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Sequential Therapy vs Standard Triple-Drug Therapy for Helicobacter pylori Eradication
Abstract & Commentary
By Malcolm Robinson MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson reports no relationship to this field of study.
Synopsis: Standard 10 day triple therapy for Helicobacter pylori may result in relatively low eradication rates. An alternative regimen of PPI plus amoxicillin for 5 days followed by PPI plus clarithromycin plus tinidazole for five days seems to provide significantly better H. pylori eradication.
Source: Vaira Dino, et al. Ann Inter Med. 2007;1466:556-563.
The somewhat inexplicable but enormous enthusiasm for the eradication of H. pylori has been discussed many times in Internal Medicine Alert in the medical literature, and in numerous lay publications. Although H. pylori infection certainly is associated with gastric and duodenal ulcers, MALT lymphomas, and gastric cancer, most of these disorders have progressively decreased in the United States. However, H. pylori remains classified by the World Health Organization as a Class I carcinogen. If eradication is to be accomplished (and it can be quite difficult), physicians should employ the regimen most likely to be successful. H. pylori infections are becoming resistant to metronidazole and clarithromycin. As a result, eradication rates attained with currently employed regiments are falling in most western countries.
A better therapeutic option is clearly needed. Several small studies have suggested that a novel 10-day sequential regimen could improve results. The present study evaluates this concept in 300 patients presenting with dyspepsia who were determined to have H. pylori infection by urea breath testing. Patients also were required to have at least 2 of the following tests positive for H. pylori: rapid urease testing on biopsy specimens, histological examination of the antral biopsies, and/or culture of the biopsy specimens. Patients had not previously received H. pylori treatment or any PPIs or H2 receptor antagonists, bismuth preparations or antibiotics. No patients were taking ketoconazole or anticoagulants. Half received a standard 10-day regimen of pantoprazole 40 mg, 500 mg clarithromycin, and 1 gram of amoxicillin, all given twice daily. The other 150 patients received 40 mg of pantoprazole and 40 mg of amoxicillin twice daily for 5 days followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole twice daily for a second five day period. The conventional 10-day regimen produced 77% eradication of H. pylori vs 89% eradication in the group with the sequential regimen.
In the 143 patients evaluated in the "per protocol" analysis of the sequential group (completed all phases of therapy exactly as the protocol demanded), the eradication rate was 93% vs 79% in the 10-day triple therapy group (n = 146 per protocol). Rates of adverse events (some quite common) were equal in the 2 groups studied, but few patients withdrew (3 patients in the sequential group and 2 patients in those getting standard therapy). This study was performed in two large Italian hospitals, and the authors note that the results may or may not be applicable to H. pylori in other settings. The authors propose several plausible bacteriological explanations for the results, including the fact that tinidazole was added to the sequential therapeutic mix (tinidazole is a drug similar to metronidazole).
This study suggests that there are likely to be a number of new approaches to the eradication of H. pylori including sequential regimens such as the one utilized in this study. It is probably too soon for us to adopt this approach until additional studies have been completed including clinical trials in North American settings and populations. As these authors comment, part of their success is undoubtedly due to the careful follow-up and detailed patient instructions intrinsic to a well run clinical trial. Similar results may not necessarily be attainable in the usual clinical practice setting, particularly in view of the annoying side effects present in all H. pylori eradication regimens (eg, taste perversion, diarrhea, and epigastric discomfort). Also, most North American physicians should think twice before attempting to identify or treat H. pylori except in ulcer patients and other even smaller groups that can reasonably be anticipated to profit from eradication. Treating nonulcer dyspeptic patients for H. pylori is usually quite disappointing in North America where symptoms frequently persist despite effective eradication.