1-week treatment with colloidal bismuth subcitrate, tetracycline, and metronidazole with 4-weeks of omeprazole eradicated Helicobacter pylori in patients with duodenal ulcer
ACP J Club. 1993 Jan-Feb;118:10. doi:10.7326/ACPJC-1993-118-1-010
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Hosking SW, Ling TK, Yung MY, et al. Randomised controlled trial of short term treatment to eradicate Helicobacter pylori in patients with duodenal ulcer. BMJ. 1992 Aug 29;305:502-4.
To determine whether treatment for 1 week with colloidal bismuth subcitrate, tetracycline, and metronidazole in conjunction with omeprazole is sufficient to eradicate Helicobacter pylori in patients with duodenal ulcer.
Randomized, single-blind, controlled trial of 8 weeks duration.
Specialized ulcer clinic in a teaching hospital in Hong Kong.
155 patients (median age 41 y, 111 men) with a urease-positive biopsy and an endoscopically confirmed duodenal ulcer that had bled within the previous 24 hours (51 patients) or was causing dyspepsia (104 patients). Exclusion criteria were hemodynamic instability, previous surgery for acid reduction, or pregnancy. 146 patients (94%) completed the study.
Patients received either omeprazole for 4 weeks plus colloidal bismuth subcitrate (120 mg), tetracycline (500 mg), and metronidazole (400 mg), all 4 times daily for the first week (n = 78), or omeprazole alone for 4 weeks (n = 77). Drug treatment was started within 24 hours of baseline endoscopy.
Main outcome measures
Eradication of H. pylori, defined as failure to detect the organism by culture; presence of duodenal ulcer on endoscopic assessment; and side effects as reported by the patient. The follow-up assessment was conducted at 8 weeks, 4 weeks after all treatment had ended.
H. pylori was eradicated more often in patients receiving all 4 drugs than in those taking omeprazole alone (P < 0.001) (Table). Endoscopically confirmed duodenal ulcers were present less often in patients taking all 4 drugs than in those treated with omeprazole alone (P < 0.01) (Table). Most duodenal ulcers occurred in patients who had presented with dyspepsia rather than bleeding, but the result was not statistically significant. Mild dizziness was reported by 6 patients in each treatment group, but this did not affect compliance.
A 1-week treatment with colloidal bismuth subcitrate, metronidazole, and tetracycline, in conjunction with a 4-week course of omeprazole, was effective and safe in eradicating Helicobacter pylori and in reducing the frequency of duodenal ulcers 4 weeks after treatment ended.
Source of funding: Croucher Foundation.
For article reprint: Professor A. K. Li, Department of Surgery, Prince of Wales Hospital, Shatin, Hong Kong. FAX 852-786-3629.
Table. Omeprazole plus colloidal bismuth subcitrate, tetracycline, and metronidazole (4 drugs) vs omepazole alone in patients with duoenal ulcer*
|Outcome at 8 weeks||4 drugs||Omepazole alone||RBI (95 % CI)||NNT (CI)|
|Eradication of Helicobacter pylori||95%||4%||2203% (726 to 6643)||2 (2 to 2)|
|RRR (CI)||NNT (CI)|
|Duodenal ulcers||5%||22%||75% (34 to 91)||6 (4 to 18)|
*Abbreviations defined in Glossary; RRR, RBI, NNT, and CI calculated from data in article.
Helicobacter pylori is the major etiologic factor in duodenal ulcer disease. Its eradication essentially eliminates duodenal ulcer recurrence (1). Triple drug regimens appear to be most effective for eradicating H. pylori and are typically administered for 1 to 2 weeks. Hosking and colleagues report success in eradicating H. pylori and healing active duodenal ulcers with a quadruple-drug regimen consisting of 3 antimicrobial agents given for just 1 week and an acid suppression agent given for 4 weeks.
The single-blind method used resulted from difficulties with blinding patients to bismuth therapy. Bismuth agents turn stool a green-black color that is difficult to mimic and impossible to eliminate. Because outcome measures were minimally subjective (culture results and endoscopically proved ulcers), single blinding was unlikely to bias the results.
Certain aspects of the study detract from its general applicability. First, patients consisted primarily of Chinese men who had duodenal ulcers with a lower prevalence of H. pylori (84%) and a higher prevalence of bleeding (42%) than might be expected in North Americans. Second, the absence of dyspepsia and nausea in patients receiving antimicrobial agents known to have these side effects is not entirely consistent with the experience of other investigators.
HELIDAC is the American version of the antibiotic-bismuth portion of this treatment regimen. It consists of tetracycline, metronidazole and bismuth subsalicylate packaged for a 2 week course of therapy. Prescription of each drug individually and as a generic for 1 week is the most cost-effective therapy available for H. pylori. The cost-effectiveness of tetracycline-metronidazole-bismuth therapy is particularly compelling in view of mounting evidence that the addition of a proton pump inhibitor (quadruple therapy) is not necessary for ulcer healing in uncomplicated ulcer disease (2, 3). However, continued use of a proton pump inhibitor would seem wise in complicated ulcer disease.
James S. Barthel, MD
University of Missouri School of MedicineColumbia, Missouri, USA