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  • Review Article
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New concepts of resistance in the treatment of Helicobacter pylori infections

Nature Clinical Practice Gastroenterology & Hepatology volume 5, pages 321–331 (2008)Cite this article

Abstract

The prevalence of antimicrobial drug resistance is now so high that all patients infected with Helicobacter pylori should be considered as having resistant infections. Ideally, therapy should be based on pretreatment antibiotic-susceptibility testing but this strategy is not currently practical. At present, clarithromycin-containing triple therapies do not reliably produce a ≥80% cure rate on an intention-to-treat basis and are, therefore, no longer acceptable as empiric therapy. In this Review, we discuss concepts of resistance that have become part of mainstream thinking for other infectious diseases but have not yet become so with regard to H. pylori. We also put data on the pharmacokinetics and pharmacodynamics of the drugs used in H. pylori therapy and the effect of host cytochrome P450 genotypes in context with treatment outcomes. Our primary focus is to address the problem of H. pylori resistance from a novel perspective, which also attempts to anticipate the direction that research will need to take to provide clinicians with reliable approaches to this serious infection. We also discuss current therapies that provide acceptable cure rates when used empirically (i.e. sequential therapy; four-drug, three-antibiotic, non-bismuth-containing 'concomitant' therapy; and bismuth-containing quadruple therapy) and how they might be further improved.

Key Points

  • Traditional triple therapy remains effective only when used to treat infections with susceptible organisms

  • The prevalence of antibiotic resistance has increased to such an extent that, to maintain acceptable cure rates, all patients should be considered as having resistant infections

  • Therapies that do not reliably yield ≥90% cure rates on an intention-to-treat basis should not be prescribed empirically; triple therapies that contain combinations of a PPI, amoxicillin, clarithromycin or metronidazole now typically yield cure rates <80% and are no longer acceptable as empiric therapy

  • Initial empiric therapy options currently include the following: sequential therapy; concomitant, four-drug, antibiotic therapy; and bismuth-containing, high-dose metronidazole, quadruple therapy

  • Sequential and concomitant (i.e. four drugs, three of which are antibiotics) therapies have the potential to be improved by simple measures such as increasing the duration of treatment

  • High-dose, frequent-administration PPI therapy can reduce phenotypic resistance and should increase the cure rates achieved with amoxicillin-containing dual therapy into the acceptable range

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Figure 1: Results of comparison studies that included more than 100 patients and tested the combination of a PPI plus amoxicillin and clarithromycin.
Figure 2: Weighted means and 95% confidence intervals for H. pylori eradication rates in 16 studies of sequential therapy (n = 1,805) for 10 days58 and 9 studies of concomitant therapy (n = 715) for 3–7 days.60,61,62,63,64,65,66,67,68

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Acknowledgements

This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338, which funds the Texas Gulf Coast Digestive Diseases Center.

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Authors and Affiliations

  1. DY Graham is a Professor in the Departments of Medicine and Molecular Virology and Microbiology at the Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.,

    David Y Graham

  2. A Shiotani is an Associate Professor in the Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.,

    Akiko Shiotani

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Correspondence to David Y Graham.

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Competing interests

David Y Graham has received small amounts of grant support and/or free drugs or urea breath tests from Meretek Diagnostics, Jannsen/Eisai and TAP, and BioHit for investigator-initiated and completely investigator-controlled research. He is a consultant for Novartis in relation to vaccine development for the treatment or prevention of Helicobacter pylori infection. He is also a paid consultant for Otsuka Pharmaceuticals and a member of the Board of Directors of Meretek Diagnostics, the manufacturer of the 13C-urea breath test. He also receives royalties on the Baylor College of Medicine patent covering the HM-CAP serologic test. Akiko Shiotani declared no competing interests.

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Graham, D., Shiotani, A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 5, 321–331 (2008). https://doi.org/10.1038/ncpgasthep1138

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