What is the recommended test of cure for a patient who has completed eradication therapy for Helicobacter pylori (H. pylori) infection?

Test of Cure for H. pylori After Eradication Therapy

Perform a urea breath test (UBT) or validated monoclonal stool antigen test at least 4 weeks after completing H. pylori eradication therapy to confirm successful eradication. 1, 2

Recommended Testing Methods

Use non-invasive tests that detect active infection—never use serology for test of cure. 3, 1

First-Line Options (Non-Invasive)

• Urea breath test (UBT): Sensitivity 94.7-97%, specificity 95-100%, considered the gold standard for confirmation testing 3, 1
• Monoclonal stool antigen test: Sensitivity and specificity >90%, equally accurate alternative to UBT 3, 1

When to Use Invasive Testing

• Endoscopy with biopsy is indicated when clinically necessary, particularly for gastric ulcers (to confirm healing), gastric MALT lymphoma, or complicated peptic ulcer disease 1, 2

What NOT to Use

• Serology has no role in determining eradication success because antibody levels remain elevated after H. pylori elimination and cannot distinguish active from past infection 3, 1

Critical Timing Requirements

Wait a minimum of 4 weeks after treatment completion before testing. 1, 2 Testing earlier yields false-negative results because:

• The gastric mucosa requires adequate recovery time 1, 2
• Temporary bacterial suppression can mimic true eradication 1, 2

Special Timing Considerations

• For bleeding peptic ulcers: Delay testing to 4-8 weeks after the bleeding episode 1, 2

Mandatory Medication Washout Before Testing

To avoid false-negative results, ensure proper medication discontinuation:

• Proton pump inhibitors (PPIs): Stop for at least 2 weeks, preferably 7-14 days 3, 2
• Antibiotics and bismuth: Discontinue for at least 4 weeks 3, 2
• Fasting: Patients should fast for at least 6 hours before UBT 3

Who Requires Mandatory Test of Cure

Confirmation testing is now considered standard of care for all treated patients. 1 However, it is absolutely mandatory in these high-risk scenarios:

• Complicated peptic ulcer disease (including bleeding ulcers) 1, 2
• All gastric ulcers (requires endoscopic follow-up to ensure complete healing) 1, 2
• Low-grade gastric MALT lymphoma 1, 2
• Cases with poor compliance or low treatment efficacy 1, 2

When Testing May Be Optional

• Uncomplicated duodenal ulcer with complete symptom resolution 2
• Non-ulcer dyspepsia with symptom resolution 2

However, the controversy about routine retesting has largely been resolved—current consensus favors confirmation testing in all cases. 3, 1

Management Based on Test Results

If Eradication is Confirmed

• Uncomplicated duodenal ulcer: Discontinue PPI therapy 2
• Gastric ulcer: Continue PPI until complete healing is confirmed by endoscopy 2
• Complicated duodenal ulcer or bleeding ulcer: Continue PPI until eradication is confirmed 2

If H. pylori Persists After Initial Treatment

• Use a completely different antibiotic regimen—never repeat the same failed regimen 1, 2
• Avoid antibiotics used previously, particularly clarithromycin or levofloxacin if there is history of macrolide or fluoroquinolone exposure 1
• Second-line options: 14-day levofloxacin triple therapy or 14-day bismuth quadruple therapy (if not used initially) 1, 4
• After two treatment failures: Pursue antimicrobial susceptibility testing to guide third-line therapy 1, 2, 5

Common Pitfalls and How to Avoid Them

Testing Too Early

• Pitfall: Testing before 4 weeks yields unreliable results due to temporary bacterial suppression rather than true eradication 1, 2
• Solution: Always wait the full 4 weeks (or 4-8 weeks for bleeding ulcers) 1, 2

Inadequate PPI Washout

• Pitfall: False-negative results occur if PPIs are not stopped for sufficient duration 2
• Solution: Discontinue PPIs for at least 2 weeks before testing; if this is not feasible, use the monoclonal stool antigen test which is less affected by PPI use 1

Using Serology for Test of Cure

• Pitfall: Serology cannot distinguish active infection from past exposure 3, 1
• Solution: Only use tests for active infection (UBT or stool antigen) 3, 1

Repeating the Same Failed Regimen

• Pitfall: Simply repeating the same regimen after treatment failure leads to further resistance and treatment failure 1, 2
• Solution: Always use a completely different antibiotic combination, avoiding previously used antibiotics 1, 2

Ignoring Compliance Issues

• Pitfall: Treatment failure is often due to poor medication adherence rather than antibiotic resistance 1
• Solution: Before prescribing retreatment, address adherence barriers by explaining the rationale, dosing, expected side effects, and importance of completing the full course 1

Clinical Significance of Confirmation Testing

Confirming eradication provides an indirect measure of antibiotic resistance/susceptibility in the population and prevents ulcer recurrence and complications. 3, 1 Persistent H. pylori infection after treatment is a negative prognostic marker for:

• Ulcer recurrence 1
• Risk of ulcer complications including rebleeding (26% rebleeding rate without eradication) 3
• Treatment failure in MALT lymphoma cases 1