H. pylori Treatment
Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection due to rising global clarithromycin resistance and superior efficacy. 1, 2
First-Line Treatment Selection
The choice of initial therapy depends critically on local clarithromycin resistance patterns:
In Areas with High Clarithromycin Resistance (>15%)
Bismuth quadruple therapy is the mandatory first-line choice and consists of: 3, 1
- PPI (high-dose, twice daily) - esomeprazole 40 mg or rabeprazole 20 mg twice daily 4
- Bismuth subcitrate 120-140 mg 3-4 times daily 4
- Tetracycline 500 mg 4 times daily 4
- Metronidazole 500 mg 3-4 times daily 4
- Duration: 14 days 1, 5
This regimen is highly effective because bismuth resistance is virtually nonexistent, tetracycline resistance is rare in most regions, and metronidazole resistance can be overcome by adequate dosing and duration. 3, 1
In Areas with Low Clarithromycin Resistance (<15%)
Triple therapy may be considered but only if local resistance is documented to be low: 1, 2
- PPI (high-dose, twice daily) 3, 1
- Clarithromycin 500 mg twice daily 3
- Amoxicillin 1000 mg twice daily 6
- Duration: 14 days 1, 5
Alternative: Concomitant (non-bismuth quadruple) therapy consists of PPI, clarithromycin, amoxicillin, and metronidazole for 14 days. 1, 5
Critical Optimization Strategies
High-dose PPI is non-negotiable - using twice-daily dosing increases eradication rates by 6-10% compared to standard doses by maximizing gastric pH and antibiotic stability. 3, 1, 2
14-day duration is now standard - extending from 7 to 14 days improves success by approximately 5% and is strongly recommended for all regimens. 3, 1, 5
Second-Line Treatment After First-Line Failure
If Clarithromycin-Containing Triple Therapy Failed
Switch to bismuth quadruple therapy (if not used initially) for 14 days using the regimen detailed above. 3, 1, 2
Alternative: Levofloxacin-based triple therapy consists of: 3, 1, 2
- PPI twice daily
- Amoxicillin 1000 mg twice daily
- Levofloxacin 500 mg once daily (or 250 mg twice daily)
- Duration: 14 days
Critical caveat: Avoid levofloxacin in patients with chronic respiratory disease who may have prior fluoroquinolone exposure, and be aware of rising levofloxacin resistance rates. 3
If Bismuth Quadruple Therapy Failed
Levofloxacin-containing triple therapy is recommended as the second-line option in areas of high clarithromycin resistance. 3
Third-Line and Rescue Therapy
After two failed eradication attempts, antimicrobial susceptibility testing should guide treatment whenever possible. 3, 1
Rifabutin-based triple therapy can be considered as a rescue option: 1, 4
- PPI + amoxicillin + rifabutin
- Use only after multiple treatment failures due to concerns about rifabutin resistance development 4
Special Populations
Penicillin Allergy
In low clarithromycin resistance areas: Use PPI + clarithromycin + metronidazole for 14 days. 3
In high clarithromycin resistance areas: Bismuth quadruple therapy remains preferred (tetracycline can substitute for amoxicillin). 3, 4
Pediatric Patients
Avoid fluoroquinolones and tetracyclines in children, which significantly limits treatment options. 4
Verification of Eradication
Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after stopping PPI. 3, 1, 2
Never use serology to confirm eradication - antibodies persist long after successful treatment and cannot distinguish active from past infection. 3, 1, 2
Common Pitfalls to Avoid
Inadequate PPI dosing is a major cause of treatment failure - always prescribe high-dose (twice daily) PPI, preferably esomeprazole or rabeprazole rather than pantoprazole. 1, 4, 2
Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance is likely. 1
Do not use doxycycline as a substitute for tetracycline - multiple studies show significantly inferior results. 4
Clarithromycin resistance has increased dramatically from 9% in 1998 to 17.6% in 2008-2009 globally, making standard triple therapy unacceptable in many regions. 1, 2
Take medications at the start of meals to minimize gastrointestinal intolerance. 6