H. pylori Treatment Recommendations
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
First-Line Treatment Regimen
The optimal first-line regimen is bismuth quadruple therapy for 14 days, which achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance. 1 This regimen includes:
- Proton pump inhibitor (PPI): 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 HCl: 500 mg four times daily 1, 2
Critical administration details: Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids. 1 Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance. 3
Do not use doxycycline as a substitute for tetracycline HCl, as doxycycline is ineffective for H. pylori eradication despite being a tetracycline derivative. 2
Why Bismuth Quadruple Therapy is Preferred
The superiority of bismuth quadruple therapy stems from several key factors:
- No bacterial resistance to bismuth has been described, making it effective even against multidrug-resistant strains 1
- Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, rendering traditional triple therapy unacceptably ineffective with only 70% eradication rates 1
- Bismuth's synergistic effect overcomes metronidazole resistance, allowing successful eradication even with resistant strains 1
- 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 When Bismuth is Unavailable
If bismuth is not available, use concomitant non-bismuth quadruple therapy for 14 days: 1
- PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
- Amoxicillin 1000 mg twice daily 1
- Clarithromycin 500 mg twice daily 1
- Metronidazole 500 mg twice daily 1
Critical caveat: Avoid this regimen if the patient has had previous macrolide exposure for any indication, as cross-resistance is universal within the macrolide family. 1
FDA-Approved Alternative Regimens
The FDA approves two specific regimens for H. pylori in adults: 3
Triple therapy: 1 gram amoxicillin + 500 mg clarithromycin + 30 mg lansoprazole, all given twice daily for 14 days 3
Dual therapy: 1 gram amoxicillin + 30 mg lansoprazole, each given three times daily for 14 days (for patients allergic or intolerant to clarithromycin, or when clarithromycin resistance is known or suspected) 3
However, these FDA-approved regimens are now considered suboptimal due to rising clarithromycin resistance rates exceeding 15% in most regions. 1
Second-Line Treatment After First-Line Failure
After bismuth quadruple therapy failure, use levofloxacin triple therapy for 14 days (if no prior fluoroquinolone exposure): 1
- PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
- Amoxicillin 1000 mg twice daily 1
- Levofloxacin 500 mg once daily or 250 mg twice daily 1
Critical warning: 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 due to rapidly rising fluoroquinolone resistance rates (11-30% primary, 19-30% secondary). 1
Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1
If susceptibility testing is unavailable, consider:
Rifabutin triple therapy for 14 days: 1
- Rifabutin 150 mg twice daily 1
- Amoxicillin 1000 mg twice daily 1
- PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
High-dose dual amoxicillin-PPI therapy for 14 days (alternative rescue option): 1
Critical Optimization Factors
Treatment duration of 14 days is mandatory, as it improves eradication success by approximately 5% compared to 7-10 day regimens. 1
High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate and significantly reduces treatment efficacy. 1 Esomeprazole 40 mg twice daily is strongly preferred over standard 20 mg dosing. 1
Higher doses of metronidazole (1.5-2 g daily in divided doses) improve eradication rates even with resistant strains when combined with bismuth. 1
Special Populations
In patients with penicillin allergy, bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 1
Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare (<5%). 1
In pediatric patients, treatment should only be conducted by pediatricians in specialist centers. 1
In patients with severe renal impairment (GFR <30 mL/min), do NOT use the 875 mg amoxicillin dose. 3 For GFR 10-30 mL/min, use 500 mg or 250 mg every 12 hours; for GFR <10 mL/min, use 500 mg or 250 mg every 24 hours. 3
Confirmation 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
Managing 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, though evidence for increasing eradication rates is limited. 1, 4
Patient Factors Affecting Success
Smoking increases the risk of eradication failure (odds ratio 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, leading to much lower eradication rates. 1
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. 1
Do not use concomitant, sequential, or hybrid therapies—they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit. 1
Standard-dose PPI once daily is inadequate—always use twice-daily dosing to maximize gastric pH elevation. 1