What is the best practice for treating a patient with a confirmed diagnosis of H pylori (Helicobacter pylori) infection?

Best Practice for H. pylori Treatment

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline, achieving 80-90% eradication rates even in areas with high antibiotic resistance. 1

First-Line Treatment Regimen

Bismuth quadruple therapy should be prescribed as follows:

• High-dose PPI: Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs as they increase cure rates by 8-12%) 1, 2
• Bismuth subsalicylate: 262 mg (2 tablets) four times daily 2
• Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline: 500 mg four times daily 2
• Duration: 14 days mandatory (improves eradication by approximately 5% compared to shorter regimens) 1

Critical administration details:

• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 2
• Take bismuth and antibiotics with meals to minimize gastrointestinal side effects 1

Why bismuth quadruple therapy is superior:

• Not affected by clarithromycin resistance, which now exceeds 15-20% in most of North America and Europe 1, 2
• No bacterial resistance to bismuth has been described 2
• Bismuth's synergistic effect overcomes metronidazole resistance even when present 2
• Tetracycline resistance remains rare (<5%) 1, 2

Alternative First-Line Option (When Bismuth Unavailable)

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

• Esomeprazole or rabeprazole 40 mg twice daily 2
• Amoxicillin 1000 mg twice daily 2
• Clarithromycin 500 mg twice daily 2
• Metronidazole 500 mg twice daily 2

This regimen should ONLY be used when:

• Bismuth is unavailable 2
• Local clarithromycin resistance is documented below 15% 1, 2
• Patient has no prior macrolide exposure 1

Critical Pitfalls to Avoid

Do NOT use the following approaches:

• Standard triple therapy (PPI + clarithromycin + amoxicillin) as empiric first-line therapy - achieves only 70% eradication in most regions due to clarithromycin resistance exceeding 15-20% 1, 2
• Concomitant, sequential, or hybrid therapies - these include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1, 2
• 7-10 day treatment durations - 14 days is mandatory for optimal outcomes 1
• Standard-dose PPI once daily - high-dose twice-daily dosing is required 1, 2
• Pantoprazole - significantly lower potency than esomeprazole or rabeprazole 2

Antibiotic Selection Based on Prior Exposure

Before prescribing, obtain thorough antibiotic history: 1

• If prior clarithromycin exposure (for any indication): Avoid all clarithromycin-containing regimens - resistance is universal within macrolide family 1
• If prior fluoroquinolone exposure: Avoid levofloxacin-based regimens - cross-resistance exists 1, 2
• Safe to re-use: Amoxicillin, tetracycline, rifabutin (resistance rates <5%) 1, 2
• Can re-use with bismuth: Metronidazole (bismuth overcomes resistance) 1, 2

Second-Line Treatment After First-Line Failure

If bismuth quadruple therapy fails, use levofloxacin triple therapy (only if no prior fluoroquinolone exposure): 1, 2

• Esomeprazole or rabeprazole 40 mg twice daily 2
• Amoxicillin 1000 mg twice daily 2
• Levofloxacin 500 mg once daily 1, 2
• Duration: 14 days 1, 2

If clarithromycin-based therapy fails, use bismuth quadruple therapy as described above. 1, 2

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, obtain antibiotic susceptibility testing to guide further treatment. 1

Susceptibility testing options: 1

• Culture from gastric biopsies (available from Mayo Clinic, ARUP, Labcorp, Quest Diagnostics) 1
• Molecular testing using next-generation sequencing from stool or gastric biopsies (American Molecular Laboratories) 1
• Reflex stool testing (automatic susceptibility testing if H. pylori positive) 1

Third-line options when susceptibility testing unavailable:

• Rifabutin triple therapy for 14 days: 1, 2

  • Rifabutin 150 mg twice daily 2
  • Amoxicillin 1000 mg twice daily 2
  • Esomeprazole or rabeprazole 40 mg twice daily 2
  • Rifabutin resistance is rare 1, 2

• High-dose dual amoxicillin-PPI therapy for 14 days: 1, 2

  • Amoxicillin 2-3 grams daily in 3-4 split doses 2
  • Esomeprazole or rabeprazole 40 mg twice daily 2

Special Populations

Penicillin allergy:

• Bismuth quadruple therapy is first choice (contains tetracycline, not amoxicillin) 2
• Consider penicillin allergy testing to delist the allergy and enable amoxicillin use 1, 2
• Most patients labeled as penicillin allergic are found not to have true allergy 2

Pregnant or breastfeeding patients:

• Defer treatment until after pregnancy/breastfeeding when possible 3
• If treatment necessary, amoxicillin-based regimens are safest 3

Confirmation of Eradication

Test for eradication success at least 4 weeks after completing therapy using: 1, 2

• Urea breath test (sensitivity 94.7-97%, specificity 95-95.7%) 4
• Laboratory-based monoclonal stool antigen test (sensitivity 93%, specificity 93%) 4

Critical testing requirements:

• Discontinue PPI at least 2 weeks before testing 2, 4
• Discontinue antibiotics and bismuth at least 4 weeks before testing 4
• Never use serology to confirm eradication - antibodies persist long after successful treatment 2, 4

Optimizing Treatment Success

Factors that improve eradication rates:

• High-dose PPI twice daily increases efficacy by 6-12% compared to standard dosing 1, 2
• 14-day duration improves success by approximately 5% compared to 7-10 days 1
• Patient adherence - explain rationale, dosing instructions, expected side effects, and importance of completing full course 1
• Adequate acid suppression - use esomeprazole or rabeprazole 40 mg twice daily 1, 2

Patient factors associated with treatment failure:

• Smoking (odds ratio 1.95 for failure) 2
• High BMI (lower drug concentrations at gastric mucosal level) 2
• Poor compliance (>10% of patients) 2

Antimicrobial Stewardship Principles

The approach to H. pylori treatment must shift from trial-and-error to evidence-based antimicrobial stewardship: 1

• Target ≥95% cure rate with susceptible infections 1
• Use susceptibility-based therapy when possible 1
• Exclude antibiotics where preexisting resistance is likely based on history 1
• Compile and share local treatment outcome data 1
• Avoid empiric use of clarithromycin, metronidazole, or fluoroquinolone triple therapies due to high resistance rates 1