Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors

Am J Gastroenterol. 2003 May;98(5):1005-9. doi: 10.1111/j.1572-0241.2003.07426.x.


Objective: The mechanism of false negative urea breath tests (UBTs) results among proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI-associated negative UBT, the relation to Helicobacter pylori density, and whether gastric acidification would prevent false negative UBT results.

Method: In the UBT experiment, H. pylori-infected volunteers received omeprazole 20 mg b.i.d. for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and 1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment, after a wash-out of >5 months, nine of the original subjects were rechallenged with omeprazole for 6.5 days. Antral and corpus biopsies for histology and culture were done before and 1 day after PPI administration.

Results: Thirty subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day 6.5 (p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT recovered in all but one subject by the fourth day post-PPI and in all subjects by day 14. In the culture and histology experiment, upon PPI rechallenge, three of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by culture or histology, decreased with PPI therapy; antral biopsies became histologically negative in five subjects and corpus biopsies in three subjects.

Conclusion: PPI-induced negative UBT results were related to the anti-H. pylori effect of the PPI. Acidification of the stomach did not prevent false negative UBT results. Three days is likely the minimum delay from stopping PPI until one should perform a test for active infection. A delay of 14 days is preferred.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-Ulcer Agents / therapeutic use*
  • Breath Tests / methods
  • Carbon Radioisotopes
  • False Negative Reactions
  • Female
  • Helicobacter Infections / diagnosis*
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / isolation & purification*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Omeprazole / therapeutic use*
  • Proton Pump Inhibitors
  • Statistics, Nonparametric
  • Stomach / microbiology
  • Stomach / pathology
  • Time Factors
  • Urea*


  • Anti-Ulcer Agents
  • Carbon Radioisotopes
  • Proton Pump Inhibitors
  • Urea
  • Omeprazole