What is the first-line treatment for a patient with a confirmed diagnosis of H pylori (Helicobacter pylori) infection?

H. pylori Treatment

First-Line Treatment Recommendation

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline, achieving 80-90% eradication rates even in areas with high antibiotic resistance. 1

Specific First-Line Regimen Components

The optimal bismuth quadruple therapy regimen includes:

• Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs as they increase cure rates by 8-12%) 1
• Bismuth subsalicylate 262 mg (2 tablets) four times daily 1
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline 500 mg four times daily 1
• Duration: 14 days mandatory (improves eradication by ~5% compared to shorter regimens) 1

Critical Administration Details

• Take PPI 30 minutes before meals on an empty stomach 1
• Do not use concomitant antacids with the PPI 1
• Bismuth has no described bacterial resistance, making this regimen highly effective 1
• Bismuth's synergistic effect overcomes metronidazole resistance even when present in vitro 1

Why Bismuth Quadruple Therapy is Preferred

Clarithromycin resistance now exceeds 15-20% in most of North America and Central, Western, and Southern Europe, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target. 1 When H. pylori strains are clarithromycin-resistant, eradication rates with triple therapy drop to approximately 20% compared to 90% with susceptible strains. 1

Bismuth quadruple therapy uses antibiotics from the WHO "Access group" (tetracycline and metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective. 1

Alternative First-Line Option (Only in Low Resistance Areas)

In areas with documented clarithromycin resistance below 15%, triple therapy may be considered: 1

• Esomeprazole or rabeprazole 40 mg twice daily 1
• Clarithromycin 500 mg twice daily 1
• Amoxicillin 1000 mg twice daily 2, 3
• Duration: 14 days 1

Critical caveat: Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1 If local data is unavailable, assume high resistance and use bismuth quadruple therapy. 1

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Fails

Levofloxacin triple therapy for 14 days (if no prior fluoroquinolone exposure): 1

• Esomeprazole or rabeprazole 40 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Levofloxacin 500 mg once daily (or 250 mg twice daily) 1

Critical warning: Do not use levofloxacin in patients with chronic bronchopneumopathy or other conditions where they may have received prior fluoroquinolone exposure for any indication, as cross-resistance exists within the fluoroquinolone family. 1

If Triple Therapy Fails

Bismuth quadruple therapy for 14 days (if not previously used) 1

Never repeat clarithromycin if it was in the failed regimen, as resistance develops rapidly after exposure and eradication rates drop from 90% to 20% with resistant strains. 1

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1

Rifabutin Triple Therapy (Third-Line)

• Rifabutin 150 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• High-dose PPI twice daily 1
• Duration: 14 days 1

Rifabutin resistance is extremely rare, making this an effective rescue option. 1 However, reserve this for patients who have failed previous eradication attempts with other antibiotics due to potential myelotoxicity. 1

High-Dose Dual Therapy (Alternative Rescue)

• Amoxicillin 2-3 grams daily in 3-4 split doses 1
• High-dose PPI (double standard dose) twice daily 1
• Duration: 14 days 1

Special Populations

Penicillin Allergy

Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 1 Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as most patients who think they are allergic are found not to have a true allergy. 1

If bismuth is unavailable and clarithromycin resistance is <15%:

• High-dose PPI twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days 1

Pediatric Patients

Treatment should only be conducted by pediatricians in specialist centers. 1 First-line options include PPI + amoxicillin + clarithromycin, PPI + amoxicillin + metronidazole, or bismuth + amoxicillin + metronidazole. 1

Verification of Eradication

Test for eradication success at least 4 weeks after completion of therapy using urea breath test or validated monoclonal stool antigen test. 1, 4

• Discontinue PPI at least 2 weeks before testing to avoid false-negative results 1, 4
• Never use serology to confirm eradication—antibodies may persist long after successful treatment 1

Testing is mandatory in patients with complicated peptic ulcer disease, gastric ulcer, low-grade gastric MALT lymphoma, and after treatment failure. 1

Critical Pitfalls to Avoid

• Never use standard-dose PPI once daily—always use high-dose (twice daily) PPI, as inadequate dosing significantly reduces treatment efficacy 1, 5
• Never use 7-day regimens—14 days is mandatory for optimal eradication rates 1
• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1
• Do not use levofloxacin empirically as first-line therapy, as this accelerates resistance development and eliminates a valuable rescue option 1
• Avoid concomitant, sequential, or hybrid therapies, as they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1

Patient Factors Affecting Success

• Smoking increases risk of eradication failure (odds ratio 1.95) 1, 4
• High BMI reduces drug concentrations at the gastric mucosal level, increasing failure risk 1, 4
• Poor compliance accounts for >10% of treatment failures—address adherence proactively 1, 4
• Diarrhea occurs in 21-41% of patients during the first week due to disruption of gut microbiota; consider adjunctive probiotics to reduce this risk and improve compliance 1

Special Clinical Indications for H. pylori Eradication

• Active or past history of peptic ulcer disease 1
• Before starting NSAID treatment (mandatory in patients with peptic ulcer history) 1
• Bleeding peptic ulcer—start eradication immediately when oral feeding is reintroduced, as eradication reduces rebleeding rate from 26% to near zero 1
• Low-grade gastric MALT lymphoma—eradication is first-line treatment with 60-80% cure rates in early-stage cases 1
• Unexplained iron-deficiency anemia, idiopathic thrombocytopenic purpura, or vitamin B12 deficiency 1
• Family history of gastric cancer—eradication is effective in preventing gastric cancer if given before preneoplastic conditions develop 1