Potent Acid Suppression With Vonoprazan vs Proton Pump Inhibitors Does Not Have Higher Association With Clostridioides difficile Infection

Am J Gastroenterol. 2021 Aug 1;116(8):1632-1637. doi: 10.14309/ajg.0000000000001309.


Introduction: Proton pump inhibitors (PPIs) are associated with the onset of Clostridioides difficile infection (CDI). Although a new potassium-competitive acid blocker, vonoprazan, consistently shows a more potent acid inhibitory effect in comparison to PPIs, the risk of CDI in vonoprazan-treated patients relative to those treated with PPIs is unknown. In this retrospective case-control study, using a nationwide hospital-based administrative database in Japan, we investigated the association of the onset of CDI in patients treated with vonoprazan.

Methods: A CDI case was defined as a case in which a patient was diagnosed and treated for CDI. For each CDI case, 3 non-CDI patients were extracted as controls. Information on the usage of acid suppressants in the 2 months before the onset of CDI and other confounding factors was collected. Relative associations of gastric acid suppressants with the onset of CDI were estimated.

Results: A total of 4,466 CDI cases and 13,220 of non-CDI controls were extracted. A multivariate conditional regression analysis revealed that PPI or vonoprazan use was modestly, but significantly associated with CDI (odds ratio [95% confidence interval]: PPI, 1.3 [1.2-1.4]; vonoprazan, 1.4 [1.2-1.7]). With PPI users as a reference, vonoprazan did not show a stronger association with CDI (odds ratio [95% confidence interval]: 1.07 [0.91-1.26]).

Discussion: We found a significant positive association between vonoprazan use and CDI; however, the magnitude of the association was not beyond that in PPI users. This is the first report on any potential adverse effects of vonoprazan.

MeSH terms

  • Aged
  • Case-Control Studies
  • Clostridium Infections / epidemiology*
  • Female
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / adverse effects*
  • Pyrroles / adverse effects*
  • Retrospective Studies
  • Sulfonamides / adverse effects*


  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Proton Pump Inhibitors
  • Pyrroles
  • Sulfonamides