Library

Notes: Background. Helicobacter pylori eradication with omeprazole, amoxycillin, and metronidazole is both effective and inexpensive. However, eradication rates with different dosages and dosing vary, and data on the impact of resistance are sparse. In this study, three different dosages of omeprazole, amoxycillin, and metronidazole were compared, and the influence of metronidazole resistance on eradication was assessed.Methods. Patients (n = 394) with a positive H. pylori screening test result and endoscopy-proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada. After baseline endoscopy, patients were randomly assigned to treatment for 1 week with either omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 400 mg twice daily (low M); or omeprazole, 40 mg once daily, plus amoxycillin, 500 mg three times daily, plus metronidazole, 400 mg three times daily (medium M); or omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 800 mg twice daily (high M). H. pylori status at entry was assessed by a 13C urea breath test and a culture. Eradication was defined as two negative 13C-urea breath test results 4 and 8 weeks after therapy. Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy.Results. The eradication rates, in terms of intention to treat (ITT) (population n = 379) (and 95% confidence interval [CI]) were as follows: low M 76% (68%, 84%), medium M 76% (68%, 84%), and high M 83% (75%, 89%). By per-protocol analysis (population n = 348), the corresponding eradication rates were: low M 81%, medium M 80%, and high M 85%. No H. pylori strains were found to be resistant to amoxycillin. Prestudy resistance of H. pylori strains to metronidazole was found in 72 of 348 (21%) of the cultures at entry (range, 10%–39% in the five countries). The overall eradication rate in prestudy metronidazole-susceptible strains was 232 of 266 (87%) and, for resistant strains, it was 41 of 70 (57%; p 〈 .001). Within each group, the results were as follows (susceptible/resistant): low M, 85%/54%; medium M, 86%/50%; and high M, 90%/75%. There were no statistically significant differences among the treatment groups. 23 strains susceptible to metronidazole before treatment were recultured after therapy failed; 20 of these had now developed resistance.Conclusions. H. pylori eradication rates were similar (approximately 80%) with all three regimens. Metronidazole resistance reduced efficacy; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome. Treatment failure was generally associated with either prestudy or acquired metronidazole resistance. These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance.

Notes: Abstract The recognition of the role of Helicobacterpylori in the pathogenesis of peptic ulcer disease hasled to renewed interest in bismuth pharmacology sincebismuth compounds have both anti-Helicobacter pylori and ulcer healing properties. The precisechemical structure of current bismuth compounds is notknown. This has hindered the development of new andpotentially more efficacious formulations. We havecreated two new compounds,2-chloro1,3-dithia-2-bismolane (CDTB) and1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT), withknown structure. In a rat model of gastric ulceration,BTBT was comparable to, and CDTB was significantly less effective thancolloidal bismuth subcitrate in healing cryoprobeinducedulcers. However, both BTBT and CDTB inhibited H. pylorigrowth in vitro at concentrations 〈1/10 that of colloidal bismuth subcitrate. The effects onulcer healing are not mediated by suppression of acidsecretion, pepsin inhibition, or prostaglandinproduction. Since all treated animals received the same amount of elemental bismuth, it appears thatthe efficacy of bismuth compounds varies with compoundstructure and is not simply dependent on the delivery ofbismuth ion. Because the structure of the novel compounds is known, our understanding of therelationship of bismuth compound structure and tobiologic activity will increase. In the future it may bepossible to design other novel bismuth compounds with more potent anti-H. pylori and ulcer healingeffects.