What is the recommended medication regimen for an adult with gastritis, including first‑line acid suppression, Helicobacter pylori eradication if present, and management of NSAID‑induced gastritis?

Gastritis Medication Regimen

First-Line Acid Suppression

For adults with gastritis, high-dose proton pump inhibitors (PPIs) twice daily are the cornerstone of initial therapy, with esomeprazole or rabeprazole 40 mg twice daily preferred over other PPIs because they increase symptom relief and mucosal healing by 8–12% compared to standard-dose options. 1

• Take PPIs 30 minutes before meals on an empty stomach, without concomitant antacids, to maximize acid suppression 2
• Pantoprazole should be avoided when possible because 40 mg pantoprazole provides acid-suppression equivalent to only 9 mg omeprazole 1, 2
• Alternative acceptable twice-daily doses include lansoprazole 30 mg, omeprazole 20 mg, or standard esomeprazole/rabeprazole 20 mg 1
• H2-receptor antagonists (e.g., ranitidine, famotidine) provide faster symptom relief than PPIs but are significantly less effective for healing gastric lesions and should be reserved for breakthrough symptoms only 1

Helicobacter pylori Testing and Eradication

Every adult with gastritis must be tested for H. pylori using urea breath test (sensitivity 88–95%, specificity 95–100%) or monoclonal stool antigen test (sensitivity 94%, specificity 92%), and if positive, receive eradication therapy immediately because H. pylori gastritis invariably progresses to atrophic gastritis, intestinal metaplasia, and carries increased gastric cancer risk. 1, 3, 4

First-Line H. pylori Eradication: Bismuth Quadruple Therapy (14 Days)

Bismuth quadruple therapy for 14 days is the definitive first-line regimen, achieving 80–90% eradication rates even in regions with high clarithromycin and metronidazole resistance (>15–20%). 2, 3

The regimen consists of:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 2, 3
• Bismuth subsalicylate 262 mg (two tablets) four times daily 2
• Metronidazole 500 mg three to four times daily 2, 3
• Tetracycline 500 mg four times daily 2, 3, 5
• Duration: 14 days is mandatory—extending from 7 to 14 days improves eradication by approximately 5% 2, 4

Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy

Use only when bismuth is unavailable AND regional clarithromycin resistance is documented <15%. 2

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg) 2
• Amoxicillin 1000 mg twice daily 2, 5
• Clarithromycin 500 mg twice daily 2
• Metronidazole 500 mg twice daily 2
• Duration: 14 days 2

Second-Line After First-Line Failure

After clarithromycin-based or bismuth quadruple therapy failure, use levofloxacin triple therapy for 14 days—but ONLY if the patient has never received fluoroquinolones for any indication. 2

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg) 2
• Amoxicillin 1000 mg twice daily 2, 5
• Levofloxacin 500 mg once daily 2
• Duration: 14 days 2

Third-Line and Rescue Options

• After two failed eradication attempts with confirmed adherence, obtain antibiotic susceptibility testing to guide further therapy 2, 4
• Rifabutin triple therapy: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + high-dose PPI twice daily for 14 days 2
• High-dose dual therapy: amoxicillin 2–3 g daily divided into 3–4 doses + high-dose PPI twice daily for 14 days 2

Confirmation of H. pylori Eradication (Mandatory)

Test-of-cure is required for all patients using urea breath test or monoclonal stool antigen test performed ≥4 weeks after completing antibiotics and ≥2 weeks after stopping PPIs. 2, 3

• Never use serology for test-of-cure because antibodies persist long after successful eradication 2
• Failure to confirm eradication allows ongoing progression to atrophic gastritis and gastric cancer 1, 3

NSAID-Induced Gastritis Management

For adults with NSAID-induced gastritis, immediately discontinue all NSAIDs if clinically feasible; if NSAIDs cannot be stopped, continue high-dose PPI therapy indefinitely for gastroprotection and use the lowest effective NSAID dose for the shortest duration. 1

Risk Stratification and Gastroprotection Strategy

High-risk patients (previous peptic ulcer or ulcer complication, age >65 years, concurrent corticosteroid use, concurrent anticoagulation/antiplatelet therapy, high-dose or multiple NSAID use) require intensive gastroprotection: 1

• Combine a selective COX-2 inhibitor with a PPI for maximum protection 1
• H. pylori eradication should be performed before starting long-term NSAID therapy, especially in patients with previous ulcer history 1, 4
• In patients already on NSAIDs with H. pylori infection, both PPI therapy AND H. pylori eradication are necessary—eradication alone is insufficient 1

Moderate-risk patients can receive either:

• NSAID + PPI combination, OR
• Selective COX-2 inhibitor monotherapy 6

Adjunctive Gastroprotection (When PPIs Insufficient)

• Misoprostol 200 mcg four times daily with food reduces NSAID-associated gastric ulcers by 74% but causes diarrhea and abdominal pain in ~20% of patients, limiting tolerability 1, 7
• If 200 mcg four times daily cannot be tolerated, reduce to 100 mcg four times daily 7
• H2-receptor antagonists are NOT recommended for gastroprotection because they only reduce duodenal (not gastric) ulcer risk 1

Special Populations and Scenarios

Penicillin Allergy

• Bismuth quadruple therapy is the first-choice regimen because it contains tetracycline, not amoxicillin 2
• After first-line failure, consider formal penicillin allergy testing because many reported allergies are not true 2

Renal Impairment (Amoxicillin Dosing)

• GFR 10–30 mL/min: amoxicillin 500 mg every 12 hours 5
• GFR <10 mL/min: amoxicillin 500 mg every 24 hours 5
• Hemodialysis: amoxicillin 500 mg every 24 hours, with additional dose during and at end of dialysis 5

Erosive Gastritis with H. pylori

• Patients with erosive gastritis and H. pylori require assessment for atrophic changes because the combination significantly increases gastric cancer risk 3
• Those with severe atrophy, corpus-predominant gastritis, or intestinal metaplasia need endoscopic surveillance every 3 years after eradication 3

Autoimmune Gastritis

• Check antiparietal cell antibodies and anti-intrinsic factor antibodies 1
• Evaluate for anemia due to vitamin B-12 and iron deficiencies 1
• Screen for concomitant autoimmune thyroid disease 1
• Consider surveillance endoscopy every 3 years in individuals with advanced atrophic gastritis 1

Critical Pitfalls to Avoid

• Never use clarithromycin-based triple therapy empirically in North America or most of Europe where clarithromycin resistance exceeds 15–20% and eradication rates fall to ~70% 2
• Never shorten H. pylori therapy below 14 days—this reduces eradication success by approximately 5% 2, 4
• Never use once-daily PPI dosing for H. pylori eradication; twice-daily high-dose PPI is mandatory 2
• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 2
• Never combine multiple NSAIDs because this dramatically increases gastrointestinal bleeding risk 1
• Never assume buffered or coated aspirin decreases GI risk—it does not 1
• Never omit test-of-cure after H. pylori treatment—persistent infection permits ongoing progression toward gastric cancer 2, 3
• Inadequate PPI dosing (wrong timing relative to meals) reduces effectiveness—PPIs must be taken 30 minutes before eating 2, 1
• Long-term PPI use in H. pylori-positive patients accelerates progression to corpus-predominant and atrophic gastritis, making eradication particularly important 1, 4