What is the recommended first‑line therapy for Helicobacter pylori infection in an adult with gastro‑oesophageal reflux disease without macrolide allergy in a region of low clarithromycin resistance?

Treatment of H. pylori Infection in GERD Patients

In adults with GERD and H. pylori infection in a region of low clarithromycin resistance (<15%), the recommended first-line therapy is 14-day triple therapy consisting of a high-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred), clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily. 1, 2

First-Line Treatment Selection

When to Use Triple Therapy

• Triple therapy (PPI + clarithromycin + amoxicillin) is appropriate only when regional clarithromycin resistance is documented to be below 15%, as resistance above this threshold reduces eradication rates to approximately 70% or lower 1, 2
• The regimen consists of esomeprazole or rabeprazole 40 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily for 14 days 1, 2
• High-potency PPIs (esomeprazole or rabeprazole 40 mg) increase cure rates by 8-12% compared to standard-dose PPIs and should be taken 30 minutes before meals on an empty stomach 1, 2

Alternative First-Line Option

• Bismuth quadruple therapy for 14 days is an equally acceptable (and often superior) first-line choice, consisting of high-dose PPI twice daily, bismuth subsalicylate 262 mg four times daily, metronidazole 500 mg three to four times daily, and tetracycline 500 mg four times daily 1, 2
• This regimen achieves 80-90% eradication rates even in areas with high clarithromycin resistance and is not affected by clarithromycin or metronidazole resistance 1, 2

Critical Optimization Factors

Treatment Duration

• A 14-day course is mandatory for all regimens, as extending therapy from 7 to 14 days improves eradication success by approximately 5% 3, 1, 2, 4

PPI Dosing

• Twice-daily high-dose PPI is essential; once-daily standard dosing significantly reduces treatment efficacy 1, 4
• Avoid pantoprazole, as 40 mg provides acid suppression equivalent to only 9 mg of omeprazole 1

Antibiotic Selection

• Use amoxicillin (not metronidazole) as the second antibiotic in first-line triple therapy to preserve metronidazole for potential second-line quadruple therapy 5
• Never use amoxicillin-clavulanate; plain amoxicillin is the appropriate formulation 1

GERD-Specific Considerations

H. pylori Eradication and GERD Outcomes

• H. pylori eradication should not be performed with the intent to improve GERD symptoms or prevent reflux complications, as the infection does not cause or worsen GERD 5
• However, eradication is strongly recommended in GERD patients requiring long-term PPI therapy because chronic acid suppression combined with H. pylori infection accelerates the development of atrophic gastritis, a precursor to gastric cancer 5, 6
• Published intervention trials indicate that H. pylori treatment neither causes de novo esophagitis nor exacerbates existing reflux disease 5

Testing and Confirmation

• All GERD patients planned for long-term PPI therapy should be tested for H. pylori and treated if positive 5
• Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy, discontinuing PPI at least 2 weeks before testing 3, 1, 2

Second-Line Therapy After First-Line Failure

After Triple Therapy Failure

• Bismuth quadruple therapy for 14 days is the definitive second-line option, achieving 80-90% eradication even against clarithromycin-resistant strains 3, 1, 2
• Never repeat clarithromycin if it was in the failed regimen, as resistance develops rapidly and eradication rates drop from 90% to 20% with resistant strains 1, 2

Alternative Second-Line Option

• Levofloxacin triple therapy (PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily) for 14 days is acceptable only if the patient has no prior fluoroquinolone exposure 3, 1, 2

Common Pitfalls to Avoid

• Do not use standard triple therapy empirically if local clarithromycin resistance exceeds 15%, as this guarantees suboptimal outcomes 1, 2
• Do not shorten treatment duration below 14 days, as this reduces eradication by approximately 5% 3, 1, 2, 4
• Do not use once-daily PPI dosing; twice-daily high-dose administration is mandatory 1, 4
• Do not assume H. pylori eradication will improve GERD symptoms; treat the infection to prevent gastric cancer risk, not to manage reflux 5
• Do not skip test-of-cure, especially in patients requiring ongoing PPI therapy 3, 1, 5

Patient Factors Affecting Success

• Smoking roughly doubles the odds of treatment failure (OR 1.95); advise cessation during therapy 3, 1
• High BMI or obesity may reduce gastric mucosal drug concentrations, potentially lowering efficacy 3, 1
• Poor compliance is a leading cause of failure; provide clear instructions and emphasize completing the full 14-day course 1