title: Comorbidities, Exposure to Medications, and the Risk of Community-Acquired Clostridium difficile Infection: a systematic review and meta-analysis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: 1Research School of Population Health,Australian National University,Canberra,Australia.
authors: Luis
authors: L
authors: Furuya-Kanamori
authors: 2School of Population Health,University of Queensland,Herston,Australia.
authors: Jennifer C
authors: JC
authors: Stone
authors: 3Drug ARM Australasia,Annerley,Australia.
authors: Justin
authors: J
authors: Clark
authors: 2School of Population Health,University of Queensland,Herston,Australia.
authors: Samantha J
authors: SJ
authors: McKenzie
authors: 4Department of Disease Control,London School of Hygiene & Tropical Medicine,London,UK.
authors: Laith
authors: L
authors: Yakob
authors: 5University of Queensland,UQ Centre for Clinical Research,Herston,Australia.
authors: David L
authors: DL
authors: Paterson
authors: 6Microbiology & Immunology,University of Western Australia, andDepartment of Microbiology PathWest Laboratory Medicine,Queen Elizabeth II Medical Centre,Nedlands,Australia.
authors: Thomas V
authors: TV
authors: Riley
authors: 2School of Population Health,University of Queensland,Herston,Australia.
authors: Suhail A R
authors: SA
authors: Doi
authors: 1Research School of Population Health,Australian National University,Canberra,Australia.
authors: Archie C
authors: AC
authors: Clements
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016360:Clostridioides difficile; D017714:Community-Acquired Infections / Q000453:epidemiology; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology*; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D019337:Hematologic Neoplasms / Q000453:epidemiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000453:epidemiology*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors