Background: While addition of metronidazole to the omeprazole-amoxycillin combination has been shown to be advantageous, the optimal dosage and drug distribution of the antimicrobials has not been sufficiently evaluated.
Aim: To investigate the efficacy of two different regimens of omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection.
Methods: Two hundred and fifty-five patients with H. pylori associated duodenal ulcers were randomly treated with either a 1-week regimen of omeprazole 20 mg b.d., amoxycillin 1000 mg b.d. and metronidazole 800 mg b.d. (OAM b.d.) or a combination of omeprazole 40 mg o.d., amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM t.d.s.). All patients subsequently received omeprazole 20 mg o.d. for an additional 3 weeks. H. pylori status was assessed by histology and 13C-UBT prior to treatment and 8 weeks after randomization. Additional biopsies were obtained for H. pylori culture to determine primary and secondary resistance to metronidazole by agar dilution.
Results: Two hundred and thirty-seven patients were included in the intention-to-treat analysis and 198 patients in the per protocol analysis. With intention-to-treat analysis, the cure rate was 77% after treatment with OAM b.d. (95% CI, 69%-85%) and 76% after OAM t. d.s. therapy (95% CI, 67%-83%). Ulcer healing (intention-to-treat analysis) was documented in 95% of patients in the OAM b.d. group (n=122) and in 97% of patients in the OAM t.d.s. group (n=115). Adverse events were reported in 26 (20%) and in 18 (14%) patients in the OAM b.d. and OAM t.d.s. groups, respectively. None resulted in discontinuation of treatment. Overall primary resistance of H. pylori against metronidazole was found in 22 of 116 strains (19%).
Conclusions: The combination of omeprazole, amoxycillin and metronidazole achieves about an 80% cure rate of H. pylori infection even in active ulcers. The total daily dose, and the choice of twice or three times daily dosing does not seem critical with this regimen.