title: Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection: population-based case-control study using administrative data.
abstract: Community-associated Clostridium difficile infection (CA-CDI; defined as cases without prior hospitalization in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescribing of antimicrobials in primary care and CA-CDI.
  
  
  
  Three national patient-level datasets, covering CDI cases, community prescriptions and hospitalizations, were linked by the NHS Scotland unique patient identifier, the Community Health Index (CHI). All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression.
  
  
  
  The 1446 unique cases of CA-CDI were linked with 7964 age-, sex- and location-matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with more than 28 DDDs to any antimicrobial (19.9% of cases) had an OR of 4.4 (95% CI 3.4-5.6) compared with those unexposed. Individuals exposed to 29+ DDDs of high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR of 17.9 (95% CI 7.6-42.2). Elevated CA-CDI risk following high-risk antimicrobial exposure was greatest in the first month (OR = 12.5, 95% CI 8.9-17.4), but was still present 4-6 months later (OR = 2.6, 95% CI 1.7-3.9). Cases exposed to 29+ DDDs had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long-term prophylactic use.
  
  
  
  This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials, with an impact of exposure to high-risk antimicrobials remaining 4-6 months later.
authors.affiliation: Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK.|Information Services Division, NHS National Services Scotland, Edinburgh, UK.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Kavanagh
authors.affiliation: Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK.
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Pan
authors.affiliation: Population Health Sciences, School of Medicine, University of Dundee, Dundee, UK.
authors.forename: Charis
authors.initials: C
authors.lastname: Marwick
authors.affiliation: Population Health Sciences, School of Medicine, University of Dundee, Dundee, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Davey
authors.affiliation: Health Protection Scotland, NHS National Services Scotland, Glasgow, UK.
authors.forename: Camilla
authors.initials: C
authors.lastname: Wiuff
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Bryson
authors.affiliation: Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK.|Health Protection Scotland, NHS National Services Scotland, Glasgow, UK.|International Prevention Research Institute, Lyon, France.
authors.forename: Chris
authors.initials: C
authors.lastname: Robertson
authors.affiliation: Information Services Division, NHS National Services Scotland, Edinburgh, UK.|Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Bennie
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D016360:Clostridioides difficile / Q000302:isolation & purification; D003015:Clostridium Infections / Q000453:epidemiology* / Q000635:transmission; D017714:Community-Acquired Infections / Q000453:epidemiology*; D011307:Drug Prescriptions; D005260:Female; D006760:Hospitalization; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D012606:Scotland / Q000453:epidemiology; D065093:beta-Lactamase Inhibitors / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D019980:Amoxicillin-Potassium Clavulanate Combination