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The Impact of Clostridium difficile Infection on Mortality in Patients With Inflammatory Bowel Disease

A Systematic Review and Meta-Analysis

Tariq, Raseen, MBBS*,†; Law, Cindy C.Y., BSc; Khanna, Sahil, MBBS, MS*; Murthy, Sanjay, MD, MSc; McCurdy, Jeffrey D., MD, PhD

Journal of Clinical Gastroenterology: February 2019 - Volume 53 - Issue 2 - p 127–133
doi: 10.1097/MCG.0000000000000968
ALIMENTARY TRACT: Original Articles

Background and Aims: Clostridium difficile infection (CDI) has been associated with an increased mortality risk among patients with inflammatory bowel disease (IBD) in multiple observational studies. We performed a systematic review and meta-analysis to help clearly define the magnitude of risk in IBD patients with and without CDI, and to assess the risk in individual IBD subtypes.

Methods: A systematic search of multiple electronic databases was conducted for observational studies reporting the risk of mortality in IBD, stratified by the presence of CDI. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale.

Results: Ten observational studies were identified (8 from North America and 2 from Europe) and included 40,700 IBD patients with CDI and 1,320,764 IBD controls without CDI. Overall, IBD patients with CDI had a higher risk of mortality compared with IBD patients without CDI [odds ratios (OR), 4.39; 95% confidence interval (CI), 3.56-5.42; I 2=93%]. The results were stable in high-quality studies and in hospitalized patients. When patients were stratified by IBD type, CDI was associated with increased mortality in patients with ulcerative colitis (7 studies) (OR, 4.39; 95% CI, 3.44-5.61; I 2), but not in patients with Crohn’s disease (4 studies) (OR, 2.21; 95% CI, 0.84-5.77; I 2). Individual studies were limited by an inability to control for IBD disease activity and therapeutic interventions.

Conclusions: On the basis of 10 observational studies with at least moderate quality, CDI seems to increase mortality risk in IBD, particularly in ulcerative colitis. These findings are a cause for concern and suggest that CDI should be managed aggressively in patients with IBD.

*Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN

Department of Internal Medicine, Rochester General Hospital, Rochester, NY

Department of Medicine, The Ottawa Hospital IBD Centre, University of Ottawa, Ottawa, ON

R.T. and C.C.Y.L. contributed equally.

R.T. and C.C.Y.L.: study identification, data acquisition, drafting of the manuscript. S.K.: study concept design, drafting of the manuscript, critical review of the manuscript. S.M.: critical review of the manuscript. J.D.M.: study concept design, data analysis, drafting of the manuscript.

The authors declare that they have nothing to disclose.

Address correspondence to: Raseen Tariq, MBBS, Division of Gastroenterology, Mayo Clinic, Rochester, MN, 200 1st Street SW, Rochester, MN 55905 (e-mail:

Received July 31, 2017

Accepted October 23, 2017

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.