Effect of two different doses of metronidazole and tetracycline in bismuth triple therapy on eradication of Helicobacter pylori and Its resistant strains
Classic triple therapy with bismuth, tetracycline and metronidazole is one of the most economic and effective regimens for the eradication of Helicobacter pylori. The aim of the study was to assess the efficacy of two different doses of tetracycline (TET) and metronidazole (MET) on cure of H. pylori infection and its MET-resistant strains. A total of 131 patients with duodenal ulcer were randomized into three groups and received the following medication for 2 weeks: group A, colloidal bismuth subcitrate (CBS) 3 x 120 mg + TET 3 x 500 mg + MET 3 x 250 mg/day; group B, CBS 3 x 120 mg + TET 3 x 500 mg + MET 3 x 125 mg/day; group C, CBS 3 x 120 mg + TET 3 x 250 mg + MET 3 x 125 mg/day. Control endoscopy was performed after 6 weeks. Two biopsy specimens from antral and three from corpus mucosa were taken for a urease test, histology and culture. Eradication was concluded if all three tests were negative for H. pylori. MET resistance was determined by the disc diffusion method. In total, 121 patients completed the study. Only two of the 43 patients in group A discontinued the therapy due to intolerance. Cure of H. pylori infection was achieved by per protocol analysis in 33 of 43 patients in group A (76.7%), in 20 of 40 patients in group B (50%) and in 20 of 38 patients in group C (52.6%) (P < 0.05 for A versus B or C). Forty-two out of 112 patients had H. pylori strains resistant to MET (42%). In each group, the cure rate of infection was higher in patients with MET-sensitive H. pylori than in MET-resistant H. pylori (80.7% versus 64.2% in group A, 60% versus 38.8% in group B and 52.6% versus 40% in group C, respectively). Increase of MET dose from 375 mg (in groups B and C) to 750 mg/day (in group A) seems to augment the eradication of MET-sensitive as well as MET-resistant strains (up from 52% to 84% and from 39% to 64%, respectively; P < 0.05). Cure rate of H. pylori infection under classic triple therapy remains unaffected by dose reduction of tetracycline but not of metronidazole. In countries with a high prevalence of metronidazole resistance, such as Iran, higher doses of metronidazole are probably needed to increase the cure rate of bismuth triple therapy.