What is the recommended treatment regimen for a patient with a confirmed diagnosis of Helicobacter pylori (H. pylori) infection?

Treatment of H. pylori Infection

Bismuth quadruple therapy (BQT) for 14 days is the definitive first-line treatment for confirmed H. pylori infection. 1, 2, 3

First-Line Treatment Regimen

The preferred empiric first-line regimen consists of: 1, 2, 3

• Proton pump inhibitor (PPI) twice daily (high-dose dosing mandatory)
• Bismuth subcitrate/subsalicylate ~300mg four times daily
• Metronidazole 500mg three times daily
• Tetracycline 500mg four times daily
• Duration: 14 days (mandatory—never use 7-day regimens)

This recommendation comes from the American College of Gastroenterology and American Gastroenterological Association, who endorse BQT as the preferred empiric treatment when antibiotic susceptibility is unknown. 1, 2, 3 The rationale is compelling: BQT avoids clarithromycin entirely (where resistance rates are rising) and maintains high eradication rates despite antibiotic resistance patterns, which is the most important factor responsible for eradication failure. 1, 3

Critical Treatment Principles

Treatment duration and PPI dosing are non-negotiable: 1, 2, 3

• 14-day duration is superior to 7 days and significantly improves eradication rates regardless of regimen chosen
• High-dose PPI (twice daily) increases eradication success by approximately 5% compared to standard dosing
• Standard PPI doses: pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, rabeprazole 20mg 2

Patient adherence is the second most critical factor after antibiotic resistance—incomplete treatment leads to antibiotic resistance and treatment failure. 1, 2, 3 Counsel patients explicitly about completing the full 14-day course.

Alternative First-Line Regimens (When BQT Cannot Be Used)

In low clarithromycin resistance areas (<15% local resistance), PPI-clarithromycin-amoxicillin triple therapy for 14 days can be used, but this is increasingly uncommon in North America. 2 The FDA-approved regimen for H. pylori includes triple therapy with 1 gram amoxicillin, 500mg clarithromycin, and 30mg lansoprazole, all given twice daily for 14 days. 4

Second-Line Treatment After First-Line Failure

After failure of initial therapy: 1, 3

• Optimized bismuth quadruple therapy for 14 days is the preferred second-line regimen if BQT was not used previously
• Levofloxacin-containing triple therapy for 14 days is an alternative (levofloxacin 500mg once daily, amoxicillin 1g twice daily, PPI twice daily), though rising levofloxacin resistance rates must be considered 1, 3

The key principle: never repeat the same regimen that failed. 5

Confirmation of Eradication (Test-of-Cure)

All patients must undergo test-of-cure at least 4 weeks after completing treatment. 2, 3 This is mandatory to ensure successful eradication and prevent complications, particularly gastric cancer risk. 3

Preferred non-invasive testing methods: 3

• Urea breath test (UBT): 88-95% sensitivity, 95-100% specificity
• Laboratory-based validated monoclonal stool antigen test: >90% sensitivity and specificity

Critical pitfall: PPIs must be discontinued at least 2 weeks before testing to avoid false-negative results from bacterial suppression. 2, 3 Antibiotics and bismuth require similar washout periods. 1, 2, 3

Special Populations

Penicillin allergy: 1, 2

• Bismuth-containing quadruple therapy is recommended in high clarithromycin resistance areas (already contains no penicillin)
• In low clarithromycin resistance areas, PPI-clarithromycin-metronidazole for 14 days can be used

Pediatric patients: 1

• Tetracycline should not be used in children under 8 years due to risk of permanent tooth discoloration and impaired bone growth
• Fluoroquinolones should be avoided in children due to risk of cartilage damage and tendon rupture

Peptic ulcer disease with bleeding: 3

• Start eradication therapy after 72-96 hours of intravenous PPI administration
• Eradication reduces ulcer recurrence risk by >90%

Key Clinical Pitfalls to Avoid

Never perform H. pylori testing while patients are taking: 1, 2, 3

• PPIs (discontinue ≥2 weeks before testing)
• Antibiotics (discontinue ≥4 weeks before testing)
• Bismuth (discontinue ≥4 weeks before testing)

Bacterial suppression from these medications yields false-negative results, leading to missed diagnoses. 1, 2, 3

Antibiotic resistance is the most important factor responsible for eradication failure—local surveillance of resistance patterns is mandatory for optimal treatment selection. 1, 2, 3 This is why BQT is preferred: it avoids clarithromycin, where resistance rates are highest and most problematic.

Post-Eradication Expectations

Many patients will have residual dyspeptic symptoms after successful H. pylori eradication, particularly those with functional dyspepsia. 1 The primary benefit of eradication is elimination of peptic ulcer mortality risk and prevention of gastric cancer, not necessarily symptom resolution. 1 Residual symptoms should be managed with empirical acid suppression therapy (PPIs) if epigastric pain predominates. 1