycin- and furazolidone-based regimens in eradicating H. pylori in a population with a high metronidazole resistance rate. METHODS: Patients with proven duodenal ulcer and H. pylori infection were randomly assigned to one of two groups. The patients received 2 weeks of omeprazole 20 mg b.d., amoxicillin 1000 mg b.d, bismuth subcitrate 240 mg b.d. and either clarithromycin 500 mg b.d. (the OABC group) or furazolidone 200 mg b.d. (the OABF group). RESULTS: A total of 118 patients were randomized, 55 in the OABC group and 63 in the OABF group. The intention-to-treat eradication rate was 84% and 85% for the OABF and OABC groups, respectively. The per protocol eradication rates were 90% for both groups. CONCLUSIONS: OABC and OABF are both effective in eradicating H. pylori in areas where metronidazole resistance is a problem. OABF is a good alternative in the face of growing resistance to clarithromycin in developed countries, and is attractive for developing countries where clarithromycin is not readily available.     

Equally high efficacy of 4, 7 and 10-day triple therapies to eradicate Helicobacter pylori infection in patients with ulcer disease

BACKGROUND: In patients with ulcer disease the optimal dose and duration of Helicobacter pylori treatment containing omeprazole (O), metronidazole (M) and clarithromycin (C) has yet to be established. The efficacy might be influenced by metronidazole- and clarithromycin-resistance. AIM: To study the effect of duration of OMC treatment on its efficacy and influence of metronidazole-resistance and clarithromycin-resistance on the optimal duration. MATERIALS AND METHODS: Ulcer patients (n=76) were randomized to three double-blind treatments of 10 days: OMC 4 consisted of 4 days b.d. 20 mg omeprazole, 400 mg metronidazole and 250 mg clarithromycin switched over to 6 days b.d. 20 mg omeprazole and placebo antibiotics (n=27); OMC 7 consisted of 7 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg and 3 days b.d. omeprazole 20 mg and placebo antibiotics (n=25); OMC 10 consisted of 10 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (n=24). H. pylori was assessed by biopsies for culture and histology pre- and 4-6 weeks after OMC therapy. Metronidazole-resistance and clarithromycin-resistance were assessed by the E-test. RESULTS: Intention-to-treat-eradication rates were: OMC 4, 96%; OMC 7, 92%; and OMC 10, 96% (N.S.). All of the three per protocol eradication rates were 100% (95% CI: 85.2-100). Of 75 isolates, 16 were metronidazole-resistant and one was clarithromycin-resistant. CONCLUSION: In H. pylori-positive ulcer patients, OMC 4 is highly efficacious and as effective as OMC 7 and OMC 10. No influence of metronidazole-resistance or clarithromycin-resistance was observed.     

Furazolidone combination therapies for Helicobacter pylori infection in the United States

BACKGROUND: Antibiotic resistance has begun to impair the ability to cure Helicobacter pylori infection. AIM: To evaluate furazolidone as a component of combination therapies for treatment of H. pylori infection in the United States. METHODS: Patients with active H. pylori infection received furazolidone combination therapy for 14 days (furazolidone 100 mg and tetracycline 500 mg t.d.s.; omeprazole 20 mg o.d. in the morning and, depending on the pre-treatment antimicrobial susceptibility pattern, 500 mg of metronidazole or clarithromycin t.d.s.). RESULTS: A total of 27 patients received the metronidazole containing combination (cure rate 100%) and seven received the clarithromycin combination (cure rate 86%). Overall the cure rates for intention-to-treat was 97% (95% CI: 85% to 100%). The single failure took the clarithromycin containing combination for only 2 days (per protocol cure rate = 100%). Side-effects were common and led to discontinuation of therapy in 26% of patients. An attempt to eliminate metronidazole and clarithromycin and use furazolidone, tetracycline, and lansoprazole b.d. produced an unsatisfactory cure rate of 72%. CONCLUSION: Furazolidone combination therapy appears to be effective. Additional studies with different antimicrobial combinations and duration of therapy are warranted.     

Esomeprazole-based one-week triple therapy with clarithromycin and metronidazole is effective in eradicating Helicobacter pylori in the absence of antimicrobial resistance

AIM: This study aimed to investigate the effectiveness of a one-week triple therapy with esomeprazole, clarithromycin and metronidazole for eradication of Helicobacter pylori infection in the absence of antimicrobial resistance. METHODS: Patients testing positive for H. pylori susceptible to metronidazole and clarithromycin (E-test) were randomized to receive a one-week regimen with either esomeprazole 2 x 20 mg or omeprazole 2 x 20 mg in combination with clarithromycin 2 x 250 mg and metronidazole 2 x 400 mg. Follow-up endoscopy with histology and culture and/or rapid urease test was performed 4-8 weeks after the end of treatment. RESULTS: Eighty patients were randomized. Helicobacter pylori infection was cured in 38/39 patients of the esomeprazole group and 31/33 patients of the omeprazole group (per protocol 97.4% (95% confidence interval [CI], 86.2-99.9), 93.7% (95% CI, 79.2-99.2), P=0.59); intention-to-treat 90.4% (95% CI: 77.4-97.3), 81.6% (95% CI: 65.7-92.3), respectively. No major side effects occurred. Minor side effects occurred in eight (20%) and six (23%) patients during esomeprazole and omeprazole therapy, respectively. Post-treatment susceptibility testing revealed resistance to both metronidazole and clarithromycin in two of the three patients who failed. CONCLUSION: We conclude that esomeprazole, clarithromycin and metronidazole as one-week triple therapy is effective for eradication of H. pylori in the absence of antimicrobial resistance.     

Safety and efficacy of 7-day rabeprazole- and omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with documented peptic ulcer disease

AIM: A double-blind, randomized study was designed to determine whether rabeprazole- and omeprazole-based triple therapy regimens are therapeutically equivalent in the eradication of Helicobacter pylori. METHODS: Three hundred and forty-five patients with current or previously active peptic ulcer and a positive H. pylori urease test were randomly assigned to receive RCA, OCA, RCM or OCM twice daily for 7 days (R, rabeprazole 20 mg; O, omeprazole 20 mg; C, clarithromycin 500 mg; A, amoxicillin 1000 mg; M, metronidazole 400 mg). H. pylori eradication was documented by negative 13C-urea breath tests at 4 and 12 weeks, and was evaluated using a 2 x 2 factorial design with proton pump inhibitor and antibiotic as factors. RESULTS: Overall eradication rates (per protocol/intention-to-treat) were 87%/77% and 85%/75% with rabeprazole and omeprazole, respectively (not significant). However, a statistical interaction between proton pump inhibitor and antibiotic was identified. RCA produced a somewhat higher eradication rate than OCA (94% vs. 84%; difference, 9.8%; 95% confidence interval, - 0.7% to + 20.4%), whereas RCM produced a lower eradication rate than OCM (79% vs. 86%; difference, 8.1%; 95% confidence interval, - 21.4% to + 5.1%). Ulcer healing rates were > 90% with H. pylori eradication. Each regimen was well tolerated. CONCLUSIONS: Rabeprazole- and omeprazole-based triple therapy regimens are therapeutically equivalent in the eradication of H. pylori and well tolerated. The statistical interaction observed between the proton pump inhibitor and supplementary antibiotic may be due to chance.