title: Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy.
abstract: BACKGROUND
  The association between the use of proton pump inhibitors and the risk of Clostridium difficile-associated disease (CDAD) is controversial. In this study we re-examined a previously reported association between the use of proton pump inhibitors and the development of community-acquired CDAD, this time using an alternative case definition of the disease.
  
  
  METHODS
  We performed a case-control study of community-acquired CDAD using a United Kingdom clinical research database. Patients receiving oral vancomycin therapy were identified as having CDAD, the only indication for this drug. Each case subject was matched with up to 10 control subjects. Neither the cases nor the controls had been admitted to hospital in the year before the date of the vancomycin prescription (index date). Conditional logistic regression analysis was used to adjust for key covariates.
  
  
  RESULTS
  We identified 317 cases of community-acquired CDAD treated with oral vancomycin therapy and 3167 matched control subjects. Exposure to a proton pump inhibitor in the 90 days before the index date was associated with an increased risk of CDAD (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.3-5.2). Antibiotic exposure in the 90 days before the index date was also a significant risk factor for community-acquired CDAD (OR 8.2, 95% CI 6.1- 11.0), even though 45% of the case subjects had not received a prescription for an antibiotic during that period. Certain comorbidities, in particular renal failure, inflammatory bowel disease and malignant disease, as well as prior methicillin-resistant Staphylococcus aureus infection, were also associated with an increased risk.
  
  
  CONCLUSIONS
  Proton pump inhibitor use was associated with an increased risk of community-acquired CDAD, when cases were defined by receipt of prescription for oral vancomycin therapy. Prior antibiotic exposure was also a significant risk factor, but a significant proportion of the patients with community-acquired CDAD had no such exposure.
authors.affiliation: Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University Health Centre, and the Department of Epidemiology and Biostatistics, McGill University, Montréal, Que. sandra.dial@mcgill.ca
authors.forename: Sandra
authors.initials: S
authors.lastname: Dial
authors.forename: J A Chris
authors.initials: JA
authors.lastname: Delaney
authors.forename: Verena
authors.initials: V
authors.lastname: Schneider
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D016360:Clostridioides difficile; D017714:Community-Acquired Infections; D015897:Comorbidity; D016208:Databases, Factual; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D054328:Proton Pump Inhibitors; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D014640:Vancomycin