Management of Peptic Ulcer Disease
Initial Diagnostic Approach
All patients with suspected peptic ulcer disease should undergo Helicobacter pylori testing as the cornerstone of management, since H. pylori infection accounts for approximately 42% of cases and NSAID use for 36%, with eradication dramatically reducing recurrence from 50-60% to 0-2%. 1
Who Needs Endoscopy vs. Test-and-Treat
- Patients under 60 years without alarm features should receive noninvasive H. pylori testing (urea breath test or stool antigen test) followed by treatment if positive—this test-and-treat strategy is appropriate when gastric cancer risk is low 2, 3
- Patients 60 years or older with new dyspepsia require esophagogastroduodenoscopy (EGD) to exclude malignancy 2
- Any patient with alarm features (bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia, odynophagia, recurrent vomiting, family history of gastric cancer, previous gastric surgery) requires immediate EGD regardless of age 3, 2
Optimal H. pylori Testing Methods
- Urea breath test (sensitivity 88-95%, specificity 95-100%) and stool antigen test (sensitivity 94%, specificity 92%) are the preferred noninvasive methods 4, 3
- Serologic tests are less accurate and cannot confirm eradication—never use serology to document cure 3
- Endoscopic biopsy provides tissue diagnosis when EGD is performed 4
- Discontinue PPIs at least 2 weeks before testing to avoid false-negative results 5, 6
First-Line H. pylori Eradication Therapy
Bismuth quadruple therapy for 14 days is the definitive first-line treatment, achieving 80-90% eradication rates even in regions with high clarithromycin resistance (>15%), which now includes most of North America and Europe. 5, 6
Bismuth Quadruple Therapy Regimen (14 days)
- Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs; increases cure rates by 8-12%) 5, 6
- Bismuth subsalicylate 262 mg (two tablets) four times daily 5, 6
- Metronidazole 500 mg three to four times daily 5, 6
- Tetracycline 500 mg four times daily 5, 6
Key optimization factors:
- Take PPI 30 minutes before meals on an empty stomach 5
- The 14-day duration is mandatory—extending from 7 to 14 days improves eradication by approximately 5% 5, 6
- Bismuth has no documented bacterial resistance and synergizes with metronidazole to overcome resistance 5
Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy (14 days)
Use only when bismuth is unavailable AND local clarithromycin resistance is documented <15%: 5, 6
- Esomeprazole or rabeprazole 40 mg twice daily 5
- Amoxicillin 1000 mg twice daily 5
- Clarithromycin 500 mg twice daily 5
- Metronidazole 500 mg twice daily 5
Critical pitfall: Standard triple therapy (PPI + clarithromycin + amoxicillin) should be abandoned when regional clarithromycin resistance exceeds 15-20%, as eradication rates drop from 90% to approximately 20% with resistant strains 5
Second-Line Therapy After First-Line Failure
If bismuth quadruple therapy fails and the patient has no prior fluoroquinolone exposure, prescribe levofloxacin triple therapy for 14 days. 5, 6
Levofloxacin Triple Therapy (14 days)
- Esomeprazole or rabeprazole 40 mg twice daily 5
- Amoxicillin 1000 mg twice daily 5
- Levofloxacin 500 mg once daily 5
Critical considerations:
- Never reuse clarithromycin or levofloxacin if they were in a failed regimen—resistance develops rapidly after exposure 5, 6
- Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary resistance) 5
- Avoid levofloxacin in patients with prior fluoroquinolone exposure for any indication (e.g., respiratory infections) 5
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, obtain antibiotic susceptibility testing to guide further treatment. 5, 6
Rifabutin Triple Therapy (14 days)
- Esomeprazole or rabeprazole 40 mg twice daily 5
- Rifabutin 150 mg twice daily 5
- Amoxicillin 1000 mg twice daily 5
Note: Rifabutin resistance is rare, making this an effective rescue option 5
High-Dose Dual Therapy (14 days)
Confirmation of Eradication
Test for eradication success at least 4 weeks after completing therapy using urea breath test or monoclonal stool antigen test. 5, 6
- Discontinue PPI at least 2 weeks before testing to avoid false-negative results 5, 6
- Never use serology to confirm eradication—antibodies persist long after successful treatment 5
- Confirmation is mandatory for gastric ulcers, complicated ulcers, bleeding ulcers, and gastric MALT lymphoma 4, 7
Management of NSAID-Induced Ulcers
Prevention Strategies
H. pylori eradication is mandatory before starting NSAID treatment in patients with a history of peptic ulcer—this reduces ulcer risk by approximately 50%. 4, 6
- Test for H. pylori in all aspirin users with a history of gastroduodenal ulcer—the long-term incidence of peptic ulcer bleeding is low after successful eradication even without gastroprotective treatment 4, 6
- Coadminister a PPI (e.g., omeprazole, lansoprazole) with chronic NSAID use to reduce ulcer risk 2, 1
- Consider switching to celecoxib (selective COX-2 inhibitor) which has less effect on gastric mucosa 2
- Misoprostol is an alternative gastroprotective agent but less well-tolerated than PPIs 3
Treatment of Active NSAID-Induced Ulcers
- Discontinue the NSAID if possible—this heals 95% of ulcers and reduces recurrence from 40% to 9% 1
- If NSAID cannot be discontinued: switch to a less ulcerogenic agent (e.g., from ketorolac to ibuprofen), add a PPI, and eradicate H. pylori if present 1
- Continue PPI therapy until ulcer healing is confirmed endoscopically 1
Critical synergy: The combination of H. pylori infection and NSAID use increases bleeding ulcer risk more than sixfold 2
Special Clinical Scenarios
Bleeding Peptic Ulcer
Initiate H. pylori eradication therapy immediately when oral feeding is resumed after endoscopic hemostasis—delaying treatment reduces compliance and increases loss to follow-up. 4, 7
- All patients with bleeding peptic ulcer should undergo H. pylori testing 4
- Eradication reduces rebleeding rate from 26% to near-zero 4, 7
- Continue high-dose PPI until eradication is confirmed in complicated duodenal ulcer; for gastric ulcer, maintain PPI until endoscopic healing is documented 7
- High-dose IV esomeprazole (80 mg bolus followed by 8 mg/h infusion) provides acute acid suppression but does not eradicate H. pylori 5
Perforated Peptic Ulcer
- Start eradication therapy when oral feeding resumes after Graham patch repair or simple closure 7
- Eradication after perforation reduces ulcer recurrence from ~26% to near-zero 7
Gastric MALT Lymphoma
H. pylori eradication is the first-line treatment for low-grade gastric marginal zone (MALT) lymphoma, achieving cure rates of 60-80% in early-stage cases. 4, 6
- When t(11,18) translocation is present, eradication is usually ineffective and adjunctive treatments are needed 5
Gastric Ulcer vs. Duodenal Ulcer
- Gastric ulcers require endoscopic follow-up to ensure complete healing and exclude malignancy 4
- Continue PPI after eradication until gastric ulcer healing is confirmed endoscopically 4
- Duodenal ulcers do not require prolonged PPI after successful eradication in uncomplicated cases 4
Patients with Penicillin Allergy
Bismuth quadruple therapy is the first-choice regimen because it contains tetracycline instead of amoxicillin. 5, 6
- Consider penicillin allergy testing after first-line failure, as most reported allergies are not true allergies 5
Critical Pitfalls to Avoid
- Never use once-daily PPI dosing for eradication—twice-daily high-dose PPI is mandatory 5, 6
- Never shorten treatment below 14 days—this reduces eradication success by ~5% 5, 6
- Never repeat clarithromycin or levofloxacin if they were in a failed regimen 5, 6
- Never use pantoprazole for eradication—its acid-suppression potency is markedly lower (40 mg pantoprazole ≈ 9 mg omeprazole equivalent) 5
- Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance 5
- Never use empiric triple therapy when clarithromycin resistance exceeds 15% 5, 6
- Never delay eradication therapy in bleeding or perforated ulcers beyond reintroduction of oral feeding 4, 7
Patient Factors Affecting Treatment Success
- Smoking increases eradication failure risk (odds ratio 1.95) 5, 6
- High BMI increases failure risk due to lower drug concentrations at the gastric mucosal level 5, 6
- Poor compliance accounts for >10% of treatment failures—provide clear education on dosing, expected side effects, and importance of completing the full course 5
- Diarrhea occurs in 21-41% of patients during the first week—consider adjunctive probiotics to reduce this risk and improve compliance 5, 6