What is the recommended treatment and duration for Helicobacter pylori (H. pylori) infection?

Treatment and Duration for H. pylori Infection

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance. 1 This regimen is superior because:

• No bacterial resistance to bismuth has been described 3, 1
• Tetracycline resistance remains rare (1-5%) 1
• Bismuth's synergistic effect overcomes metronidazole resistance even when present in vitro 1

Specific Dosing for Bismuth Quadruple Therapy

• PPI (esomeprazole or rabeprazole preferred): 40 mg twice daily, taken 30 minutes before meals 1
• Bismuth subsalicylate: 262 mg (2 tablets) four times daily 1
• Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline: 500 mg four times daily 1
• Duration: 14 days (mandatory—not 10 days) 1, 2

Alternative First-Line Option When Bismuth Unavailable

• Concomitant non-bismuth quadruple therapy: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days 1, 4
• This regimen should only be used when bismuth is truly unavailable, as it contributes more to antibiotic resistance 1

Critical Optimization Factors

• High-dose PPI twice daily is mandatory—standard once-daily dosing reduces eradication rates by 6-10% 1, 5
• 14-day duration is superior to 7-10 days, improving eradication by approximately 5% 3, 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily increase cure rates by an additional 8-12% compared to other PPIs 1

Why Traditional Triple Therapy Should Be Avoided

• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe 1, 4
• When H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to approximately 20% 1
• The WHO has identified H. pylori as one of only 12 bacterial species requiring urgent investment due to high clarithromycin resistance 1

Second-Line Treatment After First-Line Failure

After bismuth quadruple therapy failure, levofloxacin triple therapy for 14 days is the preferred second-line option (if no prior fluoroquinolone exposure): 1, 2

• PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 4
• Critical caveat: Levofloxacin resistance rates are 11-30% (primary) and 19-30% (secondary), so avoid if previously used 1

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible. 3, 1, 2

If susceptibility testing unavailable:

• Rifabutin triple therapy for 14 days: Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily 1, 2
• Rifabutin resistance is extremely rare, making this highly effective for rescue therapy 1
• High-dose dual amoxicillin-PPI therapy: Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily for 14 days 1

Verification of Eradication

• Test at least 4 weeks after completion of therapy using urea breath test or monoclonal stool antigen test 3, 1, 5
• Discontinue PPI at least 2 weeks before testing to avoid false-negative results 1, 5
• Never use serology to confirm eradication—antibodies persist long after successful treatment 1, 5

Special Clinical Scenarios

Penicillin Allergy

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1
• Consider penicillin allergy testing to enable amoxicillin use, as true allergy is often overreported 1

Bleeding Peptic Ulcer

• Start H. pylori eradication treatment immediately when oral feeding is reintroduced 3, 1
• For uncomplicated duodenal ulcer, prolonged PPI after eradication is not needed 3
• For gastric ulcer or complicated duodenal ulcer, continue PPI and confirm healing endoscopically 3

Before Starting NSAIDs

• H. pylori eradication is mandatory in patients with peptic ulcer history before starting NSAID therapy 1

Common Pitfalls to Avoid

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin—resistance develops rapidly after exposure 1, 2
• Never use standard-dose PPI once daily—this is the most common cause of preventable treatment failure 1, 5
• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance 1
• Never use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance and FDA warnings about serious side effects 1
• Never use concomitant, sequential, or hybrid therapies when bismuth is available—they include unnecessary antibiotics that contribute to global resistance 1

Patient Factors Affecting Success

• Smoking increases eradication failure risk (odds ratio 1.95) 1
• High BMI reduces drug concentrations at the gastric mucosal level 1
• Poor compliance accounts for >10% of failures—address this proactively 1
• Diarrhea occurs in 21-41% of patients during the first week; consider adjunctive probiotics to improve compliance 1