COMBINATION AMOXICILLIN AND METRONIDAZOLE WITH FAMOTIDINE IN THE ERADICATION OF HELICOBACTER-PYLORI - A RANDOMIZED, DOUBLE-BLIND COMPARISONOF A 3 TIMES DAILY AND TWICE-DAILY REGIMEN

Objectives: To determine the efficacy of a three times daily (t. i. d. ) versus a twice daily (b. i. d.) regimen of combination amoxycillin a nd metronidazole and famotidine in the eradication of Helicobacter pyl ori and the influence of metronidazole resistance on the outcome of tr eatment. Patients: Patients selected had unequivocal evidence of H. py lori infection based on the urease test, culture and histology and had either peptic ulcer disease or non-ulcer dyspepsia. Design: The study was a comparative and double-blind study and patients were randomized to receive either amoxycillin 750 mg t. i. d. and metronidazole 500 m g t. i. d. for 12 days or amoxycillin 1000 mg b. i. d. and metronidazo le 500 mg b. i. d. for 12 days. Both groups also received famotidine 4 0 mg for 6 weeks. Main outcome measure: Patients were assessed for suc cessful eradication, defined as absence of bacteria in all tests, at l east 4 weeks after completion of antibiotic therapy by repeat gastrosc opy. Results: One hundred and twenty-nine patients were recruited for the study. Two patients defaulted follow-up, two patients were withdra wn from the study and six patients were found to be non-compliant with medications. The eradication rates of the t. i. d. regimen was higher than the b. i. d. regimen (per protocol (PP) analysis: 83.3% (50/60) vs. 76.3% (45/59), P = 0.337; intention-to-treat (ITT) analysis: 78.5% (51/65) vs. 75.0% (48/64), P = 0.642). Seventy-five patients had pre- treatment cultures checked for metronidazole resistance, 33 (44.0%) we re found to be resistant. Acquired resistance occurred in 3/40 (7.5%) patients. Eradication rates of metronidazole-sensitive and metronidazo le-resistant patients: t. i. d. regimen - 100% (17/17) and 88.2% (15/1 7), b. i. d. regimen -19/21 (90.5%) and 11/15 (73.3%). Side effects we re reported in up to 70% of patients but were mild and tolerable in th e majority. Two patients were withdrawn from the study because of a fi xed drug eruption in one and generalized macular rash in the other. Co nclusion: Combination amoxycillin and metronidazole is effective in er adicating H. pylori. There was a tendency for the t. i. d. regimen to be better than the b. i. d. regimen and for metronidazole-resistant in fections to be associated with a lower eradication rate but these diff erences did not reach statistical significance.