What is the recommended treatment for Helicobacter pylori (H. pylori) positive patients?

Treatment of Helicobacter pylori Infection

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth subsalicylate (262 mg four times daily) or bismuth subcitrate (120 mg four times daily), metronidazole 500 mg three to four times daily, and tetracycline 500 mg four times daily. 1, 2

First-Line Treatment Selection

The shift away from traditional triple therapy is driven by rising clarithromycin resistance, which now exceeds 15% in most regions of North America and Europe. 1, 2 When H. pylori strains are clarithromycin-resistant, eradication rates with triple therapy plummet from 90% to approximately 20%. 1

Bismuth quadruple therapy achieves 80-90% eradication rates even against strains with dual resistance to clarithromycin and metronidazole because bismuth has synergistic effects that overcome in vitro metronidazole resistance, and no bacterial resistance to bismuth has been described. 1, 2, 3

Alternative First-Line Option When Bismuth is Unavailable

If bismuth is not available, concomitant non-bismuth quadruple therapy is the preferred alternative: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days. 1, 2 This regimen administers all antibiotics simultaneously, preventing resistance development during treatment. 1

Limited Role for Triple Therapy

Triple therapy (PPI + clarithromycin + amoxicillin) should only be considered in areas with documented clarithromycin resistance <15%, which is now rare in most developed countries. 1, 2 Standard triple therapy should be abandoned when regional clarithromycin resistance exceeds 15-20%. 1

Critical Treatment Optimization Factors

PPI Dosing and Timing

High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate and significantly reduces treatment efficacy. 1, 2 PPIs should be taken 30 minutes before meals on an empty stomach, without concomitant use of other antacids. 1 Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% compared to other PPIs. 1, 3

Treatment Duration

All H. pylori eradication regimens should be given for 14 days, not 7-10 days. 1, 2, 4 Extending treatment duration from 7 to 14 days improves eradication success by approximately 5%. 1, 2

Specific Antibiotic Considerations

• Tetracycline 500 mg four times daily is essential—doxycycline should never be substituted as it produces significantly inferior results. 3
• Metronidazole at higher doses (1.5-2 g daily in divided doses) improves eradication rates even with resistant strains when combined with bismuth. 1
• Amoxicillin and tetracycline can be re-used in subsequent regimens because resistance to these agents remains rare (1-5%). 1

Second-Line Treatment After First-Line Failure

After failure of first-line therapy, select an alternative regimen based on prior antibiotic exposure—never repeat clarithromycin or levofloxacin if previously used. 1, 2

Recommended Second-Line Options

1. Bismuth quadruple therapy for 14 days (if not used first-line) 1, 2

2. Levofloxacin-based triple therapy: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) for 14 days 1, 2

   • Caution: Rising levofloxacin resistance rates (11-30% primary, 19-30% secondary) limit this option. 1 Do not use levofloxacin empirically as first-line therapy. 1

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible. 1, 2, 3 This is the current standard recommendation. 1

Rescue Options

1. Rifabutin-based triple therapy: Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily for 14 days 1, 2

   • Rifabutin should be reserved for patients who have failed multiple previous attempts, as resistance to rifabutin and amoxicillin remains extremely rare. 1

2. High-dose dual amoxicillin-PPI therapy: Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily for 14 days 1

Special Populations

Penicillin Allergy

Bismuth quadruple therapy is the first choice in patients with penicillin allergy because it contains tetracycline, not amoxicillin. 1, 3 However, verify penicillin allergy history—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare. 1

Pediatric Patients

Treatment of H. pylori in children should only be conducted by pediatricians in specialist centers. 1 Fluoroquinolones and tetracyclines cannot be used in children, considerably limiting treatment options. 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 Never use serology to confirm eradication—antibodies may persist long after successful treatment. 1

Managing Treatment Side Effects

Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota. 1 Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance. 1, 2

Common Pitfalls to Avoid

• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1
• Avoid repeating clarithromycin if the patient has prior macrolide exposure for any indication, as cross-resistance is universal within the macrolide family. 1
• Patient factors affecting success: Smoking increases eradication failure risk (OR 1.95), and high BMI leads to lower drug concentrations at the gastric mucosal level. 1 Address compliance issues, as more than 10% of patients are poor compliers. 1
• Take amoxicillin at the start of a meal to minimize gastrointestinal intolerance. 5