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

D'Silva et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.01.008, PROSPERO CRD42020203084
May 2021  
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PPIs for COVID-19
1st treatment shown to increase risk in September 2020
 
*, now with p = 0.00000031 from 37 studies.
* From meta analysis with ≥3 studies.
4,800+ studies for 102 treatments. c19early.org
Meta-analysis of 16 studies with 57,477 patients showing significantly higher risk of recurrent Clostridioides difficile infection (CDI) in patients prescribed proton pump inhibitors (PPIs) compared to those not prescribed PPIs. The association between PPI use and higher risk of CDI recurrence persisted across multiple subgroup and sensitivity analyses.
D'Silva et al., 31 May 2021, peer-reviewed, 7 authors, trial PROSPERO CRD42020203084. Contact: emily.mcdonald@mcgill.ca.
This PaperPPIsAll
Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis
Kristin M D'silva, Raaj Mehta, Michael Mitchell, Todd C Lee, Vibha Singhal, Marnie Goodwin Wilson, Emily G Mcdonald
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.01.008
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.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.cmi.2021.01.008 .
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