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Aliment Pharmacol Ther. 2004 Nov 15;20(10):1071-82.

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

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School of Public Health, University of Texas, Dallas Regional Campus, Dallas, TX, USA.



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.


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


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.


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.


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

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