Review article
Standard triple and sequential therapies for Helicobacter pylori eradication: An update

https://doi.org/10.1016/j.ejim.2012.07.006Get rights and content

Abstract

H. pylori infection remains a worldwide spread disease with a definite morbidity and mortality. Unfortunately, no current therapy regimen is able to cure the infection in all treated patients. The efficacy of the widely recommended triple therapies is decreasing, and a novel 10-day sequential therapy has been proposed. Data of 3 previous meta-analyses showed a significantly higher eradication rate following the sequential as compared to the 7–10 days triple therapies. The sequential therapy achieved significantly better results than triple therapies in children, elderly patients, non-ulcer dyspepsia patients, and in those infected with resistant strains towards either clarithromycin or metronidazole. We identified further 10 randomized trials. By pooling data, H. pylori infection was cured in 2,454 (86%; 95% CI: 84.7–87.3) out of 2,853 patients with the sequential therapy and in 2,320 (75.3%; 95% CI: 73.8–76.9) out of 3,079 patients treated with standard triple therapies (p < 0.001), corresponding to a number to treat (NNT) of 9. The comparison between the 10-day sequential regimen and 14-day triple therapies deserves further investigations.

Introduction

Despite H. pylori prevalence is declining in developed countries, such an infection remains a worldwide spread disease with a definite morbidity and mortality [1]. Indeed, this infection is the main cause of non-ulcer dyspepsia, peptic ulcers and gastric tumors, including both low-grade MALT-lymphoma and adenocarcinoma [2], [3], [4]. Moreover, an interaction between H. pylori and non-steroidal, anti-inflammatory drugs in damaging the gastroduodenal mucosa has been also recognized [5]. In addition, among extra-digestive diseases, reliable data shows an association between H. pylori infection and both idiopathic thrombocytopaenic purpura and idiopathic iron deficiency anaemia [6], [7]. The infection virtually persists for a long time if not opportunely cured, and no current therapy regimen is able to cure the infection in all treated patients [8]. Although different factors have been involved [9], therapy failure mainly depends on primary resistance towards different antibiotics – especially clarithromycin – which is increasing worldwide [10]. Moreover, vaccine is still in the experimental phase [11]. Therefore, nearly 30 years after H. pylori identification, its therapeutic management still remains an unsolved issue.

Section snippets

Triple therapies

The current standard triple therapies include a proton pump inhibitor (PPI), clarithromycin (500 mg) plus amoxicillin (1 g) or metronidazole/tinidazole (500 mg), all given twice daily for 7–14 days, as suggested in the International guidelines [12], [13]. Although 7-day triple therapies have been the most used treatment, the efficacy of these regimens has been constantly decreasing worldwide during the last decade. Based on these observations, current European guidelines confirmed the use of a

Sequential therapy

The sequential therapy was firstly introduced in Italy in 2000 [19]. This regimen is a 10-day therapy including a simple dual therapy with a PPI plus amoxicillin 1 g (both twice daily) given for the first 5 days followed by a triple therapy including a PPI, clarithromycin 500 mg, and tinidazole (all drugs given twice daily) for the remaining 5 days. Basically, the sequential regimen is a novel therapeutic approach based on different combinations of the available antibiotics. The first 5-day phase

Data of meta-analyses

Different trials compared the efficacy of sequential therapy with that of standard triple therapies in curing H. pylori infection. The first meta-analysis published on 2008 evaluated data of 10 randomized, controlled trials (RCTs), overall including 2,747 patients [40]. H. pylori eradication rates were 93.4% (95% CI: 91.3–95.5) in 1,363 patients following the sequential therapy and 76.9% (95% CI: 71–82.8) in 1,384 patients treated with the standard triple therapy. A following meta-analysis

Conclusions

Despite therapeutic management of H. pylori infection noticeably improved since its identification thirty years ago, no current therapy is able to achieve a 100% success rate. Indeed, a definite number of patients still remain infected despite three consecutive standard therapies [60]. The efficacy of triple therapies as first-line treatment is decreasing, and a longer 14-day regimen is now suggested in different guidelines [12], [37]. The 10-day sequential regimen has been pioneered more than

Learning points

  • •

    Despite therapeutic management of H. pylori infection noticeably improved since its identification thirty years ago, no current therapy is able to achieve a 100% success rate.

  • •

    The efficacy of triple therapies as first-line treatment is decreasing, whilst the 10-day sequential regimen has been proven to achieve higher cure rates.

  • •

    By pooling data, H. pylori infection was cured in 86% out of 2,853 patients treated with the sequential therapy and in 75.3% out of 3,079 patients treated with standard

Conflict of interest statement

None to declare.

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    Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.