Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

Abstract

Objectives: Proton pump inhibitor (PPI) therapy is a potentially modifiable risk factor for recurrent Clostridioides difficile infection (CDI). Citing an absence of clinical trials, many guidelines do not provide recommendations for addressing PPI management. Our aim was to perform an updated systematic review and meta-analysis evaluating the association between PPI use and recurrent CDI addressing prior methodological limitations. Methods: Data sources were MEDLINE and EMBASE. Eligible studies were cohort and caseecontrol studies; there were no restrictions on study setting or duration of follow-up. Participants were adults with prior CDI who did or did not receive PPI therapy and were assessed for recurrent CDI. Summary (unadjusted) odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Prespecified subgroup analyses were performed to explore heterogeneity including study design, study quality, duration of follow-up, adjustment for confounders, and outcome definition. Results: Sixteen studies were included in the meta-analysis, comprising 57 477 patients with CDI, of whom 6870 (12%) received PPIs. The rate of recurrent CDI was 24% in patients treated with PPIs versus 18% in those who were not. A meta-analysis that pooled unadjusted odds ratios demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.69, 95%CI 1.46e1.96) versus those who did not. There was moderate heterogeneity between studies (I 2 56%); however, a sensitivity analysis restricted to studies with 56 days of follow-up substantially reduced the heterogeneity (OR 1.59, 95%CI 1.36e1.85; I 2 12%). An analysis restricted to multivariate studies that combined adjusted ORs also demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.49, 95%CI 1.12e2.00). No publication bias was identified. Conclusions: We found significantly higher odds of recurrent CDI among users of PPIs that persisted across multiple sensitivity analyses. These results support stronger recommendations for PPI stewardship at CDI diagnosis.

Factors associated to potentially inappropriate prescribing in older patients according to STOPP/START criteria: MoPIM multicentre cohort study

“…With respect to PPIs, which are widely prescribed in Spain [34], they were classified as PIMs in 167 patients. PPIs may be related to adverse outcomes, such as fractures [35], hypomagnesaemia [36][37][38][39], recurrent C. difficile infection [40,41], dementia [42,43], communityacquired pneumonia [44], or severe COVID-19 infection [45][46][47]. Remarkably, in 160 (95.8%) patients, PPI prescription was assigned to implicit STOPP criterion A1.…”

“…The Updated Charlson Comorbidity Index [22] was calculated, adjusted by age and categorized by tertiles (2-6, 7-8 and 9-14). Barthel Index was categorized as independency (100 points), minimal dependency (60-95), moderate dependency (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55), severe dependency (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and complete dependency (<20) [23]. Some chronic conditions were grouped according to clinical criteria, as in Baré et.al.…”

Oral Vancomycin Prophylaxis for Primary and Secondary Prevention of Clostridioides difficile Infection in Patients Treated with Systemic Antibiotic Therapy: A Systematic Review, Meta-Analysis and Trial Sequential Analysis

“…For instance, the data on the concurrent use of gastric acid suppressant par excellence such as pump proton inhibitors (PPIs) were too sparse to assess the potential interaction of OVP with PPIs on CDI occurrence. At any rate, considering the well-known role of PPIs as risk factor for CDI [ 6 ], a so-called stewardship of acid-suppressing medication is warranted through systematic de-prescribing [ 68 ] Another limitation concerns the safety profile of OVP, because the rate of VRE infections is not the best measure to assess its potential negative impact on microbiota. Instead, the rate of VRE colonization should be evaluated.…”

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

“…However, it was noted that the most recent (and largest) RCT did not demonstrate any effect of pantoprazole versus placebo on 90-day mortality and a composite outcome of clinically important events [494]. A recent meta-analysis published since the finalisation of the literature searches has suggested that there is a higher risk of recurrent Clostridioides difficile infections with proton pump inhibitors [495].…”