How does proton pump inhibitor (PPI) therapy affect Helicobacter pylori (H. pylori) testing?

H. pylori Testing While on PPI

Stop PPIs for at least 2 weeks before performing H. pylori testing with urea breath test, stool antigen test, or biopsy-based methods (rapid urease test, histology, culture) to avoid false-negative results. 1

Impact of PPIs on Test Accuracy

PPIs significantly interfere with H. pylori diagnostic testing by increasing gastric pH, which decreases bacterial load—particularly in the antrum—leading to 10-40% false-negative rates across most testing modalities. 1

Tests Affected by PPIs:

• Urea breath test (UBT): Most extensively studied, showing substantial false-negative rates 1
• Stool antigen test (SAT): Similarly affected by reduced bacterial load 1
• Rapid urease test: Sensitivity significantly reduced, especially at 1 hour 2
• Histology: Controversial—specialized pathologists may still diagnose based on inflammatory patterns even without visible organisms, but many pathologists cannot 1
• Culture: Reduced bacterial yield 1

Test NOT Affected by PPIs:

• IgG serology: Antibodies remain elevated for months to years regardless of bacterial load changes, making this the only reliable test during PPI therapy 1

Recommended Testing Strategy

If PPIs Can Be Stopped:

Discontinue PPIs for 2 weeks before testing to allow bacterial repopulation of the stomach, then proceed with UBT or stool antigen test. 1 Note that in vitro data suggests complete bacterial recovery may require up to 12 days. 3

Key timing requirements before testing:

• PPIs: Stop ≥2 weeks (some sources suggest ≥7 days minimum) 1
• Antibiotics and bismuth: Stop ≥4 weeks 1
• Fasting: ≥6 hours before UBT 1

If PPIs Cannot Be Stopped:

Use validated IgG serology (laboratory-based ELISA with >90% accuracy, not office-based rapid tests). 1, 4 This is particularly appropriate when:

• Patient requires continuous acid suppression for symptom control 4
• Very high pretest probability exists (e.g., active duodenal ulcer) 1
• Recent ulcer bleeding, atrophic gastritis, or gastric malignancy present 1

Critical Caveats

Serology limitations:

• Cannot distinguish active infection from past infection (remains positive after eradication) 1
• Should NOT be used to confirm eradication after treatment 1
• Requires confirmation with active infection test (UBT or SAT) before treatment if pretest probability is not very high 1

False-positive considerations:

• Achlorhydria (pernicious anemia, atrophic gastritis) can cause false-positive UBT due to urease-producing non-H. pylori organisms 1
• If repeated treatment failures occur, confirm positive UBT with stool antigen test or endoscopy before additional therapy 1

Important note on H2-receptor antagonists:

• Famotidine and other H2-blockers cause fewer false-negatives than PPIs and can be substituted during the washout period 1, 4

Positive Test Interpretation

A positive result on any test (UBT, SAT, biopsy-based) can be trusted even during PPI use, as PPIs reduce bacterial load but do not cause false-positives. 1 Only negative results are unreliable during PPI therapy. If doubt exists about a negative result, repeat testing after appropriate washout period (≥2 weeks). 1