Amoxicillin Dosing for Helicobacter pylori Eradication
Recommended Amoxicillin Dose in First-Line Regimens
Amoxicillin 1000 mg (1 gram) twice daily is the standard dose for all first-line H. pylori eradication regimens in adults, administered as part of a 14-day course. 1, 2, 3
- Plain amoxicillin is required; amoxicillin-clavulanate adds no benefit and increases adverse effects. 2
- Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance. 3
- The 14-day duration is mandatory, as extending therapy from 7 to 14 days improves eradication by approximately 5%. 1, 2, 4
First-Line Regimen Selection
Bismuth Quadruple Therapy (Preferred First-Line)
Bismuth quadruple therapy for 14 days is the recommended first-line treatment in most clinical scenarios, achieving 80–90% eradication rates even in regions with high clarithromycin and metronidazole resistance (>15%). 1, 2
Regimen components:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1, 2, 4
- Bismuth subsalicylate 262 mg (2 tablets) four times daily 1, 2
- Metronidazole 500 mg three to four times daily 1, 5
- Tetracycline 500 mg four times daily 1, 2
- Duration: 14 days 1, 2, 4
Note: This regimen does not contain amoxicillin but is the preferred empiric first-line option due to superior efficacy and lack of dependence on clarithromycin susceptibility. 1, 2
Concomitant (Non-Bismuth) Quadruple Therapy (Alternative First-Line)
When bismuth is unavailable, concomitant quadruple therapy for 14 days may be used, but only in regions with documented clarithromycin resistance <15%. 1, 2
Regimen components:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 2, 4
- Amoxicillin 1000 mg twice daily 1, 2
- Clarithromycin 500 mg twice daily 1, 2
- Metronidazole 500 mg twice daily 1, 5
- Duration: 14 days 1, 2, 4
Clarithromycin Triple Therapy (Restricted Use)
Standard triple therapy (PPI + clarithromycin + amoxicillin) should only be used in areas with documented clarithromycin resistance <15% and achieves only ~70% eradication in most regions. 1, 2
Regimen components:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 2, 4
- Amoxicillin 1000 mg twice daily 1, 2, 3
- Clarithromycin 500 mg twice daily 1, 2
- Duration: 14 days 1, 2, 4
Critical caveat: Do not use this regimen empirically in North America or most of Europe, where clarithromycin resistance exceeds 15–20%. 1, 2
Optimizing Amoxicillin Efficacy
Dosing Frequency Considerations
Although standard regimens use amoxicillin 1000 mg twice daily, evidence suggests that more frequent dosing (three or four times daily) may improve eradication rates because amoxicillin's bactericidal effect depends on time-above-MIC. 6
- In a study of 187 patients with clarithromycin-sensitive strains, eradication rates were 77.8% with twice-daily amoxicillin, 93.5% with three-times-daily, and 91.9% with four-times-daily dosing. 6
- However, current guidelines uniformly recommend 1000 mg twice daily for practical compliance reasons. 1, 2, 3
PPI Optimization
High-dose PPI (esomeprazole or rabeprazole 40 mg twice daily) increases cure rates by 8–12% compared to standard-dose PPIs, because higher intragastric pH enhances amoxicillin stability and activity. 1, 2, 4
- PPIs must be taken 30 minutes before meals on an empty stomach, without concomitant antacids. 1, 2, 4
- Avoid pantoprazole; 40 mg pantoprazole provides acid suppression equivalent to only 9 mg omeprazole. 2, 4
Second-Line Regimens After First-Line Failure
Levofloxacin Triple Therapy (Second-Line)
After failure of clarithromycin-based or bismuth quadruple therapy, levofloxacin triple therapy for 14 days is recommended, provided the patient has no prior fluoroquinolone exposure. 1, 2
Regimen components:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1, 2
- Amoxicillin 1000 mg twice daily 1, 2
- Levofloxacin 500 mg once daily 1, 2
- Duration: 14 days 1, 2
Critical caveat: Never use levofloxacin in patients with prior fluoroquinolone exposure for any indication, as cross-resistance is universal. 1, 2
High-Dose Dual Therapy (Rescue Option)
High-dose dual therapy is an alternative rescue option after multiple failures, consisting of amoxicillin 2–3 grams daily divided into 3–4 doses plus high-dose PPI twice daily for 14 days. 1, 2
Regimen components:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1, 2
- Amoxicillin 2000–3000 mg daily in 3–4 divided doses 1, 2
- Duration: 14 days 1, 2
Pediatric Dosing
Children ≥3 Months and Weight <40 kg
For mild to moderate infections: Amoxicillin 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours 3
For severe infections or lower respiratory tract infections: Amoxicillin 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours 3
For H. pylori eradication in children: First-line options include PPI + amoxicillin + clarithromycin, PPI + amoxicillin + metronidazole, or bismuth + amoxicillin + metronidazole 2
Critical caveat: Treatment of H. pylori in pediatric patients should only be conducted by pediatricians in specialist centers. 2
Management of Penicillin Allergy
In patients with documented penicillin allergy, bismuth quadruple therapy (which contains tetracycline, not amoxicillin) is the first-choice regimen. 1, 2, 7
After first-line failure in penicillin-allergic patients, consider formal penicillin allergy testing, as most reported allergies are not true allergies; this allows amoxicillin use in subsequent regimens. 1, 2, 7
If penicillin allergy is confirmed, second-line options include:
- Levofloxacin triple therapy (PPI + metronidazole + levofloxacin) for 14 days 2
- After two failures, antibiotic susceptibility testing should guide further treatment 1, 2, 7
Critical Pitfalls to Avoid
- Never use amoxicillin-clavulanate; plain amoxicillin is required. 2
- Never use once-daily PPI dosing; twice-daily high-dose PPI is mandatory. 1, 2, 4
- Never shorten therapy below 14 days; this reduces eradication success by ~5%. 1, 2, 4
- Never repeat amoxicillin-containing regimens without changing the other antibiotics; resistance patterns must be considered. 1, 2
- Never use clarithromycin-based triple therapy empirically in regions with clarithromycin resistance >15%. 1, 2
- Never assume penicillin allergy without verification; consider allergy testing to enable amoxicillin use. 1, 2, 7
Confirmation of Eradication
Test-of-cure is mandatory using urea breath test or monoclonal stool antigen test ≥4 weeks after completing therapy. 1, 2
Discontinue PPI ≥2 weeks (preferably 7–14 days) before testing to avoid false-negative results. 1, 2
Never use serology for test-of-cure; antibodies persist long after successful eradication. 1, 2