Effects of Combination Therapy with Omeprazole and an Antibiotic on Helicobacter pylori and Duodenal Ulcer Disease

Abstract

Many gastroenterologists now advocate eradication of Helicobacter pylori for the prevention of recurrent peptic ulcer. However, no treatment has proved entirely successful. Triple therapy, in which a bismuth preparation and a nitroimidazole, such as metronidazole, are combined with another antibiotic, produces frequent adverse events, which reduce patient compliance. This treatment is also compromised by the potential for development of resistance to metronidazole. Resistance to metronidazole frequently develops when it is given alone and, although this acquired resistance is decreased by the addition of bismuth, the eradication rate with triple therapy, following good compliance, is still reduced to 61% in patients with metronidazole-resistant strains (1). Early studies suggest that omeprazole given in combination with an appropriate antibiotic, such as amoxycillin, eradicates the bacterium in a large proportion of patients (2, 3). Unlike triple therapy, this treatment is well tolerated, provides predictable and rapid symptom relief and ulcer healing, and is not associated with the development of resistance.

The efficacy of a combination of omeprazole and amoxycillin in the eradication of H. pylori and treatment of recurrent duodenal ulcer was compared with that of omeprazole alone in a double-blind, multicentre study. The study design is outlined in Fig. 1. A total of 248 patients with active duodenal ulcer from 9 Swedish centres were randomized in a ratio of 2:1 to receive either 40 mg omeprazole once daily for 2 weeks, followed by 40 mg omeprazole once daily plus 750 mg amoxycillin twice daily for 2 weeks, or 40 mg omeprazole once daily for 2 weeks, followed by 40 mg omeprazole once daily plus placebo for 2 weeks.

Endoscopy and laboratory assessments were carried out before entry into the study and at 1 and 6 months after cessation of therapy (or earlier in the case of symptomatic relapse). H. pylori status was determined by culture from four biopsy specimens taken from the antrum and by histological examination of six biopsy specimens, two each taken from the corpus, antrum, and duodenum. A patient was regarded as H. pylori-positive if any specimen from any site was positive. Eradication of H. pylori was defined as absence of H. pylori 1 month after cessation of therapy.

H. pylori was eradicated in 84 (54%) of the patients treated with omeprazole and amoxycillin and in 74% of the patients receiving this combination who took at least 90% of their medication. By contrast

H. pylori was not found in 4% of the patients who received omeprazole and placebo (see Table I). The difference between the two treatment groups was highly significant (p <0.0001; Mantel-Haenszel test). Of the 84 patients who were H. pylori-negative at 1 month of follow-up, only 3 were H. py/ori-positive at their last follow-up (6 months or earlier in the case of symptomatic relapse).

After 6 months, 70% of the patients treated with omeprazole and amoxycillin were in remission, irrespective of eradication, compared with only 36% of those who received omeprazole and placebo, as shown in Table II. Of the patients who became H. pylori-negative, 84% remained in remission throughout the 6-month follow-up period, and only one patient (1%) had an ulcer relapse during 1-6 months of follow-up.

A 12-month follow-up assessment was performed in 83 of the 135 patients who were in remission after 6 months. None of the patients who received omeprazole and amoxycillin had relapsed, whereas three patients who received omeprazole and placebo had a symptomatic relapse.

Both treatment regimens were well tolerated. Diarrhoea was the most commonly reported adverse event, occurring in 3.7% of the patients receiving omeprazole and amoxycillin and in 2.4% of the patients receiving omeprazole and placebo. Skin reactions occurred in 10 of the patients treated with omeprazole and amoxycillin. This required drug withdrawal in three patients. Therefore, in patients with suspected penicillin allergy, this treatment should be used with caution.

The results of this study show that eradication of H. pylori with a combination of omeprazole and amoxycillin eradicates the bacterium in most patients with duodenal ulcer and is effective in preventing ulcer relapse. Such therapy provides rapid pain relief, ulcer healing, and eradication of the bacterium in a single step; this simplified regimen is well tolerated and carries no risk of resistance, making it an ideal candidate for first-choice ulcer treatment. The mechanism underlying the synergistic effect between omeprazole and amoxycillin remains to be clarified, but it is probably multifactorial. To establish the optimal dose regimen and formulation for the combination of omeprazole and amoxycillin, additional studies are being undertaken.

Key Words:

• Amoxycillin
• duodenal ulcer
• Helicobacter pylori
• omeprazole
• ulcer relapse