Kristin M D'Silva1, Raaj Mehta2, Michael Mitchell3, Todd C Lee4, Vibha Singhal5, Marnie Goodwin Wilson6, Emily G McDonald7. 1. Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA. 2. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA. 3. Division of Respirology, Department of Medicine, Western University, London, Ontario, Canada. 4. Clinical Practice Assessment Unit, McGill University Health Centre, Montreal, Canada; Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Canada. 5. Division of Pediatric Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. 6. Department of Medicine, University of British Columbia, Vancouver, Canada. 7. Clinical Practice Assessment Unit, McGill University Health Centre, Montreal, Canada; Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal, Canada. Electronic address: emily.mcdonald@mcgill.ca.
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 (I2 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; I2 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.
OBJECTIVES: Proton pump inhibitor (PPI) therapy is a potentially modifiable risk factor for recurrent Clostridioides difficileinfection (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 (I2 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; I2 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.
Authors: Laura Evans; Andrew Rhodes; Waleed Alhazzani; Massimo Antonelli; Craig M Coopersmith; Craig French; Flávia R Machado; Lauralyn Mcintyre; Marlies Ostermann; Hallie C Prescott; Christa Schorr; Steven Simpson; W Joost Wiersinga; Fayez Alshamsi; Derek C Angus; Yaseen Arabi; Luciano Azevedo; Richard Beale; Gregory Beilman; Emilie Belley-Cote; Lisa Burry; Maurizio Cecconi; John Centofanti; Angel Coz Yataco; Jan De Waele; R Phillip Dellinger; Kent Doi; Bin Du; Elisa Estenssoro; Ricard Ferrer; Charles Gomersall; Carol Hodgson; Morten Hylander Møller; Theodore Iwashyna; Shevin Jacob; Ruth Kleinpell; Michael Klompas; Younsuck Koh; Anand Kumar; Arthur Kwizera; Suzana Lobo; Henry Masur; Steven McGloughlin; Sangeeta Mehta; Yatin Mehta; Mervyn Mer; Mark Nunnally; Simon Oczkowski; Tiffany Osborn; Elizabeth Papathanassoglou; Anders Perner; Michael Puskarich; Jason Roberts; William Schweickert; Maureen Seckel; Jonathan Sevransky; Charles L Sprung; Tobias Welte; Janice Zimmerman; Mitchell Levy Journal: Intensive Care Med Date: 2021-10-02 Impact factor: 17.440