Quadruple or triple therapies for helicobacter pylori - Tips from Other Journals

Author: Richard Sadovsky
Date: March 1, 2003

Treatment for Helicobacter pylori infection involves eradication with a multidrug regimen. Initially, bismuth-based, triple-drug, two-week regimens were used, but these regimens were rapidly followed by proton pump inhibitor (PPI)-based therapies that have been demonstrated to be effective in a one-week regimen. Quadruple-drug therapy using a PPI with bismuth triple therapy recently has been recommended to decrease rates of treatment failure caused by resistance to metronidazole or clarithromycin. Eradication therapy is being used more frequently in H. pylori-infected, non-endoscoped patients and in those with nonulcer dyspepsia. Treatment recommendations involving quadruple therapy versus PPI triple therapy in patients with nonulcer dyspepsia should be examined. Katelaris and associates randomized patients with endoscopically documented nonulcer dyspepsia and confirmed H. pylori infection to receive one of three treatments.

This study was undertaken in Australia, where there is a relatively high rate of metronidazole resistance. Clarithromycin resistance, although present, is much less common. Group 1 received PAC7 treatment (see accompanying table), group 2 received PBTM7 treatment, and group 3 received BTM14 treatment. Patients were seen again at week 2 to determine compliance with medications and at week 8 to retest for H. pylori.

Eradication of H. pylori infection occurred at a similar rate in groups 1 and 2, and at a significantly lower rate in group 3. Adverse effects were common although relatively minor, with patients reporting nausea, taste disturbance, headache, and diarrhea. More severe adverse effects occurred with BTM14 therapy, causing a higher rate of discontinuation of therapy in group 3.

The authors conclude that the efficacy of the PPI-based, triple-drug therapy used in this study is similar to that of common quadruple-drug regimens. Bismuth triple therapy taken for two weeks had a lesser efficacy rate and more adverse effects, making it a poorer first-line treatment choice. When metronidazole resistance was considered, PPI added to bismuth-based triple therapy appeared to overcome drug resistance and allowed the use of a one-week regimen. Two-week bismuth triple therapy is probably obsolete as a first-line treatment. Quadruple therapy may be the preferred first-line treatment when clarithromycin resistance rates are high, and the latter is likely to occur more often in the future.

EDITOR'S NOTE: The value of H. pylori eradication in patients with nonulcer dyspepsia remains unclear. Recent studies continue the debate, with a large British study finding that H. pylori eradication in patients on long-term treatment for dyspepsia reduced the need for acid suppression and improved the quality of life and severity of dyspepsia symptoms (Verma S, Giaffer MH. Helicobacter pylori eradication ameliorates symptoms and improves quality of life in patients on long-term acid suppression. Dig Dis Sci July 2002; 47:1567-74). Almost 50 percent of the patients in this study had peptic ulcer disease, a recognized indication for H. pylori eradication. A smaller, Irish study also documented increased symptom resolution and prevention of disease progression in patients with nonulcer dyspepsia and H. pylori infection who were negative for infection after treatment (McNamara D, et al. Does Helicobacter pylori eradication affect symptoms in nonulcer dyspepsia: a 5-year follow-up study. Helicobacter October 2002;7: 317-21).

Other studies have shown no improvement in dyspepsia symptoms following successful H. pylori treatment (Gisbert JP, et al. Helicobacter pylori infection and functional dyspepsia. Meta-analysis of efficacy of eradication therapy [in Spanish]. Med Clin [Barc] March 2002;118:405-9, and Laine L, Dhir V. Helicobacter pylori eradication does not worsen quality of life related to reflux symptoms: a prospective trial. Aliment Pharmacol Ther June 2002;16:1143-8).

The Cochrane Systemic review database concludes that H. pylori eradication has a modest benefit in resolving nonulcer dyspepsia symptoms and that more study is needed. A recent primary care study in Canada confirmed relief of nonulcer dyspepsia with H. pylori eradication (Chiba N, et al. Treating Helicobacter pylori in primary care patients with uninvestigated dyspepsia: the Canadian adult dyspepsia empiric treatment-Helicobacter pylori positive (CADET-Hp) randomised controlled trial. BMJ April 27, 2002; 324:1012-6). The evidence in favor of H. pylori eradication in nonulcer dyspepsia looks good, but further studies are needed to examine the cost-effectiveness of this strategy.--R.S.

RELATED ARTICLE: "Per protocol" analysis of helicobacter pylori regimens

Group 1-PAC7 (82 percent eradication)All agents taken for seven days: Pantoprazole, 40 mg twice daily Amoxicillin, 1000 mg twice daily Clarithromycin, 500 mg twice dailyGroup 2-PBTM7 (88 percent eradication)All agents taken for seven days: Pantoprazole, 40 mg twice daily Bismuth subcitrate, 108 mg four times daily Tetracycline, 500 mg four times daily Metronidazole, 200 mg three times daily and 400 mg at nightGroup 3-BTM14 (74 percent eradication)All agents taken for 14 days: Bismuth subcitrate, 108 mg four times daily Tetracycline, 500 mg four times daily Metronidazole, 200 mg three times daily and 400 mg at nightSadovsky, RichardKatelaris PH, et al. A randomized comparison of quadrupleand triple therapies for Helicobacter pylori eradication:the QUADRATE study. Gastroenterology December 2002;123:1763-9.

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