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

Management of H. pylori Infection

Bismuth quadruple therapy for 14 days is the definitive first-line treatment for H. pylori infection in most clinical scenarios, achieving 80-90% eradication rates even in areas with high clarithromycin resistance. 1, 2

First-Line Treatment Regimens

Preferred: Bismuth Quadruple Therapy (14 days)

The most robust first-line option consists of: 1, 3

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, taken 30 minutes before meals) 1, 2
• Bismuth subsalicylate 262 mg (2 tablets) four times daily 1
• Metronidazole 500 mg three to four times daily (total 1.5-2 g/day) 1, 2
• Tetracycline 500 mg four times daily 1, 2

This regimen is superior because bacterial resistance to bismuth does not exist, and bismuth's synergistic effect overcomes metronidazole resistance even when present. 1, 2 The 14-day duration is mandatory—it improves eradication by approximately 5% compared to shorter regimens. 1, 2

Alternative First-Line: Rifabutin Triple Therapy (14 days)

For patients without penicillin allergy when bismuth is unavailable: 1, 3

• Rifabutin 150 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1

Rifabutin resistance remains rare, making this an effective alternative. 1, 2

When Triple Therapy May Be Considered

Only in areas with documented clarithromycin resistance below 15%: 1, 2

• PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days 1, 2

However, clarithromycin resistance now exceeds 15-20% in most of North America and Central, Western, and Southern Europe, making this option obsolete in most regions. 1, 2 When H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to approximately 20%. 1

Critical Optimization Factors

PPI Selection and Dosing

• Use esomeprazole or rabeprazole 40 mg twice daily—these increase cure rates by 8-12% compared to other PPIs 1, 2
• Avoid pantoprazole (40 mg pantoprazole equals only 9 mg omeprazole equivalents, which is inadequate) 1
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2

Treatment Duration

• 14 days is mandatory for all regimens—this improves eradication by approximately 5% compared to 7-10 day courses 1, 2

Antibiotic Selection Principles

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin where resistance develops rapidly after exposure 1, 2
• Metronidazole can be re-used with bismuth due to synergistic effects 1
• Amoxicillin and tetracycline can be re-used because resistance remains rare (<5%) 1, 2

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Was Not Used First-Line

• Bismuth quadruple therapy for 14 days (as described above) 1, 2

If Bismuth Quadruple Therapy Failed or Was Used First-Line

• Levofloxacin triple therapy for 14 days (only if no prior fluoroquinolone exposure): 1, 2
  • High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily
  • Amoxicillin 1000 mg twice daily
  • Levofloxacin 500 mg once daily

Critical caveat: Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary resistance globally). 1 Never use levofloxacin in patients with chronic lung disease or other conditions where prior fluoroquinolone exposure is likely. 1

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts

• Antibiotic susceptibility testing should guide further treatment whenever possible 1, 2, 3

Empiric Third-Line Options (if susceptibility testing unavailable)

• Rifabutin triple therapy for 14 days (if not previously used): 1, 3

  • Rifabutin 150 mg twice daily
  • Amoxicillin 1000 mg twice daily
  • High-dose PPI twice daily

• High-dose dual amoxicillin-PPI therapy for 14 days: 1, 2

  • Amoxicillin 2-3 grams daily in 3-4 split doses
  • High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily

Special Populations

Patients with Penicillin Allergy

• Bismuth quadruple therapy is the first choice (contains tetracycline, not amoxicillin) 1, 2
• Consider penicillin allergy testing to enable amoxicillin use, as most reported allergies are not true allergies 1
• If bismuth unavailable: clarithromycin + metronidazole + PPI for 14 days (only in areas with <15% clarithromycin resistance) 1

Patients with Tetracycline Contraindication

• Amoxicillin-based bismuth quadruple therapy: 1
  • Bismuth subsalicylate 262 mg four times daily
  • Metronidazole 500 mg three to four times daily
  • Amoxicillin 1000 mg twice daily
  • High-dose PPI twice daily for 14 days

Confirmation of Eradication

Test all patients for eradication success: 1, 2, 3

• Timing: At least 4 weeks after completing therapy 1, 2
• PPI discontinuation: Stop PPI at least 2 weeks before testing 1, 2
• Preferred tests: Urea breath test or validated monoclonal stool antigen test 1, 2
• Never use serology to confirm eradication—antibodies persist long after successful treatment 1

Indications for H. pylori Eradication

Test and treat H. pylori in: 4, 1

• All patients with peptic ulcer disease (active or history) 1
• First-degree relatives of patients with gastric cancer 4, 1
• Patients with previous gastric neoplasia (MALT lymphoma, adenoma, cancer) 4, 1
• Patients with severe pan-gastritis, corpus-predominant gastritis, or severe atrophy 4, 1
• Patients on chronic gastric acid inhibition for >1 year 4
• Patients with unexplained iron-deficiency anemia, idiopathic thrombocytopenic purpura, or vitamin B12 deficiency 1
• Before starting long-term NSAID therapy, especially with peptic ulcer history 1

Critical Pitfalls to Avoid

Regimens to Abandon

• Never use concomitant, sequential, or hybrid therapies—these expose patients to antibiotics that provide no therapeutic benefit and only increase global antimicrobial resistance 1, 2
• Avoid clarithromycin triple therapy without susceptibility testing when regional resistance exceeds 15% 1, 2
• Never use levofloxacin empirically as first-line therapy—this accelerates resistance and eliminates a valuable rescue option 1

Common Errors

• Using standard-dose PPI once daily (inadequate—always use twice-daily high-dose) 1, 2
• Treating for less than 14 days 1, 2
• Repeating clarithromycin or levofloxacin after previous exposure 1, 2
• Testing for eradication while patient is still on PPI 1, 2
• Using serology to confirm eradication 1

Patient Factors Affecting Success

• Smoking increases eradication failure risk (odds ratio 1.95) 1
• High BMI reduces drug concentrations at gastric mucosal level 1
• Poor compliance accounts for >10% of failures—address side effects proactively 1
• Consider adjunctive probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients) and improve compliance 1, 2