Initial Treatment for Peptic Ulcer Disease
Start proton pump inhibitor (PPI) therapy immediately at standard doses (omeprazole 20-40 mg once daily or equivalent) for 6-8 weeks, test all patients for H. pylori infection, and initiate eradication therapy with 14-day standard triple therapy (PPI + clarithromycin 500 mg + amoxicillin 1000 mg, all twice daily) if positive. 1, 2
Immediate Pharmacological Management
PPI Therapy
- Begin PPI therapy as soon as peptic ulcer disease is diagnosed, even before endoscopy if clinically indicated 1, 2
- Standard dosing: omeprazole 20-40 mg once daily (or equivalent PPI) for 6-8 weeks to allow complete mucosal healing 2, 3
- PPIs heal 80-100% of peptic ulcers within 4 weeks; gastric ulcers larger than 2 cm may require 8 weeks of treatment 3
Special Considerations for Bleeding Ulcers
- For bleeding peptic ulcers with high-risk stigmata after endoscopic hemostasis: administer 80 mg PPI bolus followed by 8 mg/hour continuous infusion for 72 hours 1, 2, 4
- This high-dose regimen significantly reduces rebleeding (5.9% vs 10.3%, p=0.03) and need for endoscopic retreatment 1
- Pre-endoscopy erythromycin improves gastric visualization and reduces need for repeat endoscopy 1, 2, 4
H. pylori Testing and Eradication
Testing Strategy
- Test all patients with peptic ulcer disease for H. pylori infection using non-invasive methods 1, 2
- Preferred tests: urea breath test (sensitivity 88-95%, specificity 95-100%) or stool antigen testing (sensitivity 94%, specificity 92%) 1
- For bleeding ulcers, H. pylori testing can be performed on endoscopic tissue biopsy 1
First-Line Eradication Therapy
Standard triple therapy for 14 days (in areas with low clarithromycin resistance) 1, 2:
- PPI standard dose twice daily
- Clarithromycin 500 mg twice daily
- Amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin allergic)
Start triple therapy after 72-96 hours of intravenous PPI administration in bleeding ulcers 1
Alternative Regimens for High Clarithromycin Resistance
Sequential therapy for 10 days 1, 2:
- Days 1-5: PPI standard dose twice daily + amoxicillin 1000 mg twice daily
- Days 6-10: PPI standard dose twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily
Second-Line Therapy if First-Line Fails
Levofloxacin-amoxicillin triple therapy for 10 days 1, 2:
- PPI standard dose twice daily
- Levofloxacin 500 mg once daily (or 250 mg twice daily)
- Amoxicillin 1000 mg twice daily
NSAID-Related Ulcer Management
- Discontinue NSAID therapy when possible—this heals 95% of ulcers and reduces recurrence from 40% to 9% 3, 5
- If NSAID continuation is necessary: maintain long-term PPI therapy 1, 2
- Consider switching to a less gastrotoxic NSAID (e.g., from ketorolac to ibuprofen or celecoxib) 3, 5
- Eradicating H. pylori in NSAID users reduces peptic ulcer likelihood by 50% 5
Duration and Follow-Up
Standard Ulcer Treatment
- Continue oral PPI therapy for 6-8 weeks after initial treatment 1, 2, 3
- Long-term PPI therapy is NOT recommended unless the patient has ongoing NSAID use or recurrent ulcers despite H. pylori eradication 1, 2
Post-Eradication
- H. pylori eradication decreases ulcer recurrence from 50-60% to 0-2% 3
- Failure to test for and eradicate H. pylori leads to recurrence rates of 40-50% over 10 years 2, 4
Critical Pitfalls to Avoid
- Never rely solely on PPI therapy without endoscopic intervention in patients with active bleeding—urgent endoscopy remains first-line treatment 1, 2, 4
- Do not discontinue PPI therapy before 6-8 weeks, as this may not allow adequate mucosal healing 4
- Patients with clarithromycin-resistant H. pylori should not receive any regimen containing clarithromycin as the sole antimicrobial agent 6
- H. pylori-negative ulcers are more aggressive with higher recurrence rates and increased bleeding/perforation risk—consider long-term PPI therapy in these patients 7
- The combination of H. pylori infection and NSAID use synergistically increases bleeding ulcer risk more than sixfold 5