A Prospective, Randomized Study of Quadruple Therapy and High-Dose Dual Therapy for Treatment of Helicobacter Pylori Resistant to Both Metronidazole and Clarithromycin


Reprint requests to: Stephan Miehlke, M.D., Medical Department I, Technical University Hospital, Fetscherstr. 74, 01307 Dresden, Germany.


Background and Aim. Failure of primary anti-H. pylori therapy results in a high rate of antimicrobial resistance. Here, we investigated the efficacy of high-dose dual therapy and quadruple therapy as salvage treatments for eradication of H. pylori resistant to both metronidazole and clarithromycin.

Patients and Methods. Patients with at least one treatment failure and infected with H. pylori resistant to both metronidazole and clarithromycin, were randomized to receive either omeprazole 4 × 40 mg and amoxicillin 4 × 750 mg; or omeprazole 2 × 20 mg, bismuthcitrate 4 × 107 mg, metronidazole 4 × 500 mg and tetracycline 4 × 500 mg. Both regimens were given for 14 days. In cases of persistent infection, a cross-over therapy was performed.

Results. Eighty-four patients were randomized. Cure of H. pylori infection was achieved in 31 patients after dual therapy and in 35 patients after quadruple therapy (per protocol: 83.8% (95% CI, 67.9–93.8) and 92.1% (95% CI, 78.6–98.3), respectively (p = 0.71); intention to treat: 75.6% (95% CI: 59.7–87.6) and 81.4% (95% CI: 66.6–91.6), respectively (p = 0.60)). Cross-over therapy was performed in six of nine patients, four of whom were cured of the infection.

Conclusion. Both high-dose dual therapy and quadruple therapy are effective in curing H. pylori infection resistant to both metronidazole and clarithromycin in patients who experienced previous treatment failures.