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

H. pylori Treatment

First-Line Treatment Recommendation

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a 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 recommendation is based on:

• Eradication rates of 80-90% even in areas with high clarithromycin and metronidazole resistance 1, 2
• No bacterial resistance to bismuth has been described, making this regimen reliable across all geographic regions 1, 2
• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, rendering traditional triple therapy inadequate with only 70% eradication rates 1, 3

Critical Optimization Factors

PPI Selection and Dosing

• Use high-dose PPI twice daily (not standard once-daily dosing) to increase cure rates by 6-12% 1, 2, 3
• Esomeprazole or rabeprazole 40 mg twice daily are preferred over other PPIs as they increase cure rates by an additional 8-12% 1
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1

Treatment Duration

• 14 days is mandatory for all regimens, improving eradication by approximately 5% compared to 7-10 day courses 1, 2, 3, 4

Alternative First-Line Option (When Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days: 1, 2

• PPI twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily

This regimen should only be used when bismuth is truly unavailable, as it includes clarithromycin which contributes to global antibiotic resistance 1

Triple Therapy: Severely Restricted Use

PPI-clarithromycin-amoxicillin triple therapy should be abandoned in most clinical settings 1, 3

Only consider in areas with documented clarithromycin resistance <15%, which is now rare in North America and Europe 1, 2, 3

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Failed First

Levofloxacin-based triple therapy for 14 days (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)

Critical caveat: Levofloxacin resistance rates are 11-30% (primary) and 19-30% (secondary), so avoid if patient has had any prior fluoroquinolone exposure 1

If Clarithromycin-Containing Therapy Failed First

Use bismuth quadruple therapy for 14 days as described above 1, 2

Never repeat clarithromycin after initial failure—resistance develops rapidly and cross-resistance is universal within the macrolide family 1, 2

Third-Line and Rescue Therapies

After Two Failed Attempts

Antibiotic susceptibility testing should guide further treatment whenever possible 1, 2, 3, 5, 4

Rifabutin-Based Triple Therapy (Rescue Option)

For 14 days: 1, 2

• Rifabutin 150 mg twice daily
• Amoxicillin 1000 mg twice daily
• PPI twice daily

Rifabutin resistance is extremely rare, making this effective after multiple failures 1

High-Dose Dual Therapy (Last Resort)

For 14 days: 1

• Amoxicillin 2-3 grams daily in 3-4 divided doses
• High-dose PPI twice daily

Special Populations

Penicillin Allergy

Bismuth quadruple therapy is the first choice as it contains tetracycline, not amoxicillin 1, 2

Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains rare (<5%) 1

Pediatric Patients

• Avoid fluoroquinolones and tetracyclines in children 2
• First-line options: PPI + amoxicillin + clarithromycin, or PPI + amoxicillin + metronidazole 1
• Treatment should only be conducted by pediatricians in specialist centers 1

Pregnancy and Breastfeeding

Amoxicillin is FDA pregnancy category B and compatible with breastfeeding 6

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test: 1, 2, 3

• At least 4 weeks after completion of therapy
• At least 2 weeks after PPI discontinuation

Never use serology to confirm eradication—antibodies persist long after successful treatment 1, 2

Managing Side Effects

• Diarrhea occurs in 21-41% of patients during the first week due to gut microbiota disruption 1
• Consider adjunctive probiotics to reduce diarrhea risk and improve compliance, though evidence for increased eradication rates is limited 1, 2, 3

Critical Pitfalls to Avoid

• Never use standard-dose PPI once daily—always twice-daily high-dose 1, 2, 3
• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin 1, 2
• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance 1
• Avoid concomitant, sequential, or hybrid therapies as they include unnecessary antibiotics contributing to global resistance without therapeutic benefit 1
• Do not use fluoroquinolones as first-line therapy due to rapidly rising resistance rates and FDA warnings about serious side effects 1

Patient Factors Affecting Success

• Smoking increases failure risk (odds ratio 1.95) 1
• High BMI/obesity increases failure due to lower drug concentrations at gastric mucosal level 1
• Poor compliance accounts for >10% of failures—emphasize importance of completing full 14-day course 1