What is the first-line treatment for gastritis or peptic ulcer disease?

First-Line Treatment for Gastritis and Peptic Ulcer Disease

Immediate Pharmacological Management

Start standard-dose proton pump inhibitor (PPI) therapy immediately as first-line treatment, with omeprazole 20mg once daily or equivalent, administered 30-60 minutes before breakfast, for 6-8 weeks. 1, 2, 3

• PPIs remain the cornerstone of initial therapy for both gastritis and peptic ulcer disease, providing potent acid suppression that allows mucosal healing 1, 4
• The 6-8 week duration is critical for gastric ulcers specifically, as they require longer healing time than duodenal ulcers (which typically need only 4 weeks) 2, 3
• Do NOT use potassium-competitive acid blockers (P-CABs) like vonoprazan as first-line therapy - despite their theoretical advantages, they should be reserved for PPI failures due to higher costs, limited availability, and less robust long-term safety data 5, 1

Essential H. pylori Testing at Initial Visit

Test ALL patients with gastritis or peptic ulcer disease for H. pylori infection immediately using urea breath test or stool antigen testing. 5, 1, 2

• This is non-negotiable because failure to eradicate H. pylori leads to recurrence rates of 40-50% over 10 years 1, 2
• Urea breath test has 88-95% sensitivity and 95-100% specificity 5
• Stool antigen testing has 94% sensitivity and 92% specificity 5
• If endoscopy is performed, obtain tissue biopsy for H. pylori testing 5

H. pylori Eradication Regimen (If Positive)

First-Line: Bismuth Quadruple Therapy (Preferred)

Bismuth quadruple therapy is now the recommended first-line treatment, replacing the older clarithromycin-based triple therapy due to rising antibiotic resistance. 5

• This regimen is favored because it maintains acceptable success even with metronidazole-resistant strains 5
• Duration: 14 days for optimal eradication rates 5

Alternative First-Line: Standard Triple Therapy (Only in Low Resistance Areas)

Use standard triple therapy ONLY if local clarithromycin resistance is <15%: 5, 4

• PPI standard dose twice daily
• Clarithromycin 500mg twice daily
• Amoxicillin 1000mg twice daily (or metronidazole 500mg twice daily if penicillin allergic)
• Duration: 14 days 5

The critical caveat here is that clarithromycin resistance has been rising globally, making triple therapy success rates decline from 90% in the 1990s to much lower rates today 5. This is why bismuth quadruple therapy has become preferred.

Alternative: Concomitant Non-Bismuth Quadruple Therapy

If bismuth is unavailable and clarithromycin resistance is high, use concomitant 4-drug therapy: 5

• PPI twice daily + amoxicillin 1000mg twice daily + metronidazole 500mg twice daily + clarithromycin 500mg twice daily
• Duration: 10-14 days 5

Second-Line Therapy (If First-Line Fails)

Use levofloxacin-based triple therapy if initial eradication fails: 5, 1, 4

• PPI standard dose twice daily
• Levofloxacin 500mg once daily (or 250mg twice daily)
• Amoxicillin 1000mg twice daily
• Duration: 10 days 5, 1

Critical pitfall: Avoid using clarithromycin, levofloxacin, or metronidazole in subsequent attempts if they were used previously, as resistance is likely the cause of failure 5

NSAID-Associated Ulcers: Special Considerations

Discontinue NSAID therapy immediately whenever possible. 1, 2

• If NSAIDs cannot be stopped, continue PPI therapy long-term 1, 2
• For patients requiring ongoing NSAIDs with moderate bleeding risk: use either NSAID + PPI OR selective COX-2 inhibitor alone 6
• For high-risk patients: use selective COX-2 inhibitor + PPI combination 6
• H. pylori infection increases bleeding risk in NSAID users, making eradication even more critical 6

Bleeding Peptic Ulcers: Escalated Management

For bleeding ulcers with high-risk stigmata after endoscopic hemostasis, use high-dose PPI therapy: 1, 2

• 80mg IV bolus followed by 8mg/hour continuous infusion for 72 hours 5, 1, 2
• Then transition to standard oral PPI for 6-8 weeks 1
• Important: PPI therapy should NOT replace urgent endoscopy in actively bleeding patients 1, 2

Follow-Up Strategy

Reassess symptoms at 4 weeks and complete the full 6-8 week PPI course regardless of symptom resolution. 2

• Consider endoscopy if no improvement at 4 weeks 2
• Confirm H. pylori eradication after treatment completion using urea breath test or stool antigen test (performed at least 4 weeks after completing antibiotics and 2 weeks after stopping PPI) 1
• If symptoms recur after initial improvement, consider on-demand PPI therapy 4

Common Pitfalls to Avoid

• Never assume symptom improvement with PPI means acid-peptic disease - PPIs have anti-inflammatory effects independent of acid suppression 7
• Never skip H. pylori testing - this is the single most important factor in preventing recurrence 1, 2
• Never use shorter than 14-day antibiotic courses - this compromises eradication rates 5
• Be aware that PPIs may reduce absorption of medications requiring acidic environment (e.g., certain antiretrovirals, antifungals) 1