Eradicating Helicobacter pylori in Peptic Ulcer Disease Reduces Medical Costs in the Community

Background: Eradicating Helicobacter pylori markedly reduces ulcer recurrence in patients with peptic ulcer disease (PUD). Many decision analysis studies have concluded that eradicating H. pylori in PUD patients is more cost‐effective than maintaining antisecretory therapy. In 1995, we introduced an H. pylori eradication program into a large transportation company that experienced increased incidences of PUD among its employees along with increased medical costs, and we performed trend analysis of the actual medical costs of PUD in this cohort. Methods: In this cohort, there were approximately 8500 employees. H. pylori‐positive PUD patients were identified at the annual health check up. The patients received eradication therapy with lansoprazole, amoxicillin, and clarithromycin. After eradication, the patients were followed up by a yearly health check up. The annual number of patients who received eradication was recorded, and the annual direct medical costs of PUD therapy were analyzed. Results: A total of 440 H. pylori‐positive PUD patients received eradication therapy in a 7‐year period. Based on an intention‐to‐treat analysis, the eradication rate was 84.5% (372 of 440). The largest number of patients who received eradication therapy was found in 1995 (n = 115), and from 1995 to 2001 this number decreased yearly by 12.5 (95% confidence interval (CI): 5 to 20). Between 1989 and 1995, the annual medical costs arising of PUD therapy increased by ¥2.25 million (95% CI: 1.19 to 3.31) per year, being highest (¥22.75 million) in 1995. Between 1995 and 2001, the costs decreased by ¥3.88 million (95% CI: 3.16 to 4.59) per year. The cost in 2001 was 5.7% of the cost in 1995. The eradication program was terminated in 2001 because the prevalence of PUD diminished markedly, and the associated medical costs decreased as well. Conclusions: H. pylori eradication could reduce the number of PUD patients and associated medical costs in the workplace setting.     

Eradication of Helicobacter pylori infection reduces the incidence of peptic ulcer disease in patients using nonsteroidal anti-inflammatory drugs: a meta-analysis

Aim: To investigate the association between use of nonsteroidal anti‐inflammatory drugs (NSAID) and Helicobacter pylori infection, interactive effect of H. pylori infection and NSAID use on the development of peptic ulcer disease (PUD), and the effect of H. pylori eradication therapy on PUD development. Material and Methods: We performed a systematic literature search in EMBASE and PubMed for relevant articles published in English between January 1989 and August 2010, with the following MeSH and/or key words: non‐steroidal anti‐inflammatory drugs, or NSAIDs, Helicobacter pylori, or H. pylori, peptic ulcer disease or PUD, and randomized‐control study or clinical trial. The meta‐analysis was conducted using the Review Manager 4.2.2. Results: In the analysis of five studies, the pooled prevalence of H. pylori infection was 74.5% and 71.1% in NSAID users and non‐NSAID users, respectively, (OR = 0.65; 95% CI: 0.35–1.20, p = .170). In the analysis of nine studies, the pooled prevalence of PUD in NSAID users was 31.2% and 17.9% in the presence and absence of H. pylori infection, respectively, (OR = 3.08; 95% CI: 1.26–7.55, p = .010). Moreover, in the analysis of seven studies, PUD developed in 6.4% and 11.8% of NSAID users with and without eradication therapy, respectively (OR = 0.50; 95% CI: 0.36–0.74, p < .001). The preventive effect of the eradication therapy was further revealed in NSAID‐naive users (OR = 0.26; 95% CI: 0.14–0.49, p < .0001) and in the Asian population (OR = 0.30; 95% CI: 0.16–0.56, p < .001). Conclusion: NSAID use is not associated with H. pylori infection in patients with PUD. PUD is more common in H. pylori positive than in negative NSAID users. Moreover, H. pylori eradication therapy reduces PUD incidence in NSAID users, especially in naive users and in the Asian population.     

Rank order of success favors longer duration of imidazole-based therapy for Helicobacter pylori in duodenal ulcer disease: a randomized pilot study

Background. Studies on eradication therapy in developing countries have shown a success rate of 70–85%, which is suboptimal. Duration of therapy may be an important factor dictating eradication success in such regions. Aim. The study was undertaken to evaluate the effect of increasing the treatment period on eradication of Helicobacter pylori in duodenal ulcer disease. Methods. A randomized trial was carried out in which 64 consecutive H. pylori‐infected patients with duodenal ulcer disease were enrolled. The patients were randomized to one of the three trial arms. Therapy consisted of lansoprazole 30 mg twice a day (b.i.d.), amoxycillin 1 g b.i.d. and tinidazole 500 mg b.i.d. The treatment period was 1 week in group I, 2 weeks in group II and 3 weeks in group III. At inclusion, patients underwent endoscopy and the presence of H. pylori was documented by a positive urease test and C14 urea breath test. Four weeks after completion of eradication therapy, the patients were subjected to repeat endoscopy to assess ulcer healing and tests for H. pylori infection. Results. Sixty‐four patients (55 male and nine female; mean age 35.5 years) were enrolled in each group. The H. pylori eradication rate for group I (1 week of therapy) was 47.6%, that for group II (2 weeks of therapy) was 80%, and that for group III (3 weeks of therapy) was 91.3% (p = .003). The ulcer healing rates were 71.4, 80 and 95.6% in groups I, II and III, respectively (p = .09). Conclusion. The 3‐week regimen significantly improved the eradication rate as compared with the 1‐week regime. Increasing the duration of therapy significantly improved the chances of eradication of H. pylori in duodenal ulcer disease.     

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients

Objective. Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. Methods. This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori‐cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. Results. Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). Conclusions. Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.     

Is There a Benefit to Extending the Duration of Helicobacter pylori Sequential Therapy to 14 Days?

Background and Aims: Ten‐day sequential therapy with a proton‐pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori (H. pylori) eradication rates between 90 and 94% (i.e., Grade B success). It has been suggested that prolonging the duration of therapy might improve the treatment success. We tested whether prolonging treatment duration to 14‐days would improve the results to 95% or greater eradication. Methods: This was a multi‐center, single site, pilot study in which H. pylori‐infected patients received a 14‐day sequential therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, clarithromycin, and metronidazole for 7 days). H. pylori status was assessed 8 weeks after therapy. Success was defined as achieving 95% or greater eradication by per‐protocol (PP) analysis. Results: One hundred and twenty‐three subjects received the 14‐day sequential therapy. The eradication rate was 93.9% (95% confidence interval [CI], 89.5–98.3%) by PP and 91.9% (95% CI, 87.1–96.7%) by intention‐to‐treat analysis. Adverse events were experienced by 21.1%; compliance of 90% or greater was 95.9%. Conclusions: Extending sequential therapy to 14 days did not result in improving the treatment outcome to 95% or greater.     

Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days

Background: Ten‐day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori eradication rates of 90–94% (Grade B success). Aims: We tested whether prolonging treatment and continuing amoxicillin throughout the 14‐day treatment period would produce a ≥95% result. Methods: This was a multicenter pilot study in which H. pylori‐infected patients received a 14‐day sequential–concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H. pylori status was examined 8 weeks after therapy. Success was defined as achieving ≥95% eradication by per‐protocol analysis. Results: One hundred and seventeen subjects received hybrid therapy. The eradication rate was 99.1% (95% confidence interval (CI), 97.3–100.0%) by per‐protocol analysis and 97.4% by intention‐to‐treat analysis (95% CI, 94.5–100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%. Conclusions: Fourteen‐day hybrid sequential–concomitant therapy achieved >95%H. pylori eradication (Grade A result). Further studies are needed 1, in regions with different patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days.     

A modified bismuth-containing quadruple therapy including a short course of furazolidone for Helicobacter pylori eradication after sequential therapy failure

Background: Helicobacter pylori eradication has still remained a challenge, especially in case of failure to novel treatments. Therefore, we designed a study to evaluate the effects of a modified bismuth‐containing quadruple therapy including a short course of furazolidone on a group of patients whose sequential therapy had been unsuccessful. Materials and Methods: Thirty‐six H. pylori‐positive patients who had previously failed a clarithromycin‐containing sequential therapy enrolled the study. They received pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. Eight weeks after treatment, H. pylori eradication was reassessed using C14‐urea breath test. Results: Thirty five patients completed the study. H. pylori eradication rates were 80.6% (95% CI = 67.6–93.5) and 82.9% (95% CI = 70.6–95.2) according to intention‐to‐treat and per‐protocol analyses, respectively. All patients had excellent compliance to treatment, and no one interrupted therapy owing to adverse effects. Conclusion: Regarding the eradication rate (>80%), low price, and very low adverse effects, a 2‐week bismuth‐containing quadruple regimen including a short course of furazolidone can be an encouraging regimen for second‐line H. pylori eradication in case of sequential therapy failure. Possibly, it can be improved by alterations in dose, dosing intervals, and/or duration.     

Double-blind, Multicenter, Placebo-Controlled Evaluation Of Clarithromycin And Omeprazole For Helicobacter Pylori-Associated Duodenal Ulcer

Background. Eradication of Helicobacter pylori leads to faster ulcer healing and a significant decrease in ulcer recurrence. Clarithromycin is the most effective monotherapy for eradicating H. pylori from the gastric mucosa, and omeprazole frequently is used for the treatment of duodenal ulcer disease, prompting the interest to investigate rigorously the combination of clarithromycin and omeprazole for eradicating H. pylori. Materials and Methods. The aim of this double-blind, randomized, multicenter (n=30), multinational (n=10) study was to compare clarithromycin and omeprazole with omeprazole monotherapy for the eradication of H. pylori from the gastric mucosa, endoscopic healing, and reduction of symptoms and ulcer recurrence in patients with active duodenal ulcer. Patients with active duodenal ulcer associated with H. pylori infection were randomized to receive omeprazole, 40 mg every morning for 14 days, with either clarithromycin, 500 mg, or placebo three times daily, which was followed by omeprazole, 20 mg every morning for 14 days. Patients underwent endoscopy before enrolling in the study, immediately after finishing treatment, and at 4- to 6-week and 6-month follow-up evaluations or at the recurrence of symptoms. Results. Two hundred and eight patients with active duodenal ulcer associated with confirmed H. pylori infection were randomized to treatment with either clarithromycin and omeprazole (n=102) or omeprazole and placebo (n=106). Four to six weeks after treatment was completed, H. pylori was eradicated in 74% (95% confidence interval, 63.0%–82.4%) of patients receiving clarithromycin and omeprazole, compared with 1% (0.0%–6.2%) of patients receiving omeprazole monotherapy (p < .001). Clarithromycin resistance developed in eight patients treated with clarithromycin and omeprazole and in none given omeprazole and placebo. Ulcers, which were healed following treatment in more than 95% of study patients, recurred by the 6-month follow-up visit in 10% (5%–19%) of dual therapy recipients, compared with 50% (39%–61%) of those who took omeprazole alone (p <.001). Conclusion. Clarithromycin and omeprazole dual therapy is simple and well-tolerated and leads to consistently high eradication rates for patients with duodenal ulcer associated with H. pylori infection.     

Normalization of phospholipids concentration of the gastric mucosa was observed in patients with peptic ulcer after eradication of Helicobacter pylori

Background. Phospholipids concentration in the gastric mucosa decreased in patients with Helicobacter pylori infection. The aim of this study is to examine the effects of eradication of H. pylori on decreasing the phospholipids concentration in the gastric mucosa in patients with gastric or duodenal ulcer. Materials and Methods. Phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingonomyeline) were measured in biopsy specimens from the antrum and corpus using thin‐layer chromatography. In H. pylori positive patients with gastric ulcer (n = 26) and duodenal ulcer (n = 13), and H. pylori negative controls (n = 20), the biopsy specimens were obtained before and 3 months after eradication. Eradication was performed using lansoprazole, amoxycillin, and clarithromycin. Results. Compared with the H. pylori negative control group, the concentrations of phosphatidylcholine and phosphatidylethanolamine decreased significantly in the gastric ulcer group in both antrum and corpus mucosa, and in the duodenal ulcer group in antrum mucosa. This decrease returned to the control level after eradication. Conclusions. This study demonstrates that the eradication of H. pylori in patients with peptic ulcer normalized the decrease of phosphatidylcholine and phosphatidylethanolamine in the gastric mucosa.     

Interactions Among Gastric Somatostatin, Interleukin-8 and Mucosal Inflammation in Helicobacter pylori-Positive Peptic Ulcer Patients

Background. To investigate whether Helicobacter pylori infection, but not drugs, affects gastric somatostatin, interleukin‐8 (IL‐8), histological inflammation through eradication therapy, and interactions among these parameters. Methods. Twenty‐eight H. pylori‐positive patients (21 males; mean age 47.0 years) with either gastric ulcer (GU: n = 11) or duodenal ulcer (n = 17) diagnosed endoscopically were treated with dual therapy. Eradication was defined as negative microbiologic tests and ¹³C‐urea breath test. Levels of antral and gastric juice somatostatin and mucosal IL‐8 were measured by radioimmunoassay and enzyme‐linked immunosorbent assay, respectively. Histology was assessed by the Sydney system. Results. H. pylori was eradicated in 15 patients (10 males, 6 GU) out of 28 (54%). The patients’ backgrounds did not affect the eradication of H. pylori. Successes in eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL‐8 levels and histological gastritis. In contrast, persistent H. pylori infection did not affect somatostatin and histological gastritis. An inverse correlation was present between changes in somatostatin levels and histological activity. No relationship was observed in changed values between antral somatostatin and IL‐8. Conclusions. These results indicate that eradication of H. pylori, but not the drugs used, induced an increase in somatostatin levels in the antrum and gastric juice, suggesting a close relationship between H. pylori and gastric somatostatin regulation. A close correlation between an increase in gastric somatostatin levels and the normalization of histological activity was present, suggesting that certain peptide‐immune interactions in the gastric mucosa exist in H. pylori infection.     

Variables Influencing Outcome of Helicobacter pylori Eradication Therapy in South China

Background: Therapy combining a proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole is widely recommended for first‐line treatment for Helicobacter pylori infection. The purpose of this study was to examine the outcomes of PPI‐containing triple therapy and identify factors influencing the cure rate of H. pylori infection in South China. Materials and Methods: H. pylori positive patients with different occupations from 25 hospitals in five provinces of South China were enrolled. They received a PPI, metronidazole and amoxicillin triple therapy for a week. H. pylori eradication was evaluated by ¹³C‐urea breath test 4 weeks after therapy. Association between H. pylori eradication with occupation, gender, age, educational level, and protocol compliance was evaluated by Logistic regression. Results: Six hundred and seventy‐five were enrolled. The intention‐to‐treat and per‐protocol analyses showed overall cure rates of 60% (95% CI = 56.3–63.7%) and 64.5% (95% CI = 60.7–68.3%), respectively. Multivariate logistic regression showed that occupation, gender and protocol compliance were positively associated with the eradication rate (p < .01). The cure rate for those who took 80% or more of the prescribed drugs was 64.5% (95% CI = 60.7–68.3%) versus 14.6% (95% CI = 6–29%, p < .001) for those who took less. Lower eradication rates were also observed in farmers and women. Conclusions: The eradication rate with a PPI, metronidazole and amoxicillin triple therapy was unacceptably low in South China. These results suggest that studies of the eradication of H. pylori infection in China must take into account antibiotic resistance as well as patient occupation, gender, and protocol compliance. Gastric cancer and peptic ulcer disease are both important in China making methods to effectively and efficiently eradicate H. pylori a priority.     

Evaluation of a four-drug, three-antibiotic, nonbismuth-containing "concomitant" therapy as first-line Helicobacter pylori eradication regimen in Greece

Background: The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10‐day, four‐drug, three‐antibiotic, nonbismuth–containing concomitant regimen. Materials and Methods: This is a prospective, open‐label, multicenter study that included 131 patients infected with H. pylori. All patients were diagnosed with peptic ulcer disease or nonulcer dyspepsia by endoscopy. H. pylori infection was established by at least two positive tests among rapid urease test, gastric histology, and ¹³C‐urea breath test. For 10 days, all patients received esomeprazole 40 mg, amoxycillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all b.d. eradication was assessed with ¹³C urea breath test 8 weeks after the start of treatment. Intention‐to‐treat and per‐protocol eradication rates were determined. Results: One hundred and twenty‐seven of the 131 patients completed the study. At intention‐to‐treat analysis, the eradication rate was 91.6% (95% confidence interval (CI), 85.5–95.7%). For the per‐protocol analysis, the eradication rate was 94.5% (95% CI, 89–97.8%). Adverse events were noted in 42 of 131 (32.1%); drug compliance was excellent with 96.9% of the patients taking more than 90% of the prescribed medication. Conclusion: A 10‐day concomitant regimen appears to be an effective, safe, and well‐tolerated treatment option for first‐line H. pylori eradication in Greece.     

Increased primary resistance to recommended antibiotics negatively affects Helicobacter pylori eradication

Objective. To evaluate the efficacy of two commonly employed treatments for Helicobacter pylori infection and the impact of bacterial resistance to antibiotics on eradication rate. Methods. Ninety‐two consecutive H. pylori‐positive patients with active peptic ulcer disease were randomly enrolled to receive a 7‐day treatment with either lansoprazole 30 mg plus amoxicillin 1 g and clarithromycin 500 mg [all twice a day (b.i.d.), Group A, n = 46]; or bismuth subcitrate 125 mg four times a day (q.i.d.) plus tetracycline 500 mg q.i.d and furazolidone 200 mg b.i.d. (Group B, n = 46) H. pylori status was reassessed 30 days after completion of the therapy and bacterial resistance to the antibiotics was investigated using an in vitro assay. Results. Five patients from each study group were lost to follow up. Both treatments resulted in similar H. pylori eradication rate: 66–60% (per protocol), 59–52% (intention‐to‐treat) in Groups A and B, respectively (non significant). However, eradication improved to 79% in the absence of H. pylori resistance to clarithromycin or amoxicillin. Conclusion. Primary resistance to clarithromycin or amoxicillin may underscore a potentially serious problem for the eradication of H. pylori infection. Testing for bacterial resistance may become necessary to improve therapeutic efficacy.     

In Search of the Holy Grail of Heliocobacter pylori Remedies

In this issue, Gisbert et al. (pp. 157–62) present the results of a noncomparative study evaluating a twice daily, 5‐day regimen of ranitidine bismuth citrate, amoxicillin, clarithromycin and metronidazole twice daily for Helicobacter pylori cure. This study is one of a few stuides that evaluate a 5‐day triple antimicrobial regimen in combination with a antisecretory agent. Although the study design precludes making any definite conclusion, it does encourage additional investigation of these types of regimens. Randomized controlled trials (RCTs) using regimens containing multiple agents should consider both standard‐of‐care comparator regimens and comparator regimens that will provide a better understanding of why regimens are more effective or better tolerated. The goal of treatment should be to maintain a lower bound 95% confidence interval (CI) of the point estimate of greater than 80% and a ‘delta’ (lower bound 95% CI of the difference in rates) of less than 10%. All RCTs should conduct susceptibility testing to evaluate the impact of resistance on efficacy and explain eradication failures. Finally, consideration should be given to the inclusion of patients with functional dyspepsia in H. pylori studies evaluating H. pylori cure since patients with peptic ulcer disease are becoming harder to find.     

Moxifloxacin-containing triple therapy versus bismuth-containing quadruple therapy for second-line treatment of Helicobacter pylori infection: a meta-analysis

Background: Moxifloxacin‐containing triple therapy has been suggested as an alternative second‐line therapy for Helicobacter pylori infection. Aims: To systematically review the efficacy and tolerance of moxifloxacin‐containing triple therapy in second‐line H. pylori eradication, and to conduct a meta‐analysis of studies comparing this regimen with bismuth‐containing quadruple therapy. Materials and Methods: Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science, PubMed, Chinese Biomedical Literature Database (updated to December 2010), and manual searches were conducted. A meta‐analysis of all randomized controlled trials (RCTs) comparing moxifloxacin‐containing triple therapy to bismuth‐containing quadruple therapy in the second‐line treatment of H. pylori infection was performed. Results: Seven RCTs including 787 patients were assessed. The meta‐analysis showed that the eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (74.9 vs 61.4%, OR 1.89, 95% CI: 1.38–2.58, p < .0001); besides, the rates of side effects and discontinuing therapy because of side effects in the moxifloxacin group were significantly lower than those in the quadruple therapy group (side effects: 10.1 vs 27.8%, OR 0.27, 95% CI: 0.18–0.41, p < .00001; discontinuing therapy because of side effects: 1.4 vs 8.2%, OR 0.18, 95% CI: 0.08–0.40, p < .0001). These results were constant in the sensitivity analyses. Conclusion: Moxifloxacin‐containing triple regimen is more effective and better tolerated than the bismuth‐containing quadruple therapy in the second‐line treatment of H. pylori infection.     

Pilot studies to identify the optimum duration of concomitant Helicobacter pylori eradication therapy in Thailand

Background and Aim: Eradication rate for Helicobacter pylori infection with standard triple therapy has globally declined including in Thailand, and new regimens are required that provide reliable high eradication rates. The study was designed to determine whether concomitant therapy administered for either 5 or 10 days would produce a ≥ 95% (grade A) treatment success in H. pylori infected Thai subjects with nonulcer dyspepsia. Methods: Two prospective, but separate, pilot single‐center studies were carried out during September 2009–December 2010 at Thammasat University Hospital, Thailand. H. pylori infected subjects were randomized into the two pilot studies; either 5‐day or 10‐day concomitant therapy. Thai concomitant therapy consisted of rabeprazole (20 mg) twice daily, amoxicillin 1 g twice daily, metronidazole 400 mg three times a day, and clarithromycin MR 1 g once daily. H. pylori status was assessed by ¹³C‐urea breath test 4 weeks after completion of the treatment. Successful treatment was defined as achieving a grade A result (≥95%) and failure by <90% cured. Results: A total of 110 subjects were randomized (55 to the 5‐day treatment trial and 55 to the 10‐day regimen). Baseline subject demographic and clinical characteristics were similar in both studies. All subjects completed their assigned therapies. The 10‐day concomitant treatment trial was successful in 53 of the 55 subjects (96.4%; 95% CI 87.4–99.5%). The 5‐day concomitant pilot was judged to be a failure as only 49 of 55 subjects (89.1%; 95% CI = 77.7–95.8%) were cured. The frequency of adverse events was low and similar in the two studies. Conclusion: The 10‐day concomitant regimen provided excellent treatment success (eradication rate >95%) and was well tolerated. Ten‐day concomitant therapy is likely to become useful first‐line H. pylori eradication in Thailand.     

Effect of Helicobacter pylori infection on gastric acid secretion and meal-stimulated serum gastrin in children

Background. Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal‐stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods. Thirty‐six children aged 10–17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2–3 months after H. pylori eradication. Meal‐stimulated serum gastrin response was assessed before and 12 months after eradication. Results. H. pylori gastritis was typically antrum‐predominant. Acid secretion was greater in H. pylori‐positive patients with duodenal ulcer than in gastritis‐only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori‐positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre‐ and post‐H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal‐stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions. H. pylori infection in children is associated with a marked but reversible increase in meal‐stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.     

Eradication of Helicobacter pylori has no effect on gastric acidity in duodenal ulcer patients—evaluation of 24-h pH monitoring

It is accepted that eradication of Helicobacter pylori leads to healing of chronic active gastritis facilitates ulcer healing and prevents ulcer recurrence in duodenal ulcer (DU) patients. However, it is not entirely known whether the eradication of the bacteria normalizes gastric acid secretion and abolishes dyspeptic symptoms after ulcer healing. This study was aimed to evaluate the intragastric acidity and dyspeptic complaints before, and 3 months after, eradication in 18 endoscopically proven H. pylori positive DU patients. Gastric pH was measured by 24-h continuous intraluminal recording, serum gastrin measurements and Congo-red tests were also performed. Dyspeptic complaints and antacid consumptions were recorded in diary cards, antisecretory therapy was not allowed after the cessation of eradication therapy. Endoscopy, H. pylori status and Congo-red tests were controlled at the 6th and 12th week, while pH measurements and serum gastrin tests were performed at inclusion and 3 months later. Three patients dropped out and in 14 out of the remaining subjects healing of DUs and successful eradications were achieved by the 6th and 12th week controls. The 24-h median pH and the percentage of 24-h pH readings under pH 3 were not changing significantly by the 3-month controls (from 1.9±0.5 to 1.8±0.4 and from 52.6±5.5% to 58.6±5%, respectively). Similary, no significant changes were observed in serum gastrin levels and dyspeptic symptom scores (from 72±7 pg/ml to 56.7±8 pg/ml and from 2.69±0.4 to 1.26±0.3, respectively). The antacid consumption was almost stable when compared with the pre- and post-eradication periods. It was concluded that despite successful H. pylori eradication and healing of DU, intragastric acidity does not change significantly at least 3 months after the therapy. The persisting dyspeptic symptoms and the need for antacid consumption suggest that some healed ulcer patients require antisecretory therapy in the post-eradication period.     

Second-line Helicobacter pylori eradication: a randomized comparison of 1-week or 2-week bismuth-containing quadruple therapy

Objectives: The increasing levels of bacterial antibiotic resistance have increased the need to evaluate the second‐line treatments for Helicobacter pylori. Bismuth‐based quadruple therapy is recommended as a second‐line treatment, but the optimal duration of this treatment is still debatable. We prospectively analyzed the eradication rate of H. pylori according to the duration of the second‐line bismuth‐based quadruple therapy. Methods: One hundred and ninety‐nine patients who failed at H. pylori eradication were prospectively randomized to receive pantoprazole 40 mg twice daily, metronidazole 500 mg thrice daily, and bismuth subcitrate 300 mg and tetracycline 500 mg four times daily for 7 days (PBMT7) or for 14 days (PBMT14). The post‐treatment H. pylori status was determined by the ¹³C‐urea breath test. The eradication rates, drug compliance, and side effects of each group were evaluated. Results: The intention‐to‐treat (ITT) eradication rates were 81.6% (95% CI 73.9–89.3%, 80/98) in the PBMT7 arm and 85.1% (95% CI 78.2–92.0%, 86/101) in the PBMT14 arm (p = .028, noninferiority test), while the per‐protocol (PP) eradication rates were 89.6% (95% CI 83.2–96.0%, 78/87) and 96.2% (95% CI 92.0–100.0% 77/80) (p = .015, noninferiority test), respectively. The compliance was 88.8% (87/98) and 79.2% (80/101) in the PBMT7 and PBMT14 groups, respectively. (p = .066) The number of patients having severe side effects was 15.3% (15/98) and 21.8% (22/101) in the PBMT7 and PBMT14 groups, respectively, which was similar between both groups. (p = .243). Conclusions: Although PBMT7 was not inferior to PBMT14 statistically, PBMT could not demonstrate enough ITT/PP eradication rate. Therefore, it could be better to extend the duration of treatment for 2 weeks for the second‐line treatment of H. pylori in Korea.     

Sequential metronidazole-furazolidone or clarithromycin-furazolidone compared to clarithromycin-based quadruple regimens for the eradication of Helicobacter pylori in peptic ulcer disease: a double-blind randomized controlled trial

Background: Furazolidone is a much cheaper drug with a very low resistance against Helicobacter pylori compared to clarithromycin. We aim to evaluate safety and efficacy of a sequential furazolidone‐based regimen versus clarithromycin‐based therapy in H. pylori eradication for ulcer disease. Materials: Patients with proven peptic ulcer or duodenitis were randomized into three groups: OAB‐M‐F; metronidazole (M) (500 mg bid) for the first 5 days, followed by furazolidone (F) (200 mg bid) for the second 5 days; OAC‐P; clarithromycin (C) (500 mg bid) for 10 days; and OAB‐C‐F; clarithromycin (500 mg bid) for the first 5 days and furazolidone (200 mg bid) for the second 5 days. All groups received omeprazole (O) (20 mg bid) and amoxicillin (A) (1 g bid). Groups OAB‐M‐F and OAB‐C‐F were also given bismuth subcitrate (B) (240 mg bid), whereas a placebo (P) was given to group OAC‐P. Adverse events were scored and recorded. Two months after treatment, a C¹³‐urea breath test was performed. Results: Three hundred and ten patients were enrolled and 92 (OAB‐M‐F), 95 (OAC‐P), and 98 (OAB‐C‐F) completed the study. The intention‐to‐treat eradication rates were 78.5% (95% CI = 69–85), 81.1% (95% CI = 73–88), and 82% (95% CI = 74–89), and per‐protocol eradication rates were 91.3% (95% CI = 83–96), 90.4% (95% CI = 82–95), and 88.7% (95% CI = 81–94), for group OAB‐M‐F, OAC‐P, and OAB‐C‐F, respectively. Eradication rate differences did not reach statistical significance. The most common adverse event, bad taste, occurred in all groups, but more frequently in groups OAC‐P (34%) and OAB‐C‐F (32%), than OAB‐M‐F (14%) (p < .05). Adverse symptoms score were 0.88 ± 2.05 in group OAB‐M‐F, 1.15 ± 1.40 in group OAC‐P, and 1.87 ± 1.62 in group OAB‐C‐F. Conclusion: Furazolidone can replace clarithromycin in H. pylori eradication regimens because of lack of development of resistance and very low cost.