Systematic review and meta-analysis: triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment

J Antimicrob Chemother. 2016 Oct;71(10):2740-53. doi: 10.1093/jac/dkw220. Epub 2016 Jun 23.


Background: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies.

Objectives: The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis.

Methods: Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates.

Results: Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies.

Conclusions: PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Amoxicillin / adverse effects
  • Amoxicillin / therapeutic use*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Ulcer Agents / therapeutic use
  • Drug Therapy, Combination
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects*
  • Humans
  • Metronidazole / adverse effects
  • Metronidazole / therapeutic use*
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*


  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Proton Pump Inhibitors
  • Metronidazole
  • Amoxicillin