What is the recommended treatment for an adult patient with Peptic Ulcer Disease (PUD), potentially complicated by a history of NSAID use or Helicobacter pylori infection?

Treatment of Peptic Ulcer Disease

For adult patients with peptic ulcer disease, initiate proton pump inhibitor therapy (omeprazole 20-40 mg once daily for 4-8 weeks), test all patients for H. pylori infection and eradicate if present using 14-day clarithromycin triple therapy (in low-resistance areas), and discontinue NSAIDs immediately when possible. 1, 2

Initial Management and Acid Suppression

Start PPI therapy immediately upon diagnosis:

• Uncomplicated ulcers: Omeprazole 20 mg once daily for duodenal ulcers (4 weeks) or 40 mg once daily for gastric ulcers (4-8 weeks) 3, 4
• Bleeding ulcers with high-risk stigmata after endoscopic therapy: 80 mg IV bolus followed by 8 mg/hour continuous infusion for 72 hours, then transition to oral therapy 1, 2
• Post-bleeding maintenance: After 72 hours IV therapy, use 40 mg twice daily for days 4-14, then 40 mg once daily 1, 2

The high-dose IV regimen reduces rebleeding rates, need for surgery, and mortality compared to standard dosing 1, 5. PPIs raise gastric pH above 6, creating the environment necessary for platelet aggregation and clot stability 5.

H. pylori Testing and Eradication

Test every patient with peptic ulcer disease for H. pylori infection using noninvasive methods 1, 2:

• Preferred tests: Urea breath test or stool antigen test (more accurate than serology) 6, 7
• Important caveat: Tests have increased false-negative rates during acute bleeding episodes, so repeat testing outside the acute context if initial results are negative 1, 2

First-line eradication regimen (in areas with low clarithromycin resistance <15%):

• Standard triple therapy for 14 days 1, 2:
  • PPI (omeprazole 20 mg or equivalent) twice daily
  • Clarithromycin 500 mg twice daily
  • Amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin-allergic)

Alternative regimens when clarithromycin resistance is high:

• Sequential therapy (10 days total) 1, 2:
  • 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
• Bismuth quadruple therapy is preferred in high-resistance areas 7

Second-line therapy if first-line fails:

• Levofloxacin triple therapy for 10 days 1, 2:
  • PPI twice daily
  • Levofloxacin 500 mg once daily (or 250 mg twice daily)
  • Amoxicillin 1000 mg twice daily

Confirm eradication after treatment completion using urea breath test or stool antigen test (not serology) 1, 2. This is crucial because eradication reduces ulcer recurrence from 50-60% to 0-2%, while failure to eradicate leads to recurrence rates of 40-50% over 10 years 2, 4.

NSAID-Associated Ulcers

Discontinue all NSAIDs and aspirin immediately when peptic ulcer is diagnosed 1, 2. This single intervention heals 95% of ulcers and reduces recurrence from 40% to 9% 2, 4.

If NSAIDs must be continued for valid medical reasons:

• Test for and eradicate H. pylori if present (reduces peptic ulcer likelihood by 50% in NSAID users) 2, 7
• Switch to a selective COX-2 inhibitor (celecoxib) or lower-risk nsNSAID (ibuprofen, etodolac, or diclofenac) 1, 2
• Add PPI therapy for gastroprotection (misoprostol 600 mg/day is an alternative if tolerated) 1, 2
• Important caveat: Even with gastroprotection, risk is not eliminated—combining PPI with COX-2 inhibitor provides better protection than either alone 1

For patients with prior ulcer bleeding requiring cardiovascular prophylaxis:

• Restart low-dose aspirin as soon as cardiovascular risk outweighs bleeding risk 1
• Continue PPI therapy when using single or dual antiplatelet therapy or anticoagulants 1
• Warning: Combining aspirin with COX-2 inhibitors negates the GI-sparing effects of COX-2 selectivity, and ibuprofen may interfere with aspirin's cardiovascular benefits 1

Duration of Therapy and Follow-Up

Standard treatment duration:

• Duodenal ulcers: 4 weeks (some require additional 4 weeks) 3
• Gastric ulcers: 4-8 weeks 3
• After initial healing: Single daily-dose oral PPI for duration dictated by underlying cause 1, 2

Long-term PPI therapy is indicated only for specific populations:

• Chronic NSAID users who cannot discontinue 1, 2
• Patients with recurrent ulcers despite H. pylori eradication 2
• Pathological hypersecretory conditions (Zollinger-Ellison syndrome) 3

Hospitalization requirements:

• Most patients who undergo endoscopic hemostasis for high-risk stigmata should be hospitalized for at least 72 hours, as 60-76% of rebleeding episodes occur within this timeframe 2

Common Pitfalls and Caveats

Critical errors to avoid:

• Never use H2-receptor antagonists for acute ulcer bleeding (they are inadequate) 1
• Do not use potassium-competitive acid blockers (P-CABs like vonoprazan) as first-line therapy due to higher costs, limited availability, and less robust long-term safety data compared to PPIs 2, 5
• PPI therapy should not replace urgent endoscopy in patients with active bleeding 2
• Failure to confirm H. pylori eradication leads to recurrence rates of 40-50% over 10 years 2
• PPIs may reduce absorption of medications requiring acidic environment (consider timing and drug interactions) 2

Special considerations:

• Pre-endoscopy erythromycin improves visualization and reduces need for repeat endoscopy in bleeding ulcers 2
• Seek surgical consultation for patients in whom endoscopic therapy has failed 1
• Percutaneous embolization can be considered as an alternative to surgery where available 1