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Comorbidities, Exposure to Medications, and the Risk of Community-Acquired Clostridium difficile Infection: A Systematic Review and Meta-analysis

Published online by Cambridge University Press:  22 December 2014

Luis Furuya-Kanamori*
Research School of Population Health, Australian National University, Canberra, Australia
Jennifer C. Stone
School of Population Health, University of Queensland, Herston, Australia
Justin Clark
Drug ARM Australasia, Annerley, Australia
Samantha J. McKenzie
School of Population Health, University of Queensland, Herston, Australia
Laith Yakob
Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK
David L. Paterson
University of Queensland, UQ Centre for Clinical Research, Herston, Australia
Thomas V. Riley
Microbiology & Immunology, University of Western Australia, and Department of Microbiology PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia
Suhail A. R. Doi
School of Population Health, University of Queensland, Herston, Australia
Archie C. Clements
Research School of Population Health, Australian National University, Canberra, Australia
Address correspondence to Luis Furuya-Kanamori, MEpi, Research School of Population Health, Australian National University, Canberra, ACT 2601, Australia (



Clostridium difficile infection (CDI) has been extensively described in healthcare settings; however, risk factors associated with community-acquired (CA) CDI remain uncertain. This study aimed to synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI.


A systematic search was conducted in 5 electronic databases for epidemiologic studies that examined the association between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted.


Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80–10.04) and corticosteroid (1.81; 1.15–2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52–9.12), renal failure (2.64; 1.23–5.68), hematologic cancer (1.75; 1.02–5.68), and diabetes mellitus (1.15; 1.05–1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years.


Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening.

Infect Control Hosp Epidemiol 2014;00(0):1–10

Original Articles
© 2014 by The Society for Healthcare Epidemiology of America. All rights reserved 

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