How should a peptic ulcer be managed, including testing for Helicobacter pylori and appropriate therapy for H. pylori‑positive, H. pylori‑negative, and NSAID‑induced ulcers?

Management of Peptic Ulcer Disease

All patients with peptic ulcer disease must be tested for Helicobacter pylori and receive 14-day bismuth quadruple therapy or concomitant quadruple therapy as first-line eradication treatment, combined with high-dose PPI therapy for 4–6 weeks, followed by mandatory confirmation of eradication and endoscopic verification of healing for gastric ulcers. 1

Initial Diagnostic Testing

• Perform upper endoscopy with multiple biopsies from the ulcer margin and base for all gastric ulcers to exclude malignancy, and obtain at least two biopsies each from the antrum and body for H. pylori testing using both histology and rapid urease test. 1

• For duodenal ulcers in patients under 60 years without alarm symptoms, use non-invasive testing with urea breath test (88–95% sensitivity, 95–100% specificity) or monoclonal stool antigen test (94% sensitivity, 92% specificity). 2, 1

• In actively bleeding ulcers, biopsy-based H. pylori tests have a 25–55% false-negative rate; repeat testing after hemostasis is mandatory. 1

• Never use serology to confirm eradication because antibodies persist for months to years after successful therapy. 1

First-Line Eradication Therapy for H. pylori-Positive Ulcers

• Initiate 14-day bismuth quadruple therapy immediately when oral intake is tolerated: esomeprazole or rabeprazole 40 mg twice daily, bismuth subsalicylate 262 mg four times daily, metronidazole 500 mg three to four times daily, and tetracycline 500 mg four times daily. This achieves 80–90% eradication even in areas with high clarithromycin resistance. 1

• If bismuth is unavailable, use 14-day concomitant quadruple therapy (esomeprazole or rabeprazole 40 mg twice daily, amoxicillin 1000 mg twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily) only when local clarithromycin resistance is <15%. 1

• A 14-day course is mandatory; extending therapy from 7 to 14 days improves eradication rates by approximately 5%. 1

• Start eradication treatment as soon as oral feeding is reintroduced after stabilization, rather than waiting for discharge; delaying treatment leads to reduced compliance and loss to follow-up. 3

PPI Therapy Duration

• Continue high-dose PPI (esomeprazole or rabeprazole 40 mg twice daily) for a total of 4–6 weeks for ulcers 1.0–1.5 cm to ensure complete healing. 1

• Maintain full-dose PPI until repeat endoscopy demonstrates complete ulcer healing after confirmed H. pylori eradication. 1

Confirmation of Eradication

• Perform urea breath test or monoclonal stool antigen test at least 4 weeks after completing eradication therapy; discontinue PPI at least 2 weeks before testing to avoid false-negative results. 1, 3

• If eradication fails, initiate second-line 14-day levofloxacin-based triple therapy: levofloxacin 500 mg daily, amoxicillin 1000 mg twice daily, and PPI 40 mg twice daily, avoiding antibiotics used previously. 1

• Successful eradication reduces rebleeding rates from 26% to near-zero in H. pylori-associated bleeding ulcers. 2, 3

Follow-Up Endoscopy

• Schedule repeat endoscopy at 6 weeks after diagnosis for all gastric ulcers to confirm complete healing and exclude malignancy; obtain multiple biopsies from the ulcer site even if it appears healed. 1

• Repeat endoscopy is obligatory for gastric ulcers but generally not necessary for duodenal ulcers after successful H. pylori eradication, unless the patient needs to continue NSAIDs. 1, 3

Management of NSAID-Induced Ulcers

• Discontinue NSAIDs immediately if medically feasible; if NSAIDs must be continued, test for H. pylori and eradicate if positive, as this reduces ulcer risk by 50%. 4, 5

• For H. pylori-negative NSAID ulcers, treat with high-dose PPI for 4–6 weeks; ulcers heal quickly even if NSAIDs are continued. 6

• After healing, provide continuous PPI prophylaxis (full or half healing dose) to prevent recurrence if NSAIDs must be continued long-term, reducing ulcer recurrence risk by 60–80%. 6

• Consider switching to a COX-2 selective inhibitor (e.g., celecoxib) with PPI co-therapy, which reduces complicated ulcer risk by 50–60%. 3, 4

Management of Bleeding Peptic Ulcers

• Initiate high-dose intravenous PPI immediately (80 mg bolus followed by continuous infusion) without delaying urgent endoscopy; pre-endoscopic PPI does not reduce mortality or rebleeding but should be given while arranging endoscopy. 1, 3

• Begin eradication therapy after 72–96 hours of intravenous PPI administration as soon as oral intake resumes; postponing until discharge markedly lowers compliance. 3, 7

• Test all patients with bleeding peptic ulcers for H. pylori; empirical antimicrobial therapy without confirmed infection is not recommended. 2

• Eradication is markedly more effective than PPI alone in preventing rebleeding; failure to eradicate results in 26% rebleeding rate versus near-zero with successful eradication. 2, 3

Management of H. pylori-Negative, Non-NSAID Ulcers (Idiopathic)

• Treat with high-dose PPI or H2-receptor antagonist for 4–6 weeks, followed by long-term maintenance therapy (often half the healing dose) to prevent recurrence. 6

• Some idiopathic ulcers may be sequelae of previous NSAID use even after cessation; maintain long-term acid suppression. 6

Critical Pitfalls to Avoid

• Do not skip repeat endoscopy for gastric ulcers; some malignancies become detectable only after the ulcer has healed. 1

• Never use a 7-day eradication regimen; a full 14-day course is required for optimal success. 1

• Do not postpone eradication therapy; start it promptly when the patient can tolerate oral medication. 1

• Do not test for eradication while the patient is on a PPI; stop the PPI at least 2 weeks before testing. 1, 3

• Do not rely solely on symptom resolution; endoscopic and histologic confirmation of healing is mandatory for gastric ulcers. 1

• Do not use serology to confirm eradication; antibody levels remain elevated long after cure. 1

• Do not use PPI therapy as a substitute for urgent endoscopy in patients with active bleeding; definitive endoscopic evaluation and hemostasis remain essential. 3