What is the most effective regimen for eradication of Helicobacter pylori in patients who have failed a first eradication attempt?

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Hojo M, Miwa H, Nagahara A, Sato N. Pooled analysis on the efficacy of the second-line treatment regimens for Helicobacter pylori infection. Scand J Gastroenterol. 2001; 36:690-700.



BACKGROUND: Based on randomized clinical trials (RCTs), the most effective first-line eradication therapy for Helicobacter pylori is a combination of proton pump inhibitor (PPI) and 2 antimicrobial agents.1 Yet there remains a significant treatment failure rate of 5% to 25%. Antibiotic resistance is the major impediment of cure.2 Using a pooled analysis approach, the authors determined the second-line treatment strategy resulting in the greatest percentage of H pylorieradication.

POPULATION STUDIED: Studies of H pylori re-eradication in adults were retrieved from MEDLINE database, reference lists of retrieved research papers, and major congress abstract lists. All studies were performed between 1994 and 1999, were conducted prospectively (or without information on study design), contained detailed information on eradication agents, and included subjects with only one treatment failure. Eighteen articles and 47 abstracts were identified; 16 articles and 24 abstracts met the inclusion criteria.

STUDY DESIGN AND VALIDITY: The authors performed a pooled efficacy analysis of re-treatment regimens for H pylori eradication in adults. They included all prospective studies—randomized and nonrandomized—that reported eradication rates in patients previously treated with antibiotic therapy. The inclusion criteria were appropriate, and the search for relevant articles was complete in that the authors included abstracts from international gastroenterology meetings. An analysis strategy of simple pooling was used (total number of patients successfully treated divided by all those enrolled in given treatment category), which is appropriate since the primary outcome was the eradication rate.

OUTCOMES MEASURED: The authors calculated a pooled eradication rate with 95% confidence intervals for each of the 6 general treatment categories. They also determined the eradication rate of each second treatment, accounting for differences in initial treatment therapy regimen. Finally, they ascertained if the effectiveness of second-line therapy regimens improved when distinct antimicrobials not used in the first attempt at treatment were used.

RESULTS: The most effective second-line therapies for eradication of H pylori were quadruple therapy, either ranitidine-bismuth-based triple therapy (ranitidine-bismuth product plus 2 antimicrobials) at 80.2% (95% confidence interval [CI], 75%-85%) or H2-blocker or PPI, bismuth compound, and 2 antimicrobials) at 75.8% (95% CI, 73%-79%). The second-line treatment eradication rate was lower when the initial therapy was a PPI with 2 antimicrobials versus a PPI with one antimicrobial. Re-treatment was more difficult with an increased number of antimicrobials used in initial therapy. The re-treatment eradication rate was greater when 2 new antimicrobials were included in the regimen than when a single new antimicrobial was added (P=.0064).


If initial attempts fail at eradication of H pylori then quadruple therapy (an antisecretory agent, a bismuth compound, and 2 antimicrobials) or ranitidine-bismuth (Tritec) plus 2 antimicrobials is the most effective follow-up treatment. The latter approach is fairly expensive ($150). For patients whose first course included only one antimicrobial, using 2 new antimicrobials is just as effective as quadruple or ranitidine bismuth-based therapy. These approaches will achieve eradication in 75% to 80% of resistant cases.

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