Vonoprazan Associated With Clostridioides difficile Infection, Comparable With PPI Use

Clostridioides difficile bacteria
Illustration of the bacteria Clostridioides difficile. These rod shaped bacteria have flagella, which are used for motility. Clostridioides difficile (formerly known as Clostridium difficile) are anaerobic bacteria prevalent in soil. In humans, the bacteria can become established in the colon and disrupt the normal gut microbiota, particularly in people taking antibiotics. Toxins released by Clostridioides difficile can produce diarrhoea and inflammation.
Researchers sought to evaluate the association of Clostridioides difficile infection onset in patients treated with vonoprazan.

Vonoprazan use is significantly associated with the onset of Clostridioides difficile infection (CDI), although the magnitude of the association is no greater than that for proton pump inhibitor (PPI) use, according to a study in the American Journal of Gastroenterology.

Researchers sought to evaluate the association of CDI onset in patients treated with vonoprazan in a retrospective case-control study. They utilized a hospital-based administrative database in Japan, which included medical and pharmacy claims data for inpatient and outpatient care.

All CDI cases from April 2014 to June 2019 were identified among patients aged >18 years at the time of disease onset. For each CDI case, 3 patients without CDI were included as controls. The study authors used conditional logistic regression analyses to estimate relative associations of gastric acid suppressants and other factors with CDI onset.

A total of 4466 patients with CDI were identified. Patients had a median age of 82 years (interquartile range [IQR], 73-88 years), and 51.5% were men. A control group included 13,220 patients without CDI (median age, 81 years; IQR, 73-87 years; 51.5% men).

Conditional regression analysis showed that previous antibiotic use was strongly associated with CDI in univariate and multivariate analyses with odds ratios (ORs) of 3.9 (95% CI, 3.6-4.3) and 3.9 ( 95% CI, 3.6-4.2), respectively. Regarding acid suppressants, PPI use was modestly, but significantly associated with CDI, with ORs of 1.3 (95% CI, 1.2-1.4) and 1.3 (95% CI, 1.2-1.4), using nonusers as a reference, respectively.

Vonoprazan use did not have significant intense associations with CDI onset compared with PPIs, with an OR of 1.07 (95% CI, 0.91-1.26), which remained when the participants were subdivided according to vonoprazan dose, with ORs of 1.12 (95% CI, 0.90-1.38) for 10 mg and 1.02 (95% CI, 0.81-1.29) for 20 mg.

According to the investigators, a major potential limitation of their findings may be the difficulty in adjusting the severity of a patient’s condition between cases and controls. Additionally, because CDI diagnosis was based on claims data, it may have been incomplete in some cases.

“Although vonoprazan possesses a more potent gastric acid inhibitory effect than PPIs in healthy volunteers, this study failed to show an additional increase in the association with the onset of CDI in patients treated with vonoprazan (relative to patients treated with PPIs),” stated the researchers. “Because all types of gastric acid suppressants could carry a risk of inducing CDI, as was demonstrated in this study, these drugs should be administered to patients with clinically appropriate indications,” they concluded.

Disclosure: One of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Watanabe K, Shimodaira Y, Takahashi S, et al. Potent acid suppression with vonoprazan vs proton pump inhibitors does not have higher association with Clostridioides difficile infection. Am J Gastroenterol. 2021;116(8):1632-1637. doi: 10.14309/ajg.0000000000001309