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Canadian Journal of Gastroenterology and Hepatology
Volume 2016, Article ID 7431838, 9 pages
Review Article

Association between NSAIDs and Clostridium difficile-Associated Diarrhea: A Systematic Review and Meta-Analysis

1Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
2Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY 13326, USA
3Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand

Received 10 March 2015; Accepted 12 May 2015

Copyright © 2016 Nitipong Permpalung et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objective. Clostridium difficile infection is a leading cause of nosocomial diarrhea in developed countries. Studies evaluating the associations of increased risk of community-acquired CDAD and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. We conducted a systematic review and meta-analysis to compare the odds of NSAID exposure in patients with CDAD versus patients without CDAD in both community-based and healthcare-associated settings. Methods. Relevant observational studies indexed in PubMed/MEDLINE and EMBASE up to February 2015 were analyzed and data were extracted from nine studies. Of these, eight studies were included in the meta-analysis. Results. A search of the databases resulted in 987 articles. The nine studies from which data were extracted involved over 39,000 subjects. The pooled odds ratio for history of NSAID use in participants with CDAD compared with controls was 1.41 (95% CI 1.06–1.87; ), indicating a significant increased odds of CDAD among patients exposed to NSAIDs. Conclusions. To the best of our knowledge, this is the first study of its nature to demonstrate the association between the use of NSAIDs and increased risk of CDAD. Further studies to evaluate if any specific types of NSAIDs can increase the risk of CDAD are warranted.