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

H. pylori Treatment

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

First-Line Treatment Selection

Bismuth quadruple therapy should be used as the default first-line regimen because:

• It achieves eradication rates of 80-90% even against metronidazole-resistant strains 1
• Bacterial resistance to bismuth is extremely rare 1
• It 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
• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective 1, 2

Alternative first-line regimens when bismuth is unavailable:

• Concomitant non-bismuth quadruple therapy: PPI twice daily + clarithromycin 500mg twice daily + amoxicillin 1000mg twice daily + metronidazole 500mg twice daily for 14 days 1, 3
• Rifabutin triple therapy: rifabutin 150mg twice daily + amoxicillin + PPI for 14 days (acceptable alternative, particularly for patients without penicillin allergy) 1, 2

In areas with documented low clarithromycin resistance (<15%):

• Triple therapy may be considered: PPI twice daily + clarithromycin 500mg twice daily + amoxicillin 1000mg twice daily for 14 days 1, 4, 3
• However, this should be abandoned in regions where clarithromycin resistance exceeds 15-20% 1, 4

Treatment Optimization

Critical factors for maximizing eradication success:

• Use high-dose PPI twice daily to reduce gastric acidity and enhance antibiotic activity, which increases efficacy by 6-10% compared to standard doses 1, 4
• Treat for 14 days rather than 7-10 days, as extending duration improves eradication success by approximately 5% 1, 4, 3
• Take medications at the start of a meal to minimize gastrointestinal intolerance 5
• Use higher doses of metronidazole (1.5-2g daily in divided doses) when combined with bismuth to improve eradication rates even with resistant strains 1

Second-Line Treatment After First-Line Failure

After failed first-line therapy, select an alternative regimen based on prior antibiotic exposure:

• If BQT was not used first-line: Use optimized BQT for 14 days 1, 2
• If BQT was used first-line: Use rifabutin triple therapy for 14 days 1, 2
• Levofloxacin-containing triple therapy (PPI twice daily + amoxicillin 1000mg twice daily + levofloxacin 500mg once daily or 250mg twice daily for 14 days) only if not previously used and in areas with low levofloxacin resistance 1, 4

Critical caveat: Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates and FDA warnings about serious side effects 1

Salvage Therapy After Multiple Failures

After two failed eradication attempts:

• Antibiotic susceptibility testing is strongly recommended to guide further treatment 1, 4, 2
• If susceptibility testing is unavailable, use antibiotics not previously used or for which resistance is unlikely (amoxicillin, tetracycline, bismuth, or furazolidone) 3
• High-dose dual therapy with amoxicillin and PPI is an alternative rescue option 1

Common Pitfalls to Avoid

Do not repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as this maximizes the probability of treatment failure 1, 6

Do not use inadequate PPI dosing (once daily or low dose), as this significantly reduces treatment efficacy 4, 6

Do not prescribe treatment for only 7-10 days, as this is a common error that reduces eradication rates 6

For patients with reported penicillin allergy: Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare and it is a highly effective component of therapy 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, 3

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test:

• At least 4 weeks after completion of therapy 1, 4
• At least 2 weeks after PPI discontinuation 1, 4
• Do not use serology to confirm eradication, as antibodies may persist long after successful treatment 4