Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth, Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study

Helicobacter. 2016 Apr;21(2):143-52. doi: 10.1111/hel.12246. Epub 2015 Jul 28.


Background: Proton-pump inhibitor (PPI) consumption does lead to false-negative results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid urease test (RUT).

Materials and methods: Helicobacter pylori isolates from 112 dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The effect of a sublethal concentration of OMP on bacterial features and their recovery after removal of OMP was also assessed.

Results: Of 112 culture-positive gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a significant correlation between negative RUT results and PPI consumption (p < .05). OMP (minimum inhibitory concentration, MIC 32 μg/mL) and LPZ (MIC 8 μg/mL) inhibited the growth of 78.6% of H. pylori isolates. OMP and LPZ inhibited urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between 20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease. Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar (BBA) supplemented with OMP resulted in reduced bacterial viability (1+), compared with control (4+), change of spiral morphology to coccoid, and reduction in pink color intensity in urea agar. Bacterial growth (1+), morphology, and urease test did not improve after the first 3-day and second 3-day (6 days) subcultures on BBA. However, relative recovery occurred after the third 3-day (9 days) subculture and complete recovery was observed after the fourth 3-day (12 days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease test.

Conclusion: Proton-pump Inhibitors exert transient negative effects on H. pylori viability, morphology, and urease test. Accordingly, cessation of PPI consumption at least 12 days before endoscopy could help avoiding false-negative results of H. pylori diagnostic tests.

Keywords: Helicobacter pylori; PPIs; growth; morphology; negative effect; urease.

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacology
  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology*
  • Female
  • Helicobacter pylori / cytology
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / enzymology*
  • Helicobacter pylori / physiology
  • Humans
  • Lansoprazole / pharmacology
  • Male
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Middle Aged
  • Omeprazole / pharmacology
  • Pantoprazole
  • Proton Pump Inhibitors / pharmacology*
  • Urease / analysis*
  • Young Adult


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Lansoprazole
  • Pantoprazole
  • Urease
  • Omeprazole