What is the recommended treatment for H pylori (Helicobacter pylori) infection?

H. pylori Treatment

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

First-Line Treatment Selection

Preferred Regimen: Bismuth Quadruple Therapy

• Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to the synergistic effect of bismuth with other antibiotics. 3
• The regimen consists of: PPI twice daily + bismuth subsalicylate + metronidazole + tetracycline HCl for 14 days 1, 2
• Bismuth is valuable because bacterial resistance to this compound is extremely rare, making this regimen effective even in areas with high antibiotic resistance 1, 2, 3
• This approach 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 3

Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy

• When bismuth is unavailable, use concomitant therapy: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days 2, 3
• This regimen is only appropriate in areas where clarithromycin resistance is <15%, which now excludes most of North America and Central, Western, and Southern Europe where resistance exceeds 20% 3
• Do not use sequential therapy—all antibiotics must be given simultaneously to prevent resistance development during treatment. 3

Why Traditional Triple Therapy Should Be Abandoned

• Standard triple therapy (PPI + clarithromycin + amoxicillin) should be abandoned when regional clarithromycin resistance exceeds 15-20% 2, 3
• Clarithromycin resistance has increased globally from 9% in 1998 to 17.6% in 2008-2009, and now exceeds 20% in most regions 4, 3
• When H. pylori strains are clarithromycin-resistant, eradication rates drop to approximately 20% compared to 90% with susceptible strains 3

Optimizing Treatment Success

PPI Dosing

• Always use high-dose PPI twice daily—this increases eradication efficacy by 6-10% compared to standard doses by reducing gastric acidity and enhancing antibiotic activity. 1, 2
• Standard-dose PPI once daily is inadequate 3
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% 4

Treatment Duration

• 14-day duration is preferred over shorter regimens to maximize eradication rates. 1, 2
• Extending treatment duration from 7 to 14 days improves eradication success by approximately 5% 4, 2

Medication Administration

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

Second-Line Treatment After First-Line Failure

After Clarithromycin-Containing Therapy Fails

• Use bismuth quadruple therapy (if not previously used) for 14 days 4, 1
• Alternative: Levofloxacin triple therapy (PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily or 250 mg twice daily) for 14 days 4, 2
• Rising rates of levofloxacin resistance (11-30% primary, 19-30% secondary) should be taken into account—do not use levofloxacin empirically as first-line therapy. 4, 3

After Bismuth Quadruple Therapy Fails

• Levofloxacin-containing triple therapy is recommended in areas of high clarithromycin resistance 4

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts

• Antimicrobial susceptibility testing should guide further treatment whenever possible. 1, 2
• When susceptibility testing is not available, use antibiotics not previously used or for which resistance is unlikely: amoxicillin, tetracycline, bismuth, or furazolidone 6

Rifabutin-Based Therapy

• Rifabutin triple therapy (rifabutin 150 mg twice daily + amoxicillin + PPI) for 14 days is effective for persistent infection after previous treatment failures 1, 3
• Rifabutin has the advantage of rare bacterial resistance 1
• Rifabutin should be reserved for patients who have failed previous eradication attempts—it is not recommended as first-line therapy. 3

High-Dose Dual Therapy

• High-dose dual amoxicillin-PPI therapy is an alternative rescue option 2

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
• Serology should not be used to confirm eradication as antibodies may persist long after successful treatment 1, 2

Critical Pitfalls and Caveats

Antibiotic Selection Errors

• Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin. 1, 2, 3
• If the patient has had prior macrolide exposure for any indication, avoid clarithromycin as cross-resistance is universal within the macrolide family 3
• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 3

PPI Dosing Errors

• Inadequate PPI dosing significantly reduces H. pylori treatment efficacy 1, 2
• Confirm that patients are taking the PPI correctly to maximize absorption and activation 1

Special Populations

• In patients allergic to penicillin, amoxicillin can be replaced with tetracycline or metronidazole 2, 6
• Do not assume penicillin allergy without verification—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 3
• In children, fluoroquinolones and tetracyclines should not be used 2
• Patients with renal impairment (GFR <30 mL/min) should not receive the 875 mg amoxicillin dose 5

Patient Factors Affecting Success

• Smoking is a risk factor for failure, with an odds ratio of 1.95 for eradication failure among smokers versus non-smokers 4
• High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level 4

Side Effect Management

• Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota 3
• Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance 3, 6