Triple Therapy for H. pylori-Associated Gastric Ulcers
For gastric ulcers associated with H. pylori infection, standard triple therapy consisting of a PPI (standard dose twice daily), clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily should be administered for 14 days, but ONLY in regions where clarithromycin resistance is less than 15-20%. 1
Critical Decision Point: Local Clarithromycin Resistance Rates
The choice of first-line therapy hinges entirely on your region's clarithromycin resistance pattern, as this is the primary determinant of treatment success 1:
In Areas with LOW Clarithromycin Resistance (<15-20%)
Use standard triple therapy for 14 days: 1
- PPI (e.g., omeprazole, lansoprazole) standard dose twice daily
- Clarithromycin 500 mg twice daily
- Amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin-allergic)
The 2020 World Society of Emergency Surgery guidelines strongly recommend this regimen with moderate-quality evidence 1. The Maastricht IV consensus confirms that PPI-clarithromycin-amoxicillin and PPI-clarithromycin-metronidazole regimens are equivalent in efficacy 1.
In Areas with HIGH Clarithromycin Resistance (>15-20%)
Standard triple therapy should be abandoned entirely 1. Instead, use one of these alternatives:
Option 1 - Bismuth Quadruple Therapy (Preferred): 2, 3
- PPI twice daily
- Bismuth subcitrate
- Tetracycline
- Metronidazole
- Duration: 14 days
Option 2 - Sequential Therapy (if bismuth unavailable): 1
- Days 1-5: PPI twice daily + amoxicillin 1000 mg twice daily
- Days 6-10: PPI twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily
Option 3 - Concomitant (Non-Bismuth Quadruple) Therapy: 2
- All four drugs simultaneously for 14 days: PPI, clarithromycin, amoxicillin, and metronidazole
The American College of Gastroenterology now recommends bismuth quadruple therapy as preferred first-line treatment globally due to increasing clarithromycin resistance 2.
Optimizing Treatment Success
Duration Matters
Extend treatment to 14 days, not 7 days 1. The Maastricht IV guidelines demonstrate that extending PPI-clarithromycin-containing triple therapy from 7 to 10-14 days improves eradication success by approximately 5% 1. The 2020 WSES guidelines specifically recommend 14 days for standard triple therapy 1.
PPI Dosing is Critical
Use high-dose PPI (twice daily), not once daily 1, 2. This increases eradication efficacy by 6-10% by reducing gastric acidity and enhancing antibiotic activity 2. The evidence level for this recommendation is 1b with Grade A recommendation 1.
Timing After Acute Bleeding
Start triple therapy 72-96 hours after initiating IV PPI in bleeding gastric ulcers 1. The European Society of Gastrointestinal Endoscopy recommends starting eradication therapy immediately when oral feeding is reintroduced, not waiting until discharge, as delayed treatment significantly reduces compliance 3.
Second-Line Therapy (If First-Line Fails)
Use levofloxacin-based triple therapy for 10-14 days: 1, 2
- PPI standard dose twice daily
- Levofloxacin 500 mg once daily (or 250 mg twice daily)
- Amoxicillin 1000 mg twice daily
This is recommended with moderate-quality evidence (1B) 1. However, be aware that levofloxacin resistance rates are rising, with nearly 20% of H. pylori isolates resistant to levofloxacin in some regions 1.
Alternative second-line option: Bismuth quadruple therapy if not used first-line 1, 2.
Third-Line Therapy
After two failed eradication attempts, treatment MUST be guided by antimicrobial susceptibility testing whenever possible 1, 2, 3. The European Helicobacter Study Group gives this a high level of evidence 3.
Confirmation of Eradication
Test for eradication at least 4 weeks after completing therapy AND at least 2 weeks after stopping PPI 1, 2, 3. Use either:
- Urea breath test (sensitivity 88-95%, specificity 95-100%) 1, 3
- Monoclonal stool antigen test (sensitivity 94%, specificity 92%) 1, 3
Never use serology to confirm eradication as antibodies persist long after successful treatment 1, 2.
Acid Suppression After Eradication
For uncomplicated gastric ulcers: Continue PPI therapy after eradication treatment until complete healing is confirmed, as gastric ulcers require longer acid inhibition than duodenal ulcers 3. Healing rates exceed 90% with appropriate therapy 3.
For complicated gastric ulcers: Continue PPI until endoscopic confirmation of healing 3.
Common Pitfalls to Avoid
Critical Errors That Reduce Eradication Rates:
Using standard triple therapy in high clarithromycin resistance areas - This is the single most common mistake and results in failure rates exceeding 30% 1. Global clarithromycin resistance increased from 9% in 1998 to 17.6% in 2008-2009, and now exceeds 20% in most of Central, Western, and Southern Europe 1.
Inadequate PPI dosing - Using once-daily instead of twice-daily PPI significantly reduces efficacy 1, 2. Always prescribe high-dose (twice daily) PPI 2.
Insufficient treatment duration - Using 7 days instead of 14 days reduces eradication by approximately 5% 1.
Repeating the same antibiotics after failure - Never repeat clarithromycin or levofloxacin if previously used, as resistance is likely 2.
Delaying treatment until discharge in bleeding ulcers - This significantly reduces compliance and increases loss to follow-up 3.
Not confirming eradication - Eradication confirmation is mandatory for gastric ulcers 3.
Testing too early after treatment - Testing before 4 weeks post-treatment or within 2 weeks of PPI use yields false results 1, 2, 3.
FDA-Approved Dosing for H. pylori
Triple therapy (FDA-approved): 4
- Amoxicillin 1 gram twice daily (every 12 hours)
- Clarithromycin 500 mg twice daily
- Lansoprazole 30 mg twice daily
- Duration: 14 days
Take all medications at the start of meals to minimize gastrointestinal intolerance 4.