What is the recommended treatment regimen for Helicobacter pylori infection?

Helicobacter pylori Treatment

For first-line treatment of H. pylori infection, use 14-day bismuth quadruple therapy (bismuth ~300mg four times daily, metronidazole 500mg three times daily, tetracycline 500mg four times daily, and a PPI twice daily) as the preferred regimen due to increasing global clarithromycin resistance. 1

First-Line Treatment Selection

The choice of first-line therapy depends critically on local clarithromycin resistance rates:

In Areas with High Clarithromycin Resistance (≥15%)

• Bismuth quadruple therapy for 14 days is the preferred first-line treatment 1, 2, 3

  • Bismuth ~300mg four times daily
  • Metronidazole 500mg three times daily
  • Tetracycline 500mg four times daily
  • PPI twice daily (high-dose)
  • Duration: 14 days 4

• Alternative: Concomitant (non-bismuth quadruple) therapy for 14 days 1, 3

  • Clarithromycin 500mg twice daily
  • Amoxicillin 1g twice daily
  • Metronidazole 500mg twice daily
  • PPI twice daily
  • Duration: 14 days 4

The rationale for bismuth quadruple therapy as first-line is compelling: bacterial resistance to bismuth is extremely rare, making it effective even against metronidazole-resistant strains 1. Global clarithromycin resistance has increased dramatically from 9% in 1998 to 17.6% in 2008-2009, rendering standard triple therapy unacceptable in most regions 1, 2.

In Areas with Low Clarithromycin Resistance (<15%)

• Clarithromycin-based triple therapy for 14 days may be considered 1, 2, 3

  • Clarithromycin 500mg twice daily
  • Amoxicillin 1g twice daily (or metronidazole 500mg twice daily)
  • PPI twice daily
  • Duration: 14 days 4

• However, bismuth quadruple therapy remains a valid first-line option even in low-resistance areas 1

Critical Treatment Optimization Strategies

High-Dose PPI Administration

• Always use high-dose PPI (twice daily), not standard dosing 1, 2
• High-dose PPI increases eradication efficacy by 6-10% compared to standard doses 1, 2
• Standard doses: pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, rabeprazole 20mg 4
• High-dose means double the standard dose 4
• Administer 30 minutes before eating on an empty stomach 4
• Avoid concomitant use of H2-receptor antagonists 4

Treatment Duration

• Extend treatment to 14 days, not 7-10 days 1, 2, 3
• Extending from 7 to 14 days improves eradication success by approximately 5% 1, 2

Medication Timing

• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 5

Second-Line Treatment After First-Line Failure

After failure of clarithromycin-containing first-line therapy:

Option 1: Bismuth Quadruple Therapy (if not previously used)

• Same regimen as described above for 14 days 1, 2, 3

Option 2: Levofloxacin-Based Triple Therapy

• Levofloxacin 500mg once daily 4, 1, 2
• Amoxicillin 1g twice daily 4, 1
• PPI twice daily (high-dose) 4
• Duration: 14 days 4, 1

Critical caveat: Avoid levofloxacin if the patient has had prior fluoroquinolone exposure for any indication, as this dramatically increases resistance risk 1. In populations with known high levofloxacin resistance, this regimen should be avoided 4.

Third-Line and Rescue Therapy

After two failed eradication attempts with confirmed patient adherence, H. pylori susceptibility testing should be performed to guide subsequent regimens 4, 3.

If Susceptibility Testing is Available:

• Tailor antibiotic selection based on resistance patterns 4, 3
• Options include rifabutin triple therapy, high-dose dual therapy (PPI + amoxicillin), or levofloxacin quadruple therapy depending on susceptibility 4

If Susceptibility Testing is Unavailable:

• Use antibiotics not previously administered or for which resistance is unlikely 3
• Consider: amoxicillin, tetracycline, bismuth, or furazolidone 3

Rifabutin-Based Triple Therapy (Rescue Option)

• Rifabutin 150-300mg daily 4, 1
• Amoxicillin 1g twice daily 4
• PPI twice daily (high-dose) 4
• Duration: 10 days 4
• Rifabutin can be prescribed without prior sensitivity testing since rifabutin and amoxicillin resistance are rare 4

High-Dose Dual Therapy (Alternative Rescue)

• Amoxicillin 2-3g daily in 3-4 split doses 4
• PPI high-dose twice daily 4
• Duration: 14 days 4

Special Populations and Modifications

Penicillin Allergy

• In true penicillin allergy, replace amoxicillin with tetracycline 1
• Verify allergy with testing if appropriate before abandoning amoxicillin-based regimens 4

Renal Impairment

• Patients with GFR <30 mL/min should NOT receive the 875mg amoxicillin dose 5
• GFR 10-30 mL/min: 500mg or 250mg every 12 hours 5
• GFR <10 mL/min: 500mg or 250mg every 24 hours 5
• Hemodialysis: 500mg or 250mg every 24 hours, with additional dose during and at end of dialysis 5

Pediatric Patients

• Fluoroquinolones and tetracyclines should not be used in children 1
• For children ≥3 months and <40kg: dose amoxicillin at 25-45 mg/kg/day divided doses depending on severity 5
• For children <12 weeks: maximum 30mg/kg/day amoxicillin divided every 12 hours due to immature renal function 5

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, as antibodies persist long after successful treatment 1, 2

Adjunctive Therapies

Probiotics

• Probiotics can reduce antibiotic-associated side effects, particularly diarrhea 1, 3
• Evidence for increased eradication rates is limited 1
• For refractory H. pylori infection, probiotics are of unproven benefit and should be considered experimental 4

Common Pitfalls to Avoid

1. Inadequate PPI dosing is a major cause of treatment failure 1, 2

   • Always prescribe high-dose (twice daily) PPI, not standard dosing

2. Never repeat antibiotics to which the patient has been previously exposed 1

   • Especially avoid repeating clarithromycin or levofloxacin after prior exposure

3. Do not use standard triple therapy in areas with clarithromycin resistance >15-20% 1, 2

   • Eradication rates become unacceptably low (<80%)

4. Confirm patient adherence before declaring treatment failure 4

   • Non-compliance is a common reason for apparent treatment failure

5. In vulnerable populations (elderly), carefully weigh benefits of repeated eradication attempts against risks of repeated antibiotic exposure and high-dose acid suppression 4

6. Compile and utilize local antibiotic resistance data when available 4

   • Treatment selection should be informed by regional resistance patterns

Treatment Algorithm Summary

First attempt: Bismuth quadruple therapy × 14 days (or concomitant therapy in high clarithromycin resistance areas; triple therapy only if local clarithromycin resistance <15%) 1, 2

Second attempt: If bismuth quadruple therapy was first-line, use levofloxacin triple therapy × 14 days; if clarithromycin triple was first-line, use bismuth quadruple therapy × 14 days 1, 2, 3

Third attempt: Obtain susceptibility testing if available; otherwise use rifabutin triple therapy or high-dose dual therapy with antibiotics not previously used 4, 3

All regimens: Use high-dose PPI twice daily, extend duration to 14 days, and confirm eradication 4+ weeks post-treatment 1, 2