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Cited by 64Clostridium difficile and Clostridium perfringens researchPharmaceutical Practices and Patient OutcomesPharmacovigilance and Adverse Drug Reactions

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

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D'Silva, Kristin M., Mehta, Raaj, Mitchell, Michael, Lee, Todd C., Singhal, Vibha, Wilson, Marnie Goodwin, McDonald, Emily G.·2021·Clinical Microbiology and Infection
DOI 10.1016/j.cmi.2021.01.008
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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 case–control 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 1.46–1.96) 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 1.36–1.85; 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 1.12–2.00). 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.

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Authors
D'Silva, K. M., Mehta, R., Mitchell, M., Lee, T. C., Singhal, V., Wilson, M. G., & McDonald, E. G.
Affiliations
  • Harvard University (US)
  • Western University (CA)
  • McGill University Health Centre (CA)
  • Massachusetts General Hospital (US)
  • University of British Columbia (CA)
Corresponding author
McDonald, Emily G.
ORCID
Venue
Clinical Microbiology and Infection
Publisher
Elsevier BV
Published
2021-05
Volume
27
Issue
5
Pages
697-703
ISSN
1198-743X (ISSN-L)
DOI
10.1016/j.cmi.2021.01.008
OpenAlex
W3120567015
Cited by
64
References
46
Citations by year
2026: 9 · 2025: 11 · 2024: 14 · 2023: 17 · 2022: 9 · 2021: 4
FWCI
1.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Microbiology and Infection (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Fonds de Recherche du Québec - Santé
  • National Institutes of Health (T32-AR-007258)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords
proton pump inhibitors, recurrent Clostridium difficile infection, risk factors, antibiotic-associated diarrhea

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