Highly effective twice-daily triple therapies for Helicobacter pylori infection and peptic ulcer disease: does in vitro metronidazole resistance have any clinical relevance?

OBJECTIVES

To compare cure rates of Helicobacter pylori (H. pylori) infection, ulcer healing, and side effects of three simplified regimens of triple therapy in patients with peptic ulcer disease.

METHODS

Two hundred thirty-one patients were prospectively randomized to receive either regimen OAM (omeprazole 20 mg b.i.d., amoxicillin 750 mg b.i.d., and metronidazole 400 g b.i.d.), OCM (omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d.), or BCM (bismuth subcitrate 240 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d.), all for 10 days. Side effects were reported immediately afterward in a self-administered questionnaire. Upper endoscopy was carried out before treatment and 2 months after treatment. Three antral and three corpus biopsy specimens were analyzed microbiologically and with rapid urease test to determine the presence of H. pylori. Altogether 143 patients (62%) had an active ulcer at start of treatment. Metronidazole resistant (M-R) H. pylori strains were found in 30% of patients, while none had clarithromycin resistant (C-R) strains.

RESULTS

According to intention-to-treat analysis, H. pylori cure rates were 91, 95, and 95% with OAM, OCM, and BCM, respectively (p = 0.63). In patients with metronidazole-sensitive (M-S) strains versus M-R strains, the cure rates were 96 versus 77% with OAM (p = 0.025), 94 versus 94% with OCM, and 94 versus 96% with BCM. Ulcer healing rates were 95, 94, and 92%, respectively (p = 0.91). There were no significant differences in side effects between the regimens, and only five patients (2%) had to stop the treatment prematurely.

CONCLUSIONS

All treatment regimens were highly effective for cure of H. pylori infection and for ulcer healing. Metronidazole resistance reduced the efficacy of OAM, but was of no importance for the efficacy of OCM or BCM. Side effects were of minor importance.