Treatment of H. pylori Gastritis
Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori gastritis, consisting of a high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2
First-Line Treatment Regimen
The preferred regimen achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance 1, 2:
- PPI component: Esomeprazole or rabeprazole 40 mg twice daily (taken 30 minutes before meals on an empty stomach) 1, 2
- Bismuth: Bismuth subsalicylate 262 mg (2 tablets) four times daily 2
- Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1, 2
- Tetracycline: 500 mg four times daily 1, 2
- Duration: 14 days mandatory 1, 2
This regimen is superior because bacterial resistance to bismuth is extremely rare, and the synergistic effect of bismuth overcomes metronidazole resistance even when present in vitro 1, 2, 3.
Alternative First-Line Option When Bismuth is Unavailable
Concomitant non-bismuth quadruple therapy is the recommended alternative 1, 2, 3:
- PPI: Esomeprazole or rabeprazole 40 mg twice daily 2
- Amoxicillin: 1000 mg twice daily 1, 2, 4
- Clarithromycin: 500 mg twice daily 1, 2
- Metronidazole: 500 mg twice daily 1, 2
- Duration: 14 days 1, 2
This regimen should only be used when bismuth is truly unavailable, as it contributes more to global antibiotic resistance 1, 2.
Critical Optimization Factors
PPI Selection and Dosing
High-dose PPI twice daily is mandatory and increases cure rates by 8-12% compared to standard dosing 1, 2, 3. Esomeprazole 40 mg twice daily equals 32 mg omeprazole equivalent, while rabeprazole 40 mg twice daily equals 36 mg omeprazole equivalent 1. Avoid pantoprazole, as 40 mg pantoprazole equals only 9 mg omeprazole 1.
Treatment Duration
Extending treatment from 7 to 14 days improves eradication success by approximately 5% 1, 2, 3. The 14-day duration is non-negotiable for optimal outcomes 2, 3.
Timing of Administration
PPIs must be taken 30 minutes before meals on an empty stomach, without concomitant antacids, to maximize efficacy 2, 4.
Second-Line Treatment After First-Line Failure
After bismuth quadruple therapy failure, levofloxacin-based triple therapy is recommended (if no prior fluoroquinolone exposure) 1, 2, 3:
- PPI: Esomeprazole or rabeprazole 40 mg twice daily 2
- Amoxicillin: 1000 mg twice daily 1, 2, 4
- Levofloxacin: 500 mg once daily (or 250 mg twice daily) 1, 2
- Duration: 14 days 1, 2
Critical caveat: Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary resistance), and the FDA recommends fluoroquinolones as a last choice due to serious side effects 1, 2. Never use levofloxacin if the patient has had prior fluoroquinolone exposure for any indication 1, 2, 3.
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient compliance, antibiotic susceptibility testing should guide further treatment 1, 2, 3.
Rifabutin-based triple therapy is a reasonable rescue option 1, 2:
- Rifabutin: 150 mg twice daily 2
- Amoxicillin: 1000 mg twice daily 2, 4
- PPI: Esomeprazole or rabeprazole 40 mg twice daily 2
- Duration: 14 days 2
Rifabutin resistance remains rare, making this an effective salvage regimen 2.
High-dose dual amoxicillin-PPI therapy is an alternative rescue option 1, 2:
- Amoxicillin: 2-3 grams daily in 3-4 divided doses 2
- PPI: Double standard dose twice daily 2
- Duration: 14 days 2
Special Populations
Penicillin Allergy
Bismuth quadruple therapy is the first choice, as it contains tetracycline rather than amoxicillin 2. However, consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains extremely rare (<5%) 2.
Pediatric Patients
Treatment should only be conducted by pediatric gastroenterologists in specialist centers 2. Avoid fluoroquinolones and tetracyclines in children 3.
Verification of Eradication
Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation 1, 2, 3. Never use serology to confirm eradication, as antibodies persist long after successful treatment 2, 3.
Common Pitfalls to Avoid
- Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 2, 3
- Never use standard triple therapy (PPI + clarithromycin + amoxicillin) empirically in areas where clarithromycin resistance exceeds 15-20%, which now includes most of North America and Europe 1, 2, 3
- Never use standard-dose PPI once daily—this is inadequate and significantly reduces efficacy 2, 3
- Never use treatment durations shorter than 14 days when aiming for optimal eradication rates 1, 2, 3
- Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 2
- Never use sequential or hybrid therapies—these include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1, 2
Patient Factors Affecting Success
Smoking increases the risk of eradication failure (odds ratio 1.95) 2. High BMI, particularly in obese patients, increases failure risk due to lower drug concentrations at the gastric mucosal level 2. Poor compliance accounts for more than 10% of treatment failures 2. Address these factors proactively to maximize treatment success.
Adjunctive Therapies
Probiotics can reduce antibiotic-associated diarrhea (which occurs in 21-41% of patients during the first week) and improve compliance, though evidence for increased eradication rates is limited 2, 3. Consider probiotics primarily for symptom management rather than as a strategy to improve eradication 2, 3.