Empiric Quadruple vs. Triple Therapy for Primary Treatment of Helicobacter pylori Infection: Systematic Review and Meta-Analysis of Efficacy and Tolerability

University of Michigan Medical Center, Ann Arbor, USA.
The American Journal of Gastroenterology (Impact Factor: 9.21). 09/2009; 105(1):65-73. DOI: 10.1038/ajg.2009.508
Source: PubMed

ABSTRACT Recent treatment guidelines recommend two first-line therapies for Helicobacter pylori infection: proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole (quadruple therapy) or PPI, clarithromycin, and amoxicillin (triple therapy). We performed a systematic review and meta-analysis to compare the efficacy and tolerability of these regimens as first-line treatment of H. pylori.
A search of MEDLINE, EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials, ACP Journal Club, the Database of Abstracts of Reviews of Effectiveness, Cochrane Methodology Register, Health Technology Assessment Database, and abstracts from prominent gastrointestinal scientific meetings was carried out. Randomized controlled trials (RCTs) comparing bismuth quadruple therapy to clarithromycin triple therapy were selected for meta-analysis. Two independent reviewers extracted data, using standardized data forms. Meta-analysis was carried out with the metan command in Stata 10.1. Funnel plots and subgroup analyses were carried out.
Nine RCTs (N=1,679) were included. Although dosing regimens of clarithromycin triple therapy were quite consistent between trials, dosing regimens varied considerably for bismuth quadruple therapy. Bismuth quadruple therapy achieved eradication in 78.3% of patients, whereas clarithromycin triple therapy achieved an eradication rate of 77.0% (risk ratio (RR)=1.002, 95% confidence interval (CI): 0.936-1.073). There was moderate heterogeneity and no evidence for significant publication bias. Subgroup analyses by study location, treatment duration, and study population did not account for the heterogeneity. There were no statistically significant differences in side effects yielded by quadruple vs. clarithromycin triple therapy (RR=1.04, 95% CI: 1.04-1.14).
Quadruple and triple therapies yielded similar eradication rates as primary therapy for H. pylori infection. Both therapies yielded suboptimal eradication rates. Patient compliance and side effects are similar for quadruple and triple therapies.

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    ABSTRACT: Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.
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    ABSTRACT: Objective Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori (HP) infection. The culture-guided triple therapy (chosen on the basis of a preliminary in-vitro susceptibility test) might help to increase treatment success in high antibiotic resistance regions. The aim of this study was to evaluate the effectiveness of treatment with clarithromycin in patients with clarithromycin-sensitive culture compared with patients treated empirically. Methods In this prospective and controlled trial, 111 naive HP-positive patients were randomized to receive standard triple therapy omeprazole (20 mg twice daily), amoxicillin (1 g twice daily), and clarithromycin (500 mg twice daily) for 10 days (OAC) after antimicrobial susceptibility testing if there was no resistance to clarithromycin (ClariS) or empirical 10-day OAC for first-line therapy of HP (ClariNA). Eradication was confirmed using the C-13-labelled urea breath test 6 weeks after therapy. Our primary outcome was HP eradication. Treatment adherence and adverse effects were recorded. Results The effectiveness of eradication by protocol with 10-day OAC therapy in the ClariS was 94% [95% confidence interval (CI): 0.83-0.98], which was 22% higher than ClariNA 72% (95% CI: 0.58-0.85; P=0.006). The odds ratio of eradication in ClariS was 1.30 (95% CI: 1.10-1.60; P<0.05 by logistic regression) and the number needed to treat was 5 (95% CI: 3-13). We found no significant difference in the occurrence of adverse effects or in compliance between the two groups. Conclusion The eradication rate was significantly higher with clarithromycin-based triple therapy for patients with clarithromycin-susceptible HP isolates compared with those for whom no information on the corresponding susceptibility was available ( number NCT01486082). (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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    ABSTRACT: In this review we elaborate on two main questions concerning the management of Helicobacter pylori infection in children. First, we focus on who should be treated. In the presence of Helicobacter pylori (H. pylori)-associated peptic ulcer disease, eradication of the micro-organism is recommended. When H. pylori infection is detected by biopsy-based methods in the absence of peptic ulcer disease in a child with dyspeptic symptoms, treatment of H. pylori infection may be considered. In infected children whose first degree relatives have gastric cancer, treatment can be offered. A 'test-and-treat' strategy is not and has never been recommended in children. The second issue to address is what the recommended treatments are. ESPGHAN/NASPGHAN recommends that treatment tailored to susceptibility testing should be the first choice in pediatric patients. The duration of therapy should be 10-14 days. Costs, compliance and adverse effects should be taken into account. Checking the result of eradication with a reliable non-invasive test such as the (13)C urea breath test, is recommended at least 4-8 weeks following completion of therapy.

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