What is the recommended triple therapy regimen for Helicobacter pylori (H. pylori) treatment?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 13, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Recommended Triple Therapy for H. pylori Infection

The recommended first-line triple therapy for H. pylori infection is a 14-day regimen of proton pump inhibitor (PPI) twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily, but this should only be used in areas with low clarithromycin resistance (<15-20%). 1

First-Line Treatment Options

  • In areas with high clarithromycin resistance (>15-20%), bismuth quadruple therapy is strongly recommended as first-line treatment, consisting of PPI twice daily, bismuth subsalicylate, metronidazole (400-500 mg), and tetracycline (500 mg) for 14 days 1, 2

  • Triple therapy with PPI, clarithromycin, and amoxicillin (PCA) or metronidazole (PCM) is equivalent in efficacy when clarithromycin resistance is low 1

  • The FDA-approved dosage for H. pylori triple therapy is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily for 14 days 3

  • Concomitant non-bismuth quadruple therapy (PPI, amoxicillin, metronidazole, and clarithromycin) is an alternative first-line option in areas with high clarithromycin resistance where bismuth is not available 1

Optimizing Triple Therapy Efficacy

  • High-dose PPI (twice daily) significantly increases the efficacy of triple therapy by approximately 6-10% compared to standard doses 1

  • Extending treatment duration from 7 to 14 days improves eradication success by approximately 5% 1

  • The best approach is to succeed on the first attempt to avoid retreating and retesting, reducing cost, anxiety, and negative impacts on gut microbiota 1

  • Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 3

  • Certain probiotics may help reduce side effects of treatment, though evidence for this is limited 1, 2

Alternative Regimens

  • Dual therapy with amoxicillin (1 gram) and lansoprazole (30 mg), each given three times daily for 14 days, is an FDA-approved alternative for patients allergic or intolerant to clarithromycin 3

  • Sequential therapy (5 days of PPI + amoxicillin, followed by 5 days of PPI + clarithromycin + metronidazole) is considered a non-ideal option by the American College of Gastroenterology 1

  • Levofloxacin-based triple therapy is generally not recommended as first-line therapy but can be considered in areas with high dual resistance (clarithromycin and metronidazole) and low levofloxacin resistance 1, 4

Second-Line and Rescue Therapies

  • After failure of clarithromycin-based triple therapy, bismuth quadruple therapy or levofloxacin-containing triple therapy are recommended 1, 2

  • Rifabutin-containing therapy (PPI, amoxicillin, rifabutin) is considered an option for third or fourth-line treatment 1, 4

  • Antimicrobial susceptibility testing should guide therapy whenever possible after two treatment failures 2, 4

Important Considerations and Pitfalls

  • Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance is likely to have developed 2, 5

  • Local resistance patterns should guide therapy choice - triple therapy is ineffective when clarithromycin resistance exceeds 15-20% 1

  • Bismuth is valuable because bacterial resistance to this compound is extremely rare, and bismuth quadruple therapy is effective even against strains resistant to metronidazole 2, 5

  • Confirm eradication after treatment using either urea breath test or a validated monoclonal stool test (not serology) 1, 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Treatment for Helicobacter pylori Infection

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

ACG Clinical Guideline: Treatment of Helicobacter pylori Infection.

The American journal of gastroenterology, 2024

Guideline

Tratamiento de H. pylori con Subsalicilato de Bismuto

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.