Can you treat for Helicobacter pylori (H. pylori) if the breath test is negative, possibly due to Proton Pump Inhibitor (PPI) use?

Do Not Treat Based on a Negative Breath Test While on PPIs

You should not treat for H. pylori based on a negative breath test if the patient was taking PPIs at the time of testing, as this represents a false-negative result in 10-40% of cases. 1

Why PPIs Cause False-Negative Results

PPIs increase gastric pH, which decreases H. pylori bacterial load, especially in the antrum, leading to false-negative results on urea breath tests (UBT), stool antigen tests (SAT), rapid urease tests, histology, and culture. 1 The mechanism is suppression of bacterial density rather than true eradication. 2

• Serology is the only test unaffected by PPIs because H. pylori antibodies remain present for months after bacterial suppression. 1
• Studies demonstrate that 33% of H. pylori-infected patients develop transient negative UBTs while on PPI therapy. 2
• The false-negative rate ranges from 10-40% across most diagnostic modalities during PPI use. 1

Correct Testing Strategy

Stop PPIs for at least 2 weeks before retesting to allow bacteria to repopulate the stomach, which restores test accuracy. 1, 3

• A 14-day washout period is the minimum recommended interval. 2
• After stopping PPIs, previously negative tests (UBT, SAT, rapid urease test, histology, culture) can become positive again. 1
• No studies have evaluated the necessary washout period after long-term PPI treatment, so longer delays may be prudent in chronic PPI users. 1

If stopping PPIs is not possible due to symptom management needs, use validated IgG serology instead, as it is not affected by acid suppression. 1, 3

• Only use validated commercial serological tests with >90% sensitivity and specificity. 3
• Avoid rapid in-office serological tests due to limited accuracy. 3

Clinical Algorithm

1. Patient on PPIs with negative breath test: Do not treat based on this result alone
2. Stop PPIs for 2 weeks minimum (14 days preferred, longer if chronic use)
3. Retest with UBT or stool antigen test after washout period
4. If PPI discontinuation is not feasible: Use validated IgG serology (>90% accuracy)
5. Treat only if confirmatory testing is positive

Important Caveats

• A positive test result during PPI use can be trusted - PPIs cause false-negatives, not false-positives. 4
• H2-receptor antagonists (like famotidine) also cause false-negatives but to a much lesser extent than PPIs, and the guidelines did not find it necessary to stop them before testing if using citric acid. 1
• The clinical consequences of treating based on a false-negative test include missing true H. pylori infection, which increases long-term gastric cancer risk. 4