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 high-dose PPI twice daily, bismuth subsalicylate (262 mg four times daily) 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:

• Increasing global clarithromycin resistance now exceeding 15-20% in most regions, making traditional triple therapy unacceptably ineffective with eradication rates dropping to approximately 20% for resistant strains compared to 90% for susceptible strains 2, 3
• Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect and the fact that bacterial resistance to bismuth is extremely rare 1, 2, 3
• The WHO has identified H. pylori as one of only 12 bacterial species requiring urgent investment in new antibiotics due to high clarithromycin resistance rates 3

Critical Optimization Factors

High-dose PPI (twice daily) is mandatory and must be taken 30 minutes before meals on an empty stomach, as this increases eradication efficacy by 6-10% compared to standard dosing by reducing gastric acidity and enhancing antibiotic activity 1, 2, 3

The 14-day duration is non-negotiable as it improves eradication success by approximately 5% compared to shorter regimens 1, 2, 3

Alternative First-Line Option (When Bismuth is Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days consisting of:

• PPI twice daily
• Amoxicillin 1000 mg twice daily 4
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily 2, 3

This regimen is preferred over sequential therapy because administering all antibiotics simultaneously prevents the development of resistance during treatment 3

Second-Line Treatment After First-Line Failure

After first-line failure, choose based on what was used initially:

If bismuth quadruple therapy was NOT used first-line:

• Use bismuth quadruple therapy for 14 days 1, 2

If bismuth quadruple therapy was used first-line:

• Levofloxacin 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, 3
• Critical caveat: Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary), so avoid if the patient has had prior fluoroquinolone exposure for any indication 1, 3

Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, as resistance develops rapidly after exposure 1, 2, 3

Third-Line and Rescue Therapies

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

When susceptibility testing is unavailable:

Rifabutin triple therapy for 14 days:

• Rifabutin 150 mg twice daily
• Amoxicillin 1000 mg twice daily 4
• PPI twice daily 1, 2, 3

Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections 1

Alternative rescue option:

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

Special Populations

Penicillin Allergy:

• Bismuth quadruple therapy is the first choice as it contains tetracycline, not amoxicillin 3
• Do not assume penicillin allergy without verification—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 3

Pediatric Patients:

• Treatment should only be conducted by pediatricians in specialist centers 3
• 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 and at least 2 weeks after PPI discontinuation 1, 2, 3

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

Critical Pitfalls to Avoid

Inadequate PPI dosing is the most common error—standard once-daily dosing is inadequate; always use twice-daily high-dose PPI 1, 2, 3

Never use clarithromycin-based triple therapy empirically without knowing local resistance patterns—most regions now have clarithromycin resistance exceeding 15-20%, making this approach obsolete 2, 3

Patient compliance is crucial—more than 10% of patients are poor compliers, leading to much lower eradication rates 3

Smoking increases risk of eradication failure with an odds ratio of 1.95 for smokers versus non-smokers 3

High BMI increases risk of failure due to lower drug concentrations at the gastric mucosal level 3

Metronidazole can be re-used with bismuth because bismuth's synergistic effect overcomes in vitro resistance 3

Amoxicillin and tetracycline can be re-used because resistance to these agents remains rare 3