How should I treat Helicobacter pylori infection in a patient with gastro‑oesophageal reflux disease?

Treatment of H. pylori Infection in GERD Patients

Treat H. pylori infection in GERD patients who require long-term PPI therapy using standard eradication regimens; eradication prevents progression to atrophic gastritis without worsening reflux symptoms. 1, 2

When to Test and Treat H. pylori in GERD

Test for H. pylori in any GERD patient who will require long-term PPI maintenance therapy (typically defined as continuous use beyond 8-12 weeks), because prolonged acid suppression in H. pylori-positive patients accelerates the development of corpus-predominant gastritis and atrophic gastritis—a precancerous condition. 1, 2

• Do not test or treat H. pylori with the goal of improving GERD symptoms or preventing reflux complications—H. pylori status has no effect on symptom severity, recurrence, or treatment efficacy in GERD. 1

• Timing of testing: Test when you determine that maintenance PPI therapy will be needed, not necessarily before starting initial PPI treatment. 2, 3 Many GERD patients require only short-term therapy, so testing everyone upfront is unnecessary. 2

• For patients already on long-term PPIs: Offer H. pylori testing and eradication therapy regardless of how long they have been on acid suppression, because eradication fully reverses active gastritis even after years of PPI use. 2

Standard Eradication Regimens for GERD Patients

Use the same evidence-based H. pylori eradication protocols as for any other indication:

First-Line: Bismuth Quadruple Therapy (14 days)

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 4
• Bismuth subsalicylate 262 mg (2 tablets) four times daily 4
• Metronidazole 500 mg three to four times daily 4
• Tetracycline 500 mg four times daily 4

This regimen achieves 80-90% eradication rates even in areas with high clarithromycin resistance (>15%). 4

Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy (14 days)

Use only if bismuth is unavailable and local clarithromycin resistance is documented <15%:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg) 4
• Amoxicillin 1000 mg twice daily 4
• Clarithromycin 500 mg twice daily 4
• Metronidazole 500 mg twice daily 4

Avoid Standard Triple Therapy

Do not use PPI + clarithromycin + amoxicillin triple therapy empirically in most regions, as clarithromycin resistance now exceeds 15-20% in North America and most of Europe, reducing eradication rates to approximately 70%. 4

Key Treatment Principles

• 14-day duration is mandatory for all regimens—extending from 7 to 14 days improves eradication by approximately 5%. 4

• High-dose PPI twice daily (not once daily) increases cure rates by 6-12% compared to standard dosing. 4

• Take PPIs 30 minutes before meals on an empty stomach, without concomitant antacids. 4, 5

Confirming Eradication

Test-of-cure is mandatory in GERD patients on long-term PPIs to ensure the infection is cleared and prevent ongoing progression to atrophic gastritis:

• Perform urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy 4

• Discontinue PPI at least 2 weeks (preferably 7-14 days) before testing to avoid false-negative results 4

• Never use serology for test-of-cure, as antibodies persist long after successful eradication 4

Impact on GERD Management

Eradication does not worsen GERD or reduce PPI efficacy:

• Meta-analyses show no significant difference in symptomatic or erosive GERD after H. pylori eradication versus persistent infection, regardless of baseline disease or follow-up duration. 6

• H. pylori eradication does not exacerbate pre-existing GERD or affect PPI treatment efficacy. 1

• Continue PPI therapy at the same dose after eradication; adjust only based on GERD symptoms, not H. pylori status. 2

Critical Pitfalls to Avoid

• Do not defer H. pylori eradication in PPI-dependent GERD patients due to concerns about worsening reflux—this fear is not supported by evidence. 1, 6

• Do not use H. pylori eradication as a strategy to improve GERD symptoms—it will not help reflux control. 1

• Do not continue long-term PPIs in H. pylori-positive patients without eradicating the infection—this accelerates atrophic gastritis development. 1, 2

• Do not omit test-of-cure—persistent infection permits ongoing progression toward gastric cancer despite PPI therapy. 4

• Do not use once-daily PPI dosing during eradication therapy—twice-daily high-dose PPI is mandatory for optimal efficacy. 4