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

Helicobacter 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 proton pump inhibitor (PPI) twice daily, bismuth subsalicylate 262 mg or bismuth subcitrate 120 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:

• Clarithromycin resistance now exceeds 15% in most regions globally, making traditional triple therapy unacceptably ineffective with eradication rates dropping from 90% to approximately 20% when resistance is present 1, 2
• Bismuth quadruple therapy achieves 80-90% eradication rates even against strains resistant to both clarithromycin and metronidazole due to bismuth's synergistic effect 1, 2
• No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare 1

Alternative First-Line Option When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily 1, 2

• This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment 1
• Only consider this in areas where bismuth is truly unavailable 1

When Triple Therapy May Be Considered

In areas with documented clarithromycin resistance <15%: PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days 1, 2

Critical caveat: Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1

Optimizing Treatment Success

PPI Dosing (Mandatory)

• Use high-dose PPI twice daily (not standard once-daily dosing), which increases eradication efficacy by 6-10% 1, 2, 3
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% compared to other PPIs 1
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1

Treatment Duration

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

Adjunctive Therapy

• Consider probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients), though evidence for improving eradication rates is limited 1, 2

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Failed First

Levofloxacin-based triple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 2

Critical caveat: Levofloxacin resistance rates range from 11-30% (primary) and 19-30% (secondary), so do not use if patient has prior fluoroquinolone exposure 1

If Clarithromycin-Based Therapy Failed First

Bismuth quadruple therapy for 14 days (if not previously used) 1, 2

Key Principle

Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts

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

If susceptibility testing is unavailable:

1. Rifabutin-based 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 1
   • Reserve for patients who have failed previous eradication attempts 1

2. High-dose dual amoxicillin-PPI therapy for 14 days: Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily 1

   • Alternative when other options have been exhausted 1

Special Populations

Penicillin Allergy

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

Pediatric Patients

• Treatment should only be conducted by pediatricians in specialist centers 1
• Fluoroquinolones and tetracyclines should not be used in children 2

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test:

• At least 4 weeks after completion of therapy 1, 2, 3
• At least 2 weeks after PPI discontinuation 1, 2, 3

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

Critical Pitfalls to Avoid

• Inadequate PPI dosing (once daily or standard dose) significantly reduces treatment efficacy 2, 3
• Repeating clarithromycin if patient has prior macrolide exposure for any indication—cross-resistance is universal within the macrolide family 1
• Using levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates 1
• Assuming penicillin allergy without verification—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 1

Patient Factors Affecting Success

• Smoking increases risk of eradication failure (odds ratio 1.95) 1
• High BMI increases risk of failure due to lower drug concentrations at the gastric mucosal level 1
• Poor compliance (>10% of patients) leads to much lower eradication rates—address adherence proactively 1