What is the recommended treatment for a patient with a positive H. pylori (Helicobacter pylori) breath test and normal Complete Blood Count (CBC) results?

Treatment of H. pylori Infection with Positive Breath Test

Initiate a 14-day course of bismuth quadruple therapy (BQT) as first-line treatment, consisting of a proton pump inhibitor (PPI), bismuth subsalicylate, metronidazole, and tetracycline. 1

First-Line Treatment Regimen

The 2024 American College of Gastroenterology guideline establishes BQT for 14 days as the preferred empiric regimen when antibiotic susceptibility is unknown. 1 This recommendation supersedes older approaches and reflects current antibiotic resistance patterns in North America.

Alternative first-line options if BQT is unavailable or contraindicated include: 1

• PPI-based triple therapy: PPI plus clarithromycin (500 mg) plus amoxicillin (1 g), both twice daily for 14 days 2
• Rifabutin triple therapy for 14 days (suitable empiric alternative in patients without penicillin allergy) 1

The standard triple therapy achieves eradication rates near 90% when used for 10-14 days, though this has declined due to rising clarithromycin resistance. 2 For patients with penicillin allergy, substitute metronidazole (500 mg twice daily) for amoxicillin. 2

Critical Treatment Principles

Duration matters: 14-day regimens are superior to shorter courses. 1 The older recommendation of 10 days has been replaced by 14-day treatment to improve eradication rates. 2, 1

PPI dosing: Full-dose PPI therapy (e.g., omeprazole 20 mg once daily or equivalent) should be used for optimal acid suppression and antibiotic efficacy. 3 PPIs should be taken at the start of meals to minimize gastrointestinal intolerance. 3

Post-Treatment Confirmation of Eradication

Mandatory follow-up testing is required to confirm H. pylori eradication, regardless of symptom resolution. 4, 3 This is particularly critical given that:

• H. pylori infection always implies gastritis, a risk factor for peptic ulcer disease and gastric cancer 4
• Treatment failure occurs in 10-20% of cases even with optimal regimens 2

Timing and test selection for confirmation: 4, 3

• Wait at least 4 weeks after completing antibiotic therapy before testing
• Stop PPIs for at least 2 weeks before testing to avoid false-negative results 3
• Use either 13C-urea breath test (preferred, sensitivity/specificity >90%) 2, 5 or stool antigen test (sensitivity/specificity 90-95%) 3, 5
• Never use serology for post-treatment confirmation, as antibodies remain elevated after eradication 2

Management of Treatment Failure

If follow-up testing remains positive, the patient has refractory H. pylori infection. 2 Before prescribing alternative antibiotics, identify contributing factors: 2

• Confirm medication adherence during initial treatment
• Review antibiotic history to avoid repeating previously used agents
• Consider antibiotic susceptibility testing if available 2

For first treatment failure (after initial BQT): 1

• If not previously treated with optimized BQT, retry optimized BQT for 14 days
• If previously treated with optimized BQT, use rifabutin triple therapy for 14 days

Avoid clarithromycin or levofloxacin in salvage regimens unless antibiotic susceptibility is confirmed, as resistance rates are high (clarithromycin resistance increases treatment failure 7-fold, levofloxacin 8.2-fold). 2

Important Clinical Caveats

Patient adherence is critical: The multidrug nature and duration of therapy are associated with decreased compliance, leading to treatment failure. 2 Counsel patients on the importance of completing the full 14-day course despite potential side effects.

Antibiotic resistance considerations: 2

• Clarithromycin resistance rates have risen to 9-35% in North America
• Prior antibiotic exposure (even for unrelated infections) increases resistance risk
• Selecting therapy based on prior antibiotic exposure is non-inferior to susceptibility testing 2

Do not use monotherapy: Single-antibiotic regimens increase resistance and should never be used. 4

Normal CBC does not change management: The presence of normal hemoglobin and hematocrit simply excludes active bleeding or anemia as complications; it does not alter the indication for or choice of eradication therapy. 4

Dietary Modifications

While dietary modifications are commonly recommended, the evidence supporting specific dietary changes for H. pylori eradication is limited. Focus should remain on medication adherence rather than dietary restrictions during treatment.