Treatment of Helicobacter pylori Infection
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, metronidazole, and tetracycline, achieving 80-90% eradication rates even against metronidazole-resistant strains. 1
First-Line Treatment Selection
The choice of first-line therapy depends critically on local clarithromycin resistance patterns, which now exceed 15-20% in most regions of North America and Europe 1:
In Areas with High Clarithromycin Resistance (≥15-20%)
Bismuth quadruple therapy for 14 days is the recommended first-line regimen 2, 1
- Components: PPI twice daily + bismuth subsalicylate + metronidazole + tetracycline 1
- This regimen uses antibiotics from the WHO "Access group" rather than "Watch group," making it preferable from an antimicrobial stewardship perspective 1
- Bismuth has the critical advantage of extremely rare bacterial resistance, maintaining efficacy even against metronidazole-resistant strains 1, 3
Alternative when bismuth is unavailable: Concomitant non-bismuth quadruple therapy for 14 days 1
In Areas with Low Clarithromycin Resistance (<15%)
- Triple therapy for 14 days may be considered 2, 1
- Components: PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily 1
- However, standard triple therapy should be abandoned when regional clarithromycin resistance exceeds 15-20%, as eradication rates drop to approximately 20% with resistant strains compared to 90% with susceptible strains 1
Critical Optimization Strategies
PPI Dosing
- Always use high-dose PPI twice daily (e.g., esomeprazole or rabeprazole 40 mg twice daily) 2, 1, 3
- High-dose PPI increases eradication efficacy by 6-10% compared to standard doses by reducing gastric acidity and enhancing antibiotic activity 2, 1, 4
- Standard-dose PPI once daily is inadequate and significantly reduces treatment efficacy 1, 3
Treatment Duration
- 14-day duration is strongly preferred over 7-10 days for all regimens 1, 3, 4
- Extending treatment from 7 to 14 days improves eradication success by approximately 5% 2, 1, 4
FDA-Approved Dosing for H. pylori
For triple therapy with clarithromycin and lansoprazole: 1 gram amoxicillin + 500 mg clarithromycin + 30 mg lansoprazole, all given twice daily for 14 days 5
Second-Line Treatment After First-Line Failure
After failure of first-line therapy, select from these options based on prior antibiotic exposure 1, 3:
Bismuth quadruple therapy for 14 days (if not previously used) 2, 3, 4
Levofloxacin triple therapy for 14 days 2, 3, 4
- Components: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 4
- Critical caveat: Rising levofloxacin resistance rates (11-30% primary, 19-30% secondary) limit this option 1
- Do not use levofloxacin empirically as first-line therapy 1
- The FDA recommends fluoroquinolones be used as a last choice due to risk of serious side effects 1
Third-Line and Rescue Therapy
After two failed eradication attempts, antimicrobial susceptibility testing should guide further treatment whenever possible 2, 1, 3
Rifabutin triple therapy for 14 days is highly effective for persistent infection 1, 3
High-dose dual amoxicillin-PPI therapy is an alternative rescue option 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 2, 1, 3, 4
- Serology should never be used to confirm eradication as antibodies persist long after successful treatment 1, 3, 4
Critical Pitfalls to Avoid
Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1
Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as cross-resistance is universal within antibiotic families 1, 3
Never use standard-dose PPI once daily—this is the most common cause of treatment failure 1, 3
Never use PPI-clarithromycin triple therapy without prior susceptibility testing when regional clarithromycin resistance exceeds 15-20% 2, 1
Patient Factors Affecting Success
Smoking increases risk of eradication failure with an odds ratio of 1.95 1
High BMI, especially obesity, increases failure risk due to lower drug concentrations at the gastric mucosal level 1
Confirm patients are taking PPI correctly (at the start of a meal per FDA labeling) to maximize absorption and activation 3, 5