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

H. pylori Treatment

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

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it the preferred initial approach. 1 This regimen consists of:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, taken 30 minutes before meals) 1
• Bismuth subsalicylate 262 mg (or bismuth subcitrate 120 mg) 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 1

The superiority of bismuth quadruple therapy stems from the fact that bacterial resistance to bismuth is extremely rare, and the synergistic effect of bismuth overcomes metronidazole resistance even when present. 1

Alternative First-Line Option When Bismuth Unavailable

Concomitant non-bismuth quadruple therapy is the recommended alternative when bismuth is not available, consisting of: 1

• PPI twice daily 1
• Amoxicillin 1000 mg twice daily 1, 2
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1
• Duration: 14 days 1

This regimen should only be used when bismuth quadruple therapy cannot be administered, as clarithromycin resistance now exceeds 15% in most regions, making traditional triple therapy unacceptably ineffective. 1

Critical Optimization Factors

High-dose PPI dosing is mandatory and significantly impacts success rates. 1 Key optimization strategies include:

• Use esomeprazole or rabeprazole 40 mg twice daily, which increases cure rates by 8-12% compared to other PPIs 1
• Standard once-daily PPI dosing is inadequate—always use twice-daily dosing to increase efficacy by 6-10% 1
• Take PPI 30 minutes before meals on an empty stomach without concomitant antacids 1
• 14-day duration is superior to shorter regimens, improving eradication by approximately 5% compared to 7-10 day courses 1

Second-Line Treatment After First-Line Failure

After first-line treatment failure, select a regimen based on antibiotics not previously used. 3

If bismuth quadruple therapy was not used first-line, use it as second-line therapy for 14 days. 3

If bismuth quadruple therapy was used first-line, levofloxacin triple therapy is recommended (only if no prior fluoroquinolone exposure): 3

• PPI twice daily 3
• Amoxicillin 1000 mg twice daily 3
• Levofloxacin 500 mg once daily or 250 mg twice daily 3
• Duration: 14 days 3

Critical caveat: Rising levofloxacin resistance rates (11-30% primary, 19-30% secondary) make this less reliable, and fluoroquinolones should never be used empirically as first-line therapy. 1

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient compliance, antibiotic susceptibility testing should guide further treatment whenever possible. 3

When susceptibility testing is unavailable, rescue options include:

Rifabutin triple therapy for 14 days: 3

• Rifabutin 150 mg twice daily 3
• Amoxicillin 1000 mg twice daily 3, 2
• High-dose PPI twice daily 3

Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections. 3

High-dose dual amoxicillin-PPI therapy is an alternative rescue option: 3

• Amoxicillin 2-3 grams daily in 3-4 divided doses 3
• High-dose PPI twice daily 3
• Duration: 14 days 3

Special Populations

For patients with penicillin allergy, bismuth quadruple therapy is the first choice since it contains tetracycline rather than amoxicillin. 1 However, consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains extremely rare (<5%). 1

In pediatric patients, fluoroquinolones and tetracyclines should not be used, limiting treatment options. 1

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. 3

Never use serology to confirm eradication—antibodies may persist long after successful treatment. 3

Common Pitfalls to Avoid

Inadequate PPI dosing is the most common error—standard once-daily dosing significantly reduces treatment efficacy. 1 Always use high-dose (twice daily) PPI. 1

Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance develops rapidly after exposure. 3

Clarithromycin resistance is increasing globally (from 9% in 1998 to 17.6% in 2008-2009), making traditional triple therapy achieve only 70% eradication rates in many regions—well below the 80% minimum target. 1 When H. pylori strains are clarithromycin-resistant, eradication rates drop to approximately 20% compared to 90% with susceptible strains. 1

Patient compliance is crucial—more than 10% of patients are poor compliers, leading to much lower eradication rates. 1 Address compliance issues proactively.

Smoking increases risk of treatment failure with an odds ratio of 1.95 for eradication failure among smokers versus non-smokers. 1

High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level. 1