Meta-analysis: the efficacy, adverse events, and adherence related to first-line anti-Helicobacter pylori quadruple therapies

Aliment Pharmacol Ther. 2004 Nov 15;20(10):1071-82. doi: 10.1111/j.1365-2036.2004.02248.x.


Background: Owing to rising drug-resistant Helicobacter pylori infections, currently recommended proton-pump inhibitor-based triple therapies are losing their efficacy, and regimens efficacious in the presence of drug resistance are needed.

Aims: To summarize the efficacy, safety and adherence of first-line quadruple H. pylori therapies in adults.

Methods: Meta-regression models identified factors explaining variation in the efficacy of first-line quadruple therapies from 145 treatment arms. Estimates of average efficacy were calculated within homogeneous groups.

Results: Quadruple therapy containing a gastric acid inhibitor, bismuth, metronidazole and tetracycline was enhanced when omeprazole was included, treatment duration lasted 10-14 days, and when therapy took place in the Netherlands, Hong Kong and Australia. Treatment efficacy decreased as the prevalence of metronidazole resistance increased. Even in areas with a high prevalence of metronidazole resistance, this quadruple regimen eradicated more than 85% of H. pylori infections when it contained omeprazole and was given for 10-14 days. Furthermore, in the presence of clarithromycin resistance, this quadruple regimen eradicated 90-100% of H. pylori infections, while the currently recommended triple therapy containing clarithromycin, amoxicillin and a proton-pump inhibitor eradicated only 25-61% (P < 0.001). Adherence and adverse events for quadruple therapy were similar to currently recommended triple therapies.

Conclusions: Guidelines should include quadruple therapy with a proton-pump inhibitor, a bismuth compound, metronidazole and tetracycline among recommended first-line anti-H. pylori therapies.

Publication types

  • Meta-Analysis

MeSH terms

  • Antacids / therapeutic use
  • Bismuth / therapeutic use
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination / therapeutic use*
  • Guideline Adherence
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Humans
  • Metronidazole / therapeutic use
  • Practice Guidelines as Topic
  • Tetracycline / therapeutic use
  • Treatment Outcome


  • Antacids
  • Metronidazole
  • Tetracycline
  • Bismuth