Vonoprazan, Proton Pump Inhibitors Associated With Increased Risk of CDI

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The investigators also found that PPIs and vonoprazan had equivalent magnitudes of association with CDI in the matched subgroup.

A new analysis show some common hospital treatments are linked to an increased risk of developing clostridiodes difficile infections (CDI).1

A team, led by Yohei Saruta, Department of Gastroenterology, Akita University Graduate School of Medicine, evaluated the association between several classes of acid suppressants and CDI, particularly for the differences in the magnitudes of association between proton pump inhibitors (PPI) and vonoprazan.

Medicine and CDI

PPI use has long been associated with an increased risk of developing CDI, as well as a leading cause of nosocomial diarrhea.

However, there have been limited research into the association between vonoprazan, a novel potassium-competitive acid blocker, and CDI, but there have been no studies conducted in a clinical setting.

In the retrospective hospital-based cohort from a secondary-care hospital in Japan, the (n = 25,821) investigators collected data on 91 individuals with hospital-onset cases of CDI.

Analyzing the Data

The team conducted a multivariable adjusted logistic regression analysis for the entire cohort and a propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n = 10,306).

The results show an incidence rate of 1.42 cases of CDI per 10,000 patient days. This is comparable to previous research.

The multivariable analysis showed that PPIs were positively associated with CDI (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.67-5.96), as were vonoprazan (OR, 2.63; 95% CI, 1.01-6.88).

The investigators also found that PPIs and vonoprazan had equivalent magnitudes of association with CDI in the matched subgroup analyses.

“We found that both PPIs and vonoprazan were associated with CDI, and the magnitude of the association was comparable,” the authors wrote. “Since vonoprazan is widely available in Asian countries, further studies on the association of its usage with CDI are warranted.”

PPI and Infections

Earlier this year, investigators found PPI use was associated with an increased risk of drug-resistant infections.

In the past, PPI has been linked to an increased risk of colonization with drug-resistant bacteria. However, there is some doubt about this association, largely because of possible confounding by lifestyle-associated factors and disease severity. In addition, whether this risk is dose dependent is not currently known.

A team, led by Roel P. J. Willems, MD, Department of Medical Microbiology and Infection Prevention, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, Academic Medical Center, assessed the association between PPI treatment and the risk of acquiring drug-resistant Enterobacterales and examined the interactions with possible microbiome-altering agents.

The investigators estimated the adjusted incidence rate ratios (AIRRs) of ESBL- or carbapenemase-producing Enterobacterales acquisition by PPI dose and time risk windows using conditional logistic regression models.

These were estimated for 30 days for the primary outcome and 90 days for the secondary outcome.

The results show an aIRR of 1.48 (95% confidence interval [CI], 1.15-1.91) for PPI use overall at 30 days. After conducting a sensitivity analysis and an analysis of the pair-matched study with prospectively enrolled patients (aIRR, 2.96; 95% CI, 1.14-7.74), the investigators found similar results.


Saruta, Y., Watanabe, K., Tsuji, T., Takahashi, Y., Matsuzawa, H., Yoshida, T., Takahashi, S., Shimodaira, Y., Matsuhashi, T., & Iijima, K. (2023). Vonoprazan poses no additional risk of developing clostridioides difficile infection compared to proton pump inhibitors. Journal of Gastroenterology and Hepatology.