What is the appropriate treatment for a severe peptic ulcer flare‑up in an adult?

Treatment for Severe Peptic Ulcer Flare-Up

For a severe peptic ulcer flare-up, immediately initiate high-dose intravenous PPI therapy (80 mg bolus followed by 8 mg/hour continuous infusion for 72 hours), test all patients for H. pylori, and start eradication therapy with standard triple therapy (PPI + clarithromycin + amoxicillin) for 14 days beginning 72-96 hours after IV PPI initiation once oral intake resumes. 1, 2

Immediate Pharmacological Management

High-Dose PPI Therapy

• Administer an 80 mg IV PPI bolus immediately, followed by continuous infusion at 8 mg/hour for 72 hours to reduce rebleeding risk and promote healing 2
• After completing 72 hours of IV therapy, transition to oral PPI 40 mg twice daily for days 4-14 in high-risk bleeding cases, then continue once daily for 6-8 weeks total 2
• This aggressive acid suppression is critical during the acute flare-up phase, as it reduces early rebleeding and creates optimal conditions for ulcer healing 2

Pre-Endoscopy Considerations

• If endoscopy is planned, administer erythromycin 250 mg IV 30-60 minutes before the procedure to improve gastric visualization and reduce need for repeat endoscopy 2
• Do not delay PPI therapy while awaiting endoscopy, though PPIs should not replace urgent endoscopy in actively bleeding patients 2

H. pylori Testing and Eradication

Mandatory Testing

• Test ALL patients with peptic ulcer flare-ups for H. pylori before discharge using urea breath test (88-95% sensitivity, 95-100% specificity) or stool antigen test (94% sensitivity, 92% specificity) 1, 2
• Endoscopic biopsy can also detect H. pylori if endoscopy is performed 1
• Important caveat: Tests may show false-negatives during acute bleeding episodes, so repeat testing outside the acute context if initial results are negative 2

First-Line Eradication Therapy (Low Clarithromycin Resistance <15%)

Start standard triple therapy 72-96 hours after beginning IV PPI, once oral intake is tolerated, and continue for 14 days: 1, 2

• PPI standard dose (e.g., omeprazole 20-40 mg) twice daily
• Clarithromycin 500 mg twice daily
• Amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin-allergic)

This regimen achieves 77-90% eradication rates in low-resistance areas 3

Alternative Regimen (High Clarithromycin Resistance)

If clarithromycin resistance is >15-20%, use 10-day sequential therapy: 1, 3, 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

This approach achieves approximately 90% eradication even with clarithromycin resistance 1

Second-Line Therapy (If First-Line Fails)

Use 10-day levofloxacin-based triple therapy: 1, 3, 2

• PPI standard dose twice daily
• Levofloxacin 500 mg once daily (or 250 mg twice daily)
• Amoxicillin 1000 mg twice daily

Critical Management Principles

Timing Considerations

• Begin H. pylori eradication immediately when oral feeding resumes (72-96 hours after IV PPI), NOT at discharge 3
• Delaying treatment until discharge significantly reduces compliance and increases loss to follow-up 3
• Failure to eradicate H. pylori leads to 26% rebleeding rates and 40-50% recurrence over 10 years 1, 2

NSAID Management

• Discontinue ALL NSAIDs and aspirin immediately when peptic ulcer is diagnosed, as this heals 95% of ulcers and reduces recurrence from 40% to 9% 2
• If NSAIDs must be continued for valid medical reasons, switch to selective COX-2 inhibitor (celecoxib) combined with long-term PPI therapy 2
• Test for and eradicate H. pylori even in NSAID users, as eradication reduces peptic ulcer likelihood by 50% 2

Confirmation of Eradication

• Test for H. pylori eradication at least 4 weeks after completing therapy and at least 2 weeks after stopping PPI using urea breath test or stool antigen test 3, 2
• Eradication confirmation is mandatory, especially for gastric ulcers 3
• Document successful eradication to ensure treatment effectiveness 2

Common Pitfalls to Avoid

• Never use empirical antibiotics without H. pylori testing in bleeding peptic ulcers—empirical antimicrobial therapy is not recommended 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
• Avoid prolonged PPI therapy for uncomplicated duodenal ulcers after successful H. pylori eradication—healing rate exceeds 90% without additional acid suppression 3
• Do not delay endoscopy in patients with hematemesis, melena, hemodynamic instability, or severe abdominal pain—these high-risk presentations require urgent evaluation 2
• Remember that PPIs may reduce absorption of medications requiring acidic environment (e.g., certain antiretrovirals, clopidogrel) 2

Duration of PPI Therapy

• Uncomplicated duodenal ulcers: 4-8 weeks total after H. pylori eradication; no prolonged therapy needed 3, 4
• Gastric ulcers and complicated ulcers: Continue PPI until complete healing is confirmed by endoscopy, as gastric ulcers require longer acid inhibition 3
• Chronic NSAID users who cannot discontinue: Long-term PPI therapy may be necessary for secondary prophylaxis 2