Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Amoxicillin and omeprazole to eradicate Helicobacter pylori

ACP J Club. 1993 July-Aug;119:10. doi:10.7326/ACPJC-1993-119-1-010


Source Citation

Bayerdörffer E, Mannes GA, Sommer A, et al. High dose omeprazole treatment combined with amoxicillin eradicates Helicobacter pylori. Eur J Gastroenterol Hepatol. 1992 Sep;4:697-702.


Abstract

Objective

To study the safety and efficacy of amoxicillin added to high-dose omeprazole for eradication of Helicobacter pylori in patients with duodenal ulcers.

Design

Randomized, double-blind, controlled trial with median 9-month follow-up.

Setting

4 university clinics in Germany.

Patients

60 consecutive patients with a duodenal ulcer ≥ 5 mm in diameter were enrolled, and 53 finished the study (median age 48 y, 38 men). Exclusion criteria were gastric or pyloric ulcers; use of bismuth compounds or antibiotics during the previous 4 weeks; regular use of corticosteroids, nonsteroidal anti-inflammatory drugs, or > 100 mg of aspirin; previous ulcer surgery; pregnancy; renal insufficiency; allergies to penicillins; or contraindications to endoscopic biopsy.

Intervention

30 patients were randomized to receive omeprazole, 40 mg, twice daily for 10 days. 30 were randomized to receive both omeprazole, 40 mg, and amoxicillin, 1000 mg, twice daily for 10 days. Both groups then took omeprazole, 20 mg, each morning for 6 weeks.

Main outcome measures

Each patient had 4 endoscopies to biopsy the antrum and corpus. H. pylori was confirmed by histologic and culture findings. Gastritis and H. pylori colonization were graded on 4-point scales. Daily diaries and telephone interviews were used to collect data on adverse effects and compliance.

Main results

At the end of treatment, the groups did not differ for duodenal ulcer healing or for absence of adverse effects (25 of 26 patients taking omeprazole were healed and had no side effects vs. 27 of 27 patients taking both drugs). Patients who took both omeprazole and amoxicillin, compared with patients who took omeprazole alone, had a higher rate of clearance of H. pylori at the end of treatment (85% vs. 27% {95% CI for the 58% difference 37% to 80%}*; P < 0.001); a higher rate of eradication of H. pylori 4 weeks after treatment (82% vs. 0% {CI for the difference 67% to 97%}*; P < 0.001); and a lower rate of relapse for duodenal ulcers at 9 months (0% vs. 48% {CI -28% to -65%}*; P < 0.001). (* Numbers calculated from data in article.)

Conclusions

Omeprazole in combination with amoxicillin, compared with omeprazole alone, did not differ for duodenal ulcer healing or adverse effects. Patients taking both drugs had greater rates of H. pylori clearance immediately after treatment and had eradication 4 weeks later. Patients in whom H. pylori was eradicated did not experience ulcer relapse.

Sources of funding: In part, Astra; Grünenthal; and Becton and Dickinson.

For article reprint: Dr. E. Bayerdörffer, Klinikum Grosshadern, Universität München, Marchioninistrasse 15, 8000 München 70, Germany. FAX 49-89-21-802322.


Commentary

Because bismuth preparations favorably affect ulcer recurrence rates, relieve dyspeptic symptoms, and possess antimicrobial activity, they were included in the initial regimens developed to treat H. pylori gastritis. The observation that the eradication of H. pylori with bismuth-containing treatment regimens prevented the recurrence of associated ulcers led some investigators to conclude that this phenomenon was caused by special mucosal protective properties of bismuth and not the eradication of H. pylori.

Recently, Hentschel and colleagues reported a well-conducted H. pylori treatment study that did not include a bismuth preparation and showed the elimination of ulcer recurrence with the eradication of H. pylori (1). The results of the present study by Bayerdörffer and colleagues confirm these findings. These 2 studies provide compelling evidence against the idea that the mucosal protective properties of bismuth are responsible for the observed prevention of ulcer recurrence.

The initial attempts to eradicate H. pylori with amoxicillin alone produced eradication rates no better than 10% to 15%, even when high doses of amoxicillin were used (2). The Bayerdörffer study shows that the combination of amoxicillin and the proton pump inhibitor, omeprazole, achieves H. pylori eradication rates comparable to traditional bismuth-containing triple-agent therapy. Why does this occur with omeprazole? Perhaps H. pylori cannot survive the high pH environment created by omeprazole,or possibly omeprazole possesses intrinsic anti-H. pylori activity. This question remains to be answered.

The Bayerdörffer regimen may be safe, but the dose change in omeprazole at 10 days and the 6-week duration do not qualify it as simple. Outside of a university research setting, compliance may be a problem.

James S. Barthel, MD
University of Missouri Columbia, Missouri, USA