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[new one-week triple therapies with metronidazole for the eradication of Helicobacter pylori: clarithromycin or amoxycillin as the second antibiotic].

BACKGROUND: To compare the efficacy of two "new" one-week triple therapies (with omeprazole, metronidazole and clarithromycin or amoxycillin) for the eradication of Helicobacter pylori and healing duodenal ulcer. METHODS: Randomised therapeutic trial. Eighty-eight consecutive duodenal ulcer patients with H. pylori infection were studied. At endoscopy, biopsies from both gastric antrum and body were obtained for histologic study (H&E). Two different therapies were administered for one week: omeprazole (O) (20 mg b.i.d.) and metronidazole (M) (500 mg b.i.d.) associated with clarithromycin (C) (500 mg b.i.d.) (group OMC, n = 44) or amoxycillin (A) (1 g b.i.d.) (group OMA, n = 44). Endoscopy with biopsies was repeated one month after completing therapy, and a 13C-urea breath test was also performed. Compliance was evaluated by tablet count. Analysis of data: multiple logistic regression, intention-to-treat. Eradication was defined as the absence of H. pylori by all diagnostic methods. RESULTS: Mean age (standard deviation) was 45(14) years, 75% males. Distribution of variables was similar in both therapeutic groups. Forty-two patients in each group completed the protocol. Eradication was achieved in 90.5% (95% CI = 78-96%) in group OMC and in 57% (42-71%) in group OMA (p < 0.001). In the multivariate analysis the type of therapy was the only variable which influenced on H. pylori eradication (OR = 7.1; CI = 2.2-24; p = 0.001). Ulcer healing was demonstrated in 88% (75-95%) of patients in group OMC and in 71% (56-83%) in group OMA (p = 0.1). Ulcer healing was higher when eradication was achieved (90%; 80-95%) than in H. pylori-positive patients (50%; 31-69%) (p < 0.001). Eradication of H. pylori was the only variable which influenced on ulcer healing (OR = 9.3; CI = 2.8-31; p < 0.001). CONCLUSION: The "new" triple therapy with omeprazole, metronidazole and clarithromycin (administered in a twice-a-day basis and only for one week) had an excellent efficacy for the eradication of H. pylori, significantly higher than that obtained with amoxycillin instead of clarithromycin. Both therapies achieved a high ulcer healing rate when H. pylori was eradicated, even with omeprazole administered only for one week.

Adult↗

[Eradication of Helicobacter pylori in developing countries].

A NIH Consensus Conference recommended Helicobacter pylori eradication to all ulcer patients, based mainly on information coming from countries with a low prevalence of infection in general population. The epidemiological situation is different in developing countries, where a pandemic of H. pylori goes unchecked, and most people become infected at young age. It is possible that response to eradication therapies and reinfection rate were to be included among the differences between developed and developing countries, raising doubts about the worldwide applicability of NIH recommendations. Limited published evidence and our experience suggest that eradication therapies have a lower efficacy and reinfection rate is significantly higher in developing compared to developed countries. In spite of this, the risk of ulcer recurrence after H. pylori eradication is substantially reduced compared to antisecretory therapy. Model analysis to evaluate the cost-effectiveness of H. pylori eradication, using figures that probably include the clinical and costs situation of developing countries, suggests that also from an economic perspective H. pylori eradication should be the standard treatment for peptic ulcer disease in developing countries. Local studies must determine the best eradication therapy for a particular geographical location, and longer follow-up of eradicated patients is needed to determine the true reinfection rate.

Anti-Bacterial Agents↗

Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial.

CONTEXT: Although chronic Helicobacter pylori infection is associated with gastric cancer, the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown. OBJECTIVE: To determine whether treatment of H pylori infection reduces the incidence of gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized, placebo-controlled, population-based primary prevention study of 1630 healthy carriers of H pylori infection from Fujian Province, China, recruited in July 1994 and followed up until January 2002. A total of 988 participants did not have precancerous lesions (gastric atrophy, intestinal metaplasia, or gastric dysplasia) on study entry. INTERVENTION: Patients were randomly assigned to receive H pylori eradication treatment: a 2-week course of omeprazole, 20 mg, a combination product of amoxicillin and clavulanate potassium, 750 mg, and metronidazole, 400 mg, all twice daily (n = 817); or placebo (n = 813). MAIN OUTCOME MEASURES: The primary outcome measure was incidence of gastric cancer during follow-up, compared between H pylori eradication and placebo groups. The secondary outcome measure was incidence of gastric cancer in patients with or without precancerous lesions, compared between the 2 groups. RESULTS: Among the 18 new cases of gastric cancers that developed, no overall reduction was observed in participants who received H pylori eradication treatment (n = 7) compared with those who did not (n = 11) (P =.33). In a subgroup of patients with no precancerous lesions on presentation, no patient developed gastric cancer during a follow-up of 7.5 years after H pylori eradication treatment compared with those who received placebo (0 vs 6; P =.02). Smoking (hazard ratio [HR], 6.2; 95% confidence interval [CI], 2.3-16.5; P<.001) and older age (HR, 1.10; 95% CI, 1.05-1.15; P<.001) were independent risk factors for the development of gastric cancer in this cohort. CONCLUSIONS: We found that the incidence of gastric cancer development at the population level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period of 7.5 years in a high-risk region of China. In the subgroup of H pylori carriers without precancerous lesions, eradication of H pylori significantly decreased the development of gastric cancer. Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted.

Adult↗

Eradication of Helicobacter pylori for non-ulcer dyspepsia.

BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. These searches were updated in October 2004. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Seventeen randomised controlled trials were included in the systematic review. Fourteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Thirteen of these trials gave results as dichotomous outcomes evaluating 3186 patients and there was no significant heterogeneity between the studies. There was a 8% relative risk reduction in the H pylori eradication group (95% CI = 3% to 12%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 18 (95% CI = 12 to 48). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. AUTHORS' CONCLUSIONS: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Adult↗

Eradication of Helicobacter pylori for non-ulcer dyspepsia.

BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Twenty one randomised controlled trials were included in the systematic review. Eighteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Seventeen of these trials gave results as dichotomous outcomes evaluating 3566 patients and there was no significant heterogeneity between the studies. There was a 10% relative risk reduction in the H pylori eradication group (95% CI = 6% to 14%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 14 (95% CI = 10 to 25). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. AUTHORS' CONCLUSIONS: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Adult↗

Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis.

BACKGROUND: Lower respiratory tract infection with Pseudomonas aeruginosa (P. aeruginosa) occurs in most people with cystic fibrosis. Once chronic infection is established, P. aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate. OBJECTIVES: To determine whether antibiotic treatment of early P. aeruginosa infection in children and adults with cystic fibrosis eradicates the organism and improves clinical and microbiological outcome. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of most recent search: May 2004 SELECTION CRITERIA: We included randomised controlled trials of people with cystic fibrosis, in whom P. aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo or usual treatment (or both) or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls. DATA COLLECTION AND ANALYSIS: Both authors independently assessed selected trials, assessed methodological quality and extracted data. MAIN RESULTS: The search identified 15 trials. Three trials (69 participants) were eligible for inclusion. There is evidence from two randomised controlled trials, of questionable methodological quality, that treatment of early P. aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo and that this effect may persist for up to 12 months, however incomplete data from one of the trials precludes an accurate analysis. One randomised controlled trial of oral ciprofloxacin and nebulised colisitin versus usual treatment was identified. This trial was of poor methodological quality. The results suggested treatment of early infection results in microbiological eradication of P. aeruginosa more often than usual treatment, after two years, RR 0.24 (95% CI 0.06 to 0.96). There is insufficient evidence to determine whether antibiotic strategies for the eradication of early P. aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. AUTHORS' CONCLUSIONS: From the three trials included in this review, there is some evidence that antibiotic treatment of early P. aeruginosa results in short-term eradication but it remains uncertain whether there is clinical benefit to people with cystic fibrosis.

Anti-Bacterial Agents↗

Eradication of Helicobacter pylori and long-term outcome of functional dyspepsia. A clinical endoscopic study.

The aim of this study was to assess the effect of colloidal bismuth subcitrate (CBS) and metronidazole on Helicobacter pylori eradication and on the course of symptoms due to functional dyspepsia. Forty-one patients with functional dyspepsia were entered into the study and randomized to treatment with CBS (120 mg four times a day) for four weeks combined with metronidazole (250 mg four times a day) for one week (group A, N = 21) or matching placebo (group B, N = 20). The severity of gastritis and of bacterial colonization and the symptom score was assessed by endoscopy and clinical evaluation at baseline and after four, eight, and 24 weeks from the start of the treatment. With intent-to-treat analysis eradication was achieved in 16/25 (64%) patients in group A and in 6/24 (25%) in group B. At eight and 24 weeks the gastritis score was significantly lower only in those patients with eradication. No change was seen in patients in whom the bacteria was not eradicated. The symptom score at eight weeks was considerably lower both in patients with eradication and in those with infection. However, at 24 weeks a gradual decrease in the symptom score in patients with eradication and a worsening of symptoms in controls was observed. No differences were observed between patients with ulcerlike and those with dysmotility-like dyspepsia. The study confirms the need for a long observation period after antibacterial treatment in patients with functional dyspepsia and suggests that Helicobacter pylori-eradicating treatment improves the course of this functional syndrome.

Adolescent↗

Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients.

OBJECTIVE: Eradication of Helicobacter pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. The principal enzyme involved in PPIs metabolism is CYP2C19, which exhibits an interindividual variability of activity, mainly due to genetic polymorphism. Two alleles (CYP2C19*2 and CYP2C19*3), responsible for slow PPIs metabolism, were previously associated with higher efficacy of eradication. Recently, a novel CYP2C19 gene variant (CYP2C19*17), associated with faster metabolism of CYP2C19 substrates, was described. In the present study, a potential association between CYP2C19*17 allele and lower H. pylori eradication efficacy was tested in a group of peptic ulcer patients. METHODS: A total of 125 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole+amoxicillin+metronidazole). Subsequently, the patients were divided into two groups (group 1 - success, and group 2 - failure of eradication after therapy) and genotyped for the presence of CYP2C19 variant alleles (*2, *3, and *17). RESULTS: Frequency of CYP2C19 alleles in two groups of patients were: 56.4 versus 65 (p=0.060) for *1, 15.4 versus 5.3 (p=0.015) for *2, and 28.2 versus 25.5 (p=0.663) for *17 allele, respectively. CYP2C19*3 was not detected in the evaluated population. No significant differences in frequency nor distribution of *17 allele were found between two groups of patients. CYP2C19*2 allele was associated with successful H. pylori eradication (p<0.02), *2 allele carriers were found to be over 4-times more prone to the treatment compared to *1/*1 homozygotes (OR=4.2, p=0.015). CONCLUSION: Our results suggest that, contrary to CYP2C19*2, CYP2C19*17 allele has no impact on efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Results of triple eradication therapy in Japanese children: a retrospective multicenter study.

BACKGROUND: Large-scale clinical trials in children are lacking concerning Helicobacter pylori eradication therapies. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapies in Japanese children. METHODS: This was a retrospective analysis of the first- and second-line PPI-based triple therapies from pediatric gastrointestinal units between 1996 and 2003. Data collected included doses and duration of regimens, drug compliance, success or failure of eradication, ulcer healing, and symptom response of those with dyspepsia and no ulcers. The results of antibiotic susceptibility tests were also reported in cases where these were performed. RESULTS: A total of 149 pediatric patients (mean age, 12.6 years) were studied, including 123 patients who received first-line therapy: 115 received a PPI plus amoxicillin and clarithromycin (PAC) and 8 received a PPI plus amoxicillin and metronidazole (PAM). Overall eradication rates of the first-line PAC and PAM therapies were 77.4% and 87.5%, respectively ( P = 0.68). All 14 patients with failed PAC therapy received the second-line PAM regimen, resulting in an eradication rate of 100%. Mild side effects were reported only in PAC regimens (13.8%). Primary resistance to amoxicillin, clarithromycin, and metronidazole was detected in 0%, 34.7%, and 12.5% of the strains, respectively. The PAC regimen showed a high eradication rate for clarithromycin-susceptible strains (91.7%), but was relatively ineffective for resistant strains (40.0%) ( P < 0.01). Eradication of H. pylori was associated with ulcer healing and symptomatic improvement among those with gastritis only (both; P < 0.001). Among 17 patients with iron-deficiency anemia, post-treatment hemoglobin levels were higher than the pretreatment levels ( P < 0.001). CONCLUSIONS: The PAC regimen is effective in children. Clarithromycin resistance is associated with eradication failure. Metronidazole is a good substitute for clarithromycin as the second-line option for children.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Immunological and molecular analysis of B lymphocytes in low-grade MALT lymphoma of the stomach. Are there any useful markers for predicting outcome after Helicobacter pylori eradication?

BACKGROUND: Although Helicobacter pylori eradication is effective in treating low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the condition in some patients deteriorates even after the eradication. Therefore, it is important to predict the disease outcome before starting H. pylori eradication. We investigated the usefulness of flow cytometry, quantifying CD19- and CD20-positive B lymphocytes in MALT lymphoma tissue, for predicting the disease outcome after H. pylori eradication. METHODS: Tissue specimens from 14 patients with H. pylori-positive low-grade gastric MALT lymphoma were examined by histology, Southern blotting, and flow cytometry before therapy. Serum levels of soluble interleukin (IL)-2 receptor were also measured. The relationship between the data and the prognosis after H. pylori eradication was analyzed. RESULTS: Remission occurred in 10 of the 14 patients. The condition in the 4 remaining patients deteriorated even after H. pylori eradication. The percentages of CD19- and CD20-positive cells in MALT lymphoma tissue from the patients in remission were both significantly lower than those in the tissue from patients not in remission. Indeed, 4 of the 5 patients in whom both CD19- and CD20-positive cells accounted for more than 50% of the total number of lymphocytes had gastrectomy, whereas all patients in whom both CD19- and CD20-positive cells accounted for less than 50% of the total number of lymphocytes achieved remission. Although immunoglobulin gene rearrangement was present in all patients operated on, there were also 6 patients whose MALT lymphoma was ameliorated in spite of the presence of gene rearrangement. The serum level of soluble IL-2 receptor was in the normal range in all patients tested. CONCLUSIONS: Analysis of mature B-cell markers in MALT lymphoma tissue is more useful than the examination of immunoglobulin gene rearrangement or serum levels of soluble IL-2 receptor in predicting the outcome of low-grade gastric MALT lymphoma after H. pylori eradication.

Antigens, CD19↗

Helicobacter pylori eradication therapy for the remnant stomach after gastrectomy.

BACKGROUND: The remnant stomach after surgery for gastric cancer is at high risk for the metachronous development of multiple gastric cancers. Here, we report on eradication therapy of Helicobacter pylori in the remnant stomach, comparing the eradication rate with that in unoperated stomachs. We examined gross and histological changes after treatment. METHODS: Forty H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based dual and triple therapies. After eradication, histological changes were classified on the basis of the updated Sydney system. RESULTS: The eradication rate in the remnant stomach was 70% (14 of 20) after dual therapy and 90% (18 of 20) after triple therapy, using per-protocol analysis, and these rates were comparable to the rates of 70% (186 of 264) and 88% (58 of 66), respectively, in nonsurgery patients. After eradication, three sites in the remnant stomach showed similar histological changes: significant decreases in inflammation and activity scores (P < 0.001) and no significant changes in glandular atrophy and intestinal metaplasia scores. CONCLUSION: PPI-based therapy was as effective for H. pylori eradication in the remnant stomach as in the unoperated stomach, and eradication therapy resulted in a significant decrease in inflammatory cell infiltration of the mucosal layer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Eradication of Helicobacter pylori in clinical situations.

Helicobacter pylori is prevalent worldwide, especially in developing countries, and is associated with several upper gastrointestinal diseases. Since it is present in over 90% of duodenal ulcer patients, empirical eradication in these patients is often recommended. In gastric ulcer patients, eradication is indicated only after the infection is confirmed. Testing for H. pylori infection should be carried out in patients with peptic ulcer hemorrhage, because eradication has been shown to reduce recurrent bleeding. Both H. pylori and NSAIDs are risk factors for peptic ulceration, and it is reasonable to screen for and eradicate H. pylori infection in peptic ulcer patients taking NSAIDs. H. pylori is a group I carcinogen for gastric adenocarcinoma, and should be eradicated for the primary prevention of this cancer. Eradication of this organism has been reported to result in regression of early low-grade mucosa-associated lymphoid tissue lymphoma. The role of H. pylori infection in the causation of gastroesophageal reflux and non-ulcer dyspepsia is not clearly established. Several tests are available for the diagnosis of H. pylori infection. These include invasive tests, such as histology, culture and urease test, and non-invasive tests, such as serology, urea breath test and stool antigen test. The choice of test is determined by clinical indication, pretest probability of infection, as well as the availability, cost, sensitivity and specificity of the test. H. pylori eradication therapy using proton pump inhibitor with clarithromycin and amoxycillin for 7 days has a success rate of 85-90%. Improved living standard and sanitation are vital in the control of H. pylori transmission and infection. Future development may include the use of vaccines against H. pylori, and therapies specifically targeting cagA strains of the bacteria.

Anti-Inflammatory Agents, Non-Steroidal↗

13C-urea breath test for success of Helicobacter pylori eradication: study of 5885 Israeli patients.

Helicobacter pylori (Hp) infection is highly prevalent in many countries and may cause gastritis, peptic ulcer disease, gastric cancer, and lymphoma. Successful eradication depends on the specific treatment used, patient compliance, and Hp antibiotic resistance. The primary aim was to characterize groups of patients with one or more failures of Hp eradication treatment. The secondary aim was to evaluate the factors that influence eradication failure. Between April 1, 1998, and December 31, 2001, 5885 patients were studied for the success of Hp eradication with the 13C-urea breath test (13C-UBT): 5442 after one course of treatment (Group I), 380 after two courses (Group II), and 63 after three courses (Group III). The 13C-UBT was positive in 27.8%, 37.4%, and 47.6% of patients in Groups I, II, and III, respectively (P(I-II) = 0.000, P(II-III) = 0.126). A combination of omeprazole, amoxicillin, and clarithromycin (OAC) was used in 31.3%, 27.4%, and 7.9% of Groups I, II, and III, respectively, and a combination of omeprazole, amoxicillin, and metronidazole (OAM) in 15.2%, 28.9%, and 28.6%, respectively. Regimens that contained clarithromycin were used in decreasing order in Groups I, II, and III, and regimens containing metronidazole, bismuth, or tetracycline, in increasing order. The only good prognostic factor for successful eradication was Israeli origin, while European-American and Asian-African origin, recurrence of symptoms, a history of duodenal ulcer, and chronic proton pump inhibitor (PPI) use did not favor successful eradication. Our results suggest that origin, history of peptic disease, and chronic PPI use are predictors of eradication failure.

Adolescent↗

A follow-up study on the effect of Helicobacter pylori eradication on the severity of gastric histology.

Helicobacter pylori genetic diversity and geographic distribution affect the severity of gastric histology; while eradication heals gastritis, the improvement of atrophy and intestinal metaplasia (IM) is still controversial. We investigated whether H. pylori infection and genotypes (cagA-vacA) influence the histological changes and whether eradication resolves these changes. Twenty-one patients (11 duodenal ulcer, 2 gastric ulcer, 8 gastritis) received treatment. Biopsies for CLO, PCR, histology, and culture were collected before and at 1 and 12 months after treatment, and serum samples at 0, 1, 2, 6, and 12 months. H. pylori eradication was achieved in 71% of the patients. Histological scores for H. pylori densities were significantly higher in the antrum and incisura angularis. Scores for mononuclear cell and neutrophil infiltration were significantly higher in regions with a high H. pylori density and improved progressively after eradication. Eight patients with atrophy including five with IM showed no significant changes 12 months after eradication. The cagA gene, detected in 13 (62%), the vacA-sla gene, in 20 (95%), and the vacA-m1 gene, in 12 (57%) of 21 patients were significantly associated with duodenal ulcer. A gradual decline in antibody titer reached an average of 67% 12 months after eradication. H. pylori infection and the associated genotypes (cagA of Western type) affect the severity of the gastric histology (mild forms of atrophy and IM) and the disease outcome. Eradication of H. pylori resulted in healing of gastritis, but with no significant improvement in atrophy or IM.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Factors associated with the development of reflux esophagitis after Helicobacter pylori eradication.

We investigated whether Helicobacter pylori (HP) eradication increases the incidence of reflux esophagitis (RE) in patients with peptic ulcers. From 2001-2005 consecutive out patients with peptic ulcers and HP received eradication and were followed endoscopically. HP was cured in 119 and RE developed in 33 of the 153 patients. RE developed in 24 of the 119 HP-eradicated patients and 9 of the 34 HP-persistent patients. The estimated RE occurrence rate within 1 year was higher in the HP-eradicated patients than in the HP-persistent patients, but it was reversed at 2 years by the Kaplan-Meier analysis. In 76 patients follow up for > or = 18 months, hiatal hernia, duodenal ulcer, and eradication failure were significantly associated with the increased RE rate by univariate and multivariate analysis. The follow-up period after HP eradication affected the RE occurrence rate, and eradication failure significantly increased the RE development in patients followed up for > or = 18 months.

Adult↗

Smoking increases the treatment failure for Helicobacter pylori eradication.

PURPOSE: Treatment failure for Helicobacter pylori (H. pylori) eradication is encountered in approximately 10-20% of patients, and many studies have pointed to a link with smoking. To investigate the effects of smoking on eradication outcome, we performed a meta-analysis. METHODS: A PubMed search was performed to retrieve articles published up to August 2005. Pooled odds ratio (OR) and differences rate for H. pylori eradication failure in smokers compared with nonsmokers were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: Twenty-two published studies (5538 patients), which provided information on eradication failure according to smoking status, were included in the analysis. The summary OR for eradication failure among smokers relative to nonsmokers was 1.95 (95% confidence interval [CI]: 1.55-2.45; P <.01). It corresponds with the differences in eradication rates between smokers and nonsmokers (8.4% [95% CI: 3.3-13.5%, P <.01]). Meta-regression analysis demonstrated that a high proportion of nonulcer dyspepsia patients in studies revealed a higher failure rate among smokers, compared with a low proportion of nonulcer dyspepsia. CONCLUSIONS: Our meta-analysis demonstrated that smoking increases the treatment failure rate for H. pylori eradication.

Anti-Bacterial Agents↗

CYP2C19 polymorphism is a major predictor of treatment failure in white patients by use of lansoprazole-based quadruple therapy for eradication of Helicobacter pylori.

OBJECTIVE: Proton pump inhibitors, metabolized by the polymorphic enzyme cytochrome P450 (CYP) 2C19, are essential drugs for Helicobacter pylori eradication. It was reported that patients with CYP2C19 wild type in Asia had lower eradication rates. This study tests the hypothesis that CYP2C19 wild type ( wt/wt ) in white patients is also associated with a higher probability of treatment failure. METHODS: This was a cohort study involving 131 H pylori -positive white (German) patients treated by quadruple therapy including lansoprazole (30 mg twice daily for 5 days). Eradication success, as well as lansoprazole trough steady-state serum concentrations, was determined according to different CYP2C19 genotypes. RESULTS: We found 3 homozygous variant patients (2.3%) ( mt/mt, CYP2C19*2/*2 ), 42 heterozygous patients (32.1%) ( wt/mt, CYP2C19*1/*2 ), and 86 wild-type individuals (65.6%). Significant differences in eradication success could be found between wt/wt patients (80.2%) versus combined mt/mt (100%) and wt/mt patients (97.8%) ( P <.01; odds ratio, 10.8 [confidence interval, 1.4-84]), which were associated with corresponding changes in the serum levels of lansoprazole (median, 753 ng/mL for mt/mt, 59 ng/mL for wt/mt, and 21 ng/mL for wt/wt; P <.001). Apart from antibiotic resistance, CYP2C19 polymorphism was the most important influencing factor for eradication success on multivariate analysis ( P <.0001). CONCLUSION: Eradication rates of H pylori highly depend on CYP2C19 in white patients if standard doses of lansoprazole (30 mg twice daily) are administered within a quadruple regimen. Because wt/wt individuals have lower eradication rates and lower serum concentrations of lansoprazole, these patients might benefit from a higher proton pump inhibitor dosage.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Influences of proinflammatory and anti-inflammatory cytokine polymorphisms on eradication rates of clarithromycin-sensitive strains of Helicobacter pylori by triple therapy.

BACKGROUNDS AND AIMS: Polymorphisms of proinflammatory cytokines, such as interleukin (IL) 1beta and tumor necrosis factor (TNF) alpha, are associated with individual differences in gastric mucosal inflammation and acid inhibition in response to Helicobacter pylori infection. We investigated whether inflammation-related cytokine polymorphisms would influence the eradication rates of H pylori by a triple-therapy regimen. METHODS: Three hundred sixty patients infected with clarithromycin-sensitive strains of H pylori were genotyped for IL1B -511, IL1RN, TNFA -857/-863/-1,031, IL10 -1,082/-819/-592, and CYP2C19 and underwent triple therapy for 1 week with a proton pump inhibitor (20 mg omeprazole, 30 mg lansoprazole, or 10 mg rabeprazole) twice daily, 400 mg clarithromycin twice daily, and 750 mg amoxicillin (INN, amoxicilline) twice daily. The influences of the previously mentioned polymorphisms on the eradication rates were analyzed. RESULTS: The intention-to-treat-based total eradication rate was 83.6% (301/360). The logistic regression analysis revealed that polymorphisms of CYP2C19 and IL1B -511 were independently associated with the eradication rates, but other cytokine polymorphisms were not associated with these rates. The eradication rates in patients with IL1B -511 C/C, C/T, and T/T genotypes were 72.2% (70/97), 87.7% (164/187), and 88.2% (67/76), respectively (P = .0017). When patients were stratified by CYP2C19 genotype status, IL1B -511 genotype-dependent differences in eradication rates were observed in homozygous extensive metabolizers (EMs) but not in heterozygous EMs and poor metabolizers of CYP2C19. The eradication rate in homozygous EM patients with the IL1B -511 C/C genotype was quite low (51.1% [22/43]). CONCLUSIONS: IL1B -511 polymorphism, but not IL1RN, TNFA, or IL10 polymorphism, is one of the determinants of triple therapy for clarithromycin-sensitive strains of H pylori in CYP2C19 homozygous EMs.

Anti-Bacterial Agents↗