Treatment of H. pylori Infection
Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in most clinical settings, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1
First-Line Treatment Selection
Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it the most reliable empiric choice when antibiotic susceptibility is unknown. 1 This regimen includes:
- Proton pump inhibitor (PPI): Standard dose twice daily, taken 30 minutes before meals 1
- Bismuth subsalicylate: 262 mg four times daily (or bismuth subcitrate 120 mg 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, not 7-10 days) 1
The superiority of bismuth quadruple therapy stems from the fact that no bacterial resistance to bismuth has been described, and bismuth's synergistic effect overcomes metronidazole resistance that exists in vitro. 1 Additionally, tetracycline resistance remains rare globally. 1
Alternative First-Line Option in Low Clarithromycin Resistance Areas
In regions where clarithromycin resistance is documented to be less than 15%, triple therapy may be considered: 1
- PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days 1
However, this regimen should be abandoned in most of North America and Europe where clarithromycin resistance now exceeds 15-20%. 1 When H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to approximately 20%. 1
When Bismuth is Unavailable
Concomitant non-bismuth quadruple therapy is the recommended alternative when bismuth products are not accessible: 1
- PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days 1
This regimen administers all antibiotics simultaneously, preventing resistance development during treatment. 1
Critical Optimization Factors
PPI Dosing
High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate. 1 Using high-dose PPI increases cure rates by 6-10% compared to standard dosing. 1
Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by an additional 8-12% compared to other PPIs. 1 The PPI must be taken 30 minutes before meals on an empty stomach, without concomitant use of other antacids. 1
Treatment Duration
14 days of treatment is superior to 7-10 day regimens, improving eradication success by approximately 5%. 1 This is non-negotiable for maximizing first-attempt success. 2
Antibiotic Selection Principles
Never repeat antibiotics that have failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1 However, metronidazole can be re-used with bismuth because bismuth's synergistic effect overcomes resistance, and amoxicillin and tetracycline can be re-used because resistance to these agents remains rare. 1
Second-Line Treatment After First-Line Failure
If Bismuth Quadruple Therapy Was Not Used First-Line
Bismuth quadruple therapy for 14 days is the preferred second-line option. 1
If Bismuth Quadruple Therapy Has Already Failed
Levofloxacin-based triple therapy for 14 days is recommended if the patient has no prior fluoroquinolone exposure: 1
- PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) for 14 days 1
Important caveat: Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary), and the FDA recommends fluoroquinolones be used as a last choice due to risk of serious side effects. 1 Do not use levofloxacin empirically as first-line therapy. 1
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient compliance, antibiotic susceptibility testing should guide further treatment. 1, 2 When susceptibility testing is unavailable or while awaiting results:
Rifabutin-Based Triple Therapy
Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily for 14 days is highly effective as rescue therapy. 1 Rifabutin resistance is extremely rare, making this an excellent salvage option. 1
High-Dose Dual Therapy
Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily for 14 days is an alternative rescue therapy when other options have been exhausted. 1
Special Populations
Penicillin Allergy
Bismuth quadruple therapy is the first choice in patients with penicillin allergy, as it contains tetracycline, not amoxicillin. 1 If bismuth is unavailable, triple therapy with PPI + clarithromycin + metronidazole may be used, though this has lower efficacy. 1
Pediatric Patients
Treatment of H. pylori infection in pediatric patients 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
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
Never use serology to confirm eradication—antibodies may persist long after successful treatment. 1
Adjunctive Therapies
Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance. 1 Diarrhea occurs in 21-41% of patients during the first week of eradication therapy due to disruption of normal gut microbiota. 1 However, probiotics should not be considered primary treatment and have no solid evidence to increase eradication rates. 1
Common Pitfalls to Avoid
Using standard triple therapy in areas with clarithromycin resistance >15%: This is the most common error, occurring in 46% of cases in European registries. 3 Clarithromycin resistance has increased globally from 9% in 1998 to 17.6% in 2008-2009. 1
Prescribing treatment for only 7-10 days: This occurred in 69% of cases in European practice but significantly reduces eradication rates. 3
Using low-dose or once-daily PPI: This occurred in 48% of cases but is a critical error that substantially reduces efficacy. 3
Repeating failed antibiotics: More than 15% of practitioners repeat antibiotics after eradication failure, which is futile for clarithromycin and levofloxacin. 3
Not checking eradication success: 6% of practitioners fail to confirm eradication, missing treatment failures. 3
Assuming penicillin allergy without verification: Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare. 1
Patient Factors Affecting Success
Smoking increases the risk of eradication failure with an odds ratio of 1.95 for smokers versus non-smokers. 1 High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level. 1 Poor compliance affects more than 10% of patients and leads to much lower eradication rates. 1