Vonoprazan poses no additional risk of developing Clostridioides difficile infection compared to proton pump inhibitors

Abstract

Background and Aim The use of proton pump inhibitors (PPIs) has been repeatedly reported as a trigger of Clostridioides difficile infection (CDI), a leading cause of nosocomial diarrhea. However, only a few studies have reported on the association between vonoprazan, a novel potassium‐competitive acid blocker providing potent acid suppression, and CDI, with no studies having been conducted in a clinical setting. We therefore evaluated the association between various classes of acid suppressants and CDI with special attention paid to differences in the magnitudes of association between PPIs and vonoprazan. Methods A retrospective hospital‐based cohort from a secondary‐care hospital in Japan (n = 25 821) was collected, wherein eligible CDI cases were defined as hospital‐onset cases (n = 91). A multivariable adjusted logistic regression analysis for the entire cohort and propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n = 10 306) were performed. Results The overall CDI incidence rate was 1.42/10 000 patient‐days, which was comparable with previous reports. A multivariable analysis showed that both PPIs and vonoprazan were positively associated with CDI (odds ratios [95% confidence intervals]: 3.15 [1.67–5.96] and 2.63 [1.01–6.88], respectively). In addition, matched subgroup analyses showed that PPIs and vonoprazan had equivalent magnitudes of association with CDI. Conclusions We found that both PPIs and vonoprazan were associated with CDI, and the magnitude of the association was comparable. Because vonoprazan is widely available in Asian countries, further studies on the association of its usage with CDI are warranted.

Vonoprazan-associated Clostridioides difficile infection: an analysis of the Japanese Adverse Drug Event Report and the FDA Adverse Event Reporting System

“…Although previous studies found that vonoprazan and PPIs use was positively associated with CDI, the association between vonoprazan and CDI is not beyond that of PPIs use. 36 , 37 However, previous findings have contradicted the effects of vonoprazan on the gut microbiome. 34 In this study, CDI signals were detected for both vonoprazan and PPIs, and the results of the ROR for the suspected drug calculated from the two databases showed that the ROR for vonoprazan was significantly greater than that of PPIs.…”

Impact of Functional Status on Development of <i>Clostridioides difficile</i> Infection and Increase in Inhospital Mortality among Antibiotic Users

“…This was a secondary analysis of a retrospective hospital-based cohort study in Japan. Details of the original study have been published elsewhere [5]. Briefly, we extracted data of all adult patients who were hospitalized to Akita City Hospital for ≥7 days between January 2016 and December 2020.…”

“…Nonsurvivors showed significantly higher rate of severe CDI (54.2% vs. 25.0%, p = 0.012) than survivors. Notably, non-survivors had significantly higher proportion of patients with high risk in the BC category and marginally higher CCI than survivors (83.3% vs. 48.7%, p = 0.004; 4 [2][3][4][5] vs. 2 [1][2][3][4], p = 0.054), while there were no significant differences in the remaining factors (Table 3).…”

“…In contrast, a variety of factors, including advanced age, comorbidities, prior hospital admission, antibiotic use, and gastric acid suppressant use, have been identified as potential risk factors for developing CDI [1‒4]. Indeed, our recent large-scale cohort study, including all hospitalized adult patients, demonstrated that advanced age and comorbid conditions were significantly associated with developing CDI [5].…”