Tag: gastritis

Helicobacter pylori eradication therapy

~ Son of Pilgrim ~ Leave a comment

Originally published 18 October 2016. Revised October 2026.

Update, October 2026: I have revised this 2016 post. Bismuth quadruple therapy for 14 days, which was emerging as the new standard when I first wrote it, is now the first-line regimen recommended by the American College of Gastroenterology (2024), and clarithromycin triple therapy is no longer recommended unless the strain is known to be susceptible. Clarithromycin resistance in Australia has risen. I have also corrected the regimens, which in the original were listed incorrectly.

What are the current recommendations for management of H. pylori infection?

Why eradicate?

Chronic H. pylori gastritis progresses through recognisable stages, and the risk of gastric cancer rises with each. Serology (H. pylori antibody) combined with serum pepsinogen (PG) groups patients into four categories: A (HP negative, PG negative), B (HP positive, PG negative), C (HP positive, PG positive) and D (HP negative, PG positive, reflecting metaplastic gastritis). The annual incidence of gastric cancer in the figure below rises from about 0% in group A to about 0.1%, 0.25% and 1% in groups B, C and D.

Gastric Cancer Risk Diagnosis and Prevention in Subjects with Helicobacter pylori-related Chronic Gastritis: HP = H. pylori; PG = serum pepsinogen [Image: Intech Open]

Most infected people stay well, but a minority develop peptic ulcer disease, atrophic gastritis and intestinal metaplasia, and rarely gastric cancer or MALT lymphoma.

[Image Altered States]
[Figure 3: H. pylori virulence factors (flagella, urease, lipopolysaccharides, outer proteins, vacuolating toxin, type IV secretion system, secretory enzymes). Image: Primal Docs]

Choosing a regimen: resistance matters

Clarithromycin and metronidazole have high emergent resistance, and it helps to know the local pattern and whether the patient has had previous exposure to either drug.

  • Clarithromycin: primary resistance in Australia and New Zealand is about 7% overall but has risen, to about 16% in studies from the last 20 years. In patients who have already failed eradication therapy, resistance in recent Western and South Australian isolates was about 82%.
  • Metronidazole: about 50% primary resistance in the same pooled data, and about 68% after treatment failure.
  • Amoxicillin and tetracycline: resistance remains very low (under 0.5% for primary resistance, and amoxicillin about 4% and tetracycline 0.5% after treatment failure).
  • Levofloxacin: resistance was about 22% in the treatment-failure cohort, so it is not a reliable empirical choice. It may be used instead of clarithromycin but is less well tolerated and prone to rapid emergence of resistance.

First-line: bismuth quadruple therapy

Optimised bismuth quadruple therapy for 14 days is the recommended first-line regimen for treatment-naive patients (ACG 2024):

  • A proton pump inhibitor twice daily
  • Bismuth (subcitrate or subsalicylate) four times daily
  • Tetracycline 500 mg four times daily
  • Metronidazole 500 mg three or four times daily

Doxycycline should not be substituted for tetracycline. In patients with a penicillin allergy it is a good choice, because it contains no penicillin. Bismuth has historically been available in Australia only through the Special Access Scheme, so check current availability.

When clarithromycin triple therapy is still used

Standard triple therapy is a PPI + amoxicillin 1 g + clarithromycin 500 mg, each twice daily, for 7 to 14 days (a second week adds about 10% to eradication rates). It is acceptable only where clarithromycin resistance is low (below about 15 to 20%), and the 2024 ACG guideline advises against it unless the strain’s susceptibility is known, since eradication falls to about 30% in resistant strains.

A regimen combining a PPI with three antibiotics (amoxicillin, metronidazole and clarithromycin), as I described in 2016, is not a standard “triple”. It is a non-bismuth quadruple regimen, and it is suitable only where metronidazole resistance is low, which is not the Australian situation.

Once a patient has failed a clarithromycin-based regimen, it should not be repeated. Metronidazole and clarithromycin tend to fail on re-use, whereas amoxicillin, tetracycline and bismuth can be used again.

Probiotics

Probiotics have been claimed to reduce side effects and possibly improve eradication, but the evidence is not yet strong enough to recommend them routinely.

Conclusion

The current standard of care for H. pylori infection is 14-day bismuth quadruple therapy:

  1. a proton pump inhibitor, twice daily
  2. bismuth: Pepto-Bismol (bismuth subsalicylate; take care with concomitant NSAIDs and anticoagulants) or bismuth subcitrate
  3. tetracycline
  4. metronidazole

Confirm that the infection has been eradicated after treatment with a urea breath test or stool antigen test.

About the images. The three figures in this post are original schematic diagrams drawn for The Good Doctor. They are not reproductions of any published figure, and no photographs or third-party artwork have been used. The concepts are adapted from the sources linked in the captions and the references. The incidence figures in Figure 1 are approximate, and the outcome frequencies in Figure 2 are qualitative only. The diagrams are simplified for teaching and are not to scale. They are not a substitute for the primary literature or current guidelines, and they are not clinical advice.

References

  1. American College of Gastroenterology. Clinical Guideline: Treatment of Helicobacter pylori Infection (2024), as summarised in the ACG Evidence-Based GI commentary. https://gi.org/journals-publications/ebgi/schoenfeld_sep2024/
  2. World Gastroenterology Organisation. Global Guideline: Helicobacter pylori (2021). https://www.worldgastroenterology.org/UserFiles/file/guidelines/helicobacter-pylori-english-2021.pdf
  3. Antibiotic resistance of Helicobacter pylori in Australia and New Zealand: a systematic review and meta-analysis. https://researchnow.flinders.edu.au/en/publications/antibiotic-resistance-of-helicobacter-pylori-in-australia-and-new/
  4. Refractory Helicobacter pylori infection in Australia: updated multicentre study of antimicrobial resistance. https://research-repository.uwa.edu.au/en/publications/refractory-helicobacter-pylori-infection-in-australia-updated-mul/
  5. Helicobacter pylori eradication. Australian Family Physician, May 2014. https://www.racgp.org.au/afp/2014/may/helicobacter-pylori-eradication
  6. Helicobacter pylori Treatment: The ‘Rules’ Have Changed. Medscape, 30 August 2016.