title: Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients.
abstract: BACKGROUND
  Proton pump inhibitors (PPI) have been linked to Clostridium difficile infection (CDI) but there are few data specific to ICU patients. We evaluated duration of PPI exposure as a potential risk factor for hospital-acquired CDI in the ICU.
  
  
  METHODS
  This retrospective, case-control study was conducted using the Multiparameter Intelligent Monitoring in Intensive Care II database, a large publically available database of more than 35,000 ICU patients. Adult patients with CDI were identified using the ICD-9 code for Clostridium difficile listed as a secondary diagnosis. To be included, patients had to be present in an ICU for ≥ 48 hours prior to Clostridium difficile acquisition. These patients were then matched to patients without CDI using the ICD-9 primary diagnosis, age (+/-5 years) and SOFA score (+/-1). Successfully matched patients were reviewed for PPI exposure and other potential confounding variables for CDI. PPI exposure was characterized as short (<2 days) or long (≥ 2 days). Multivariate modeling was performed to identify independent risk factors for CDI.
  
  
  RESULTS
  There were 408 patients evaluated and 81% received a PPI. The percentage of patients who had a long exposure to PPIs was 83% in the CDI group compared to 73% with controls (P = 0.012). Upon inclusion of the following variables into a multivariate analysis (long PPI exposure, histamine-2-receptor antagonist administration, antibiotic administration, immunosuppression and study duration), long PPI exposure (odds ratio (OR) (95% confidence interval (CI) = 2.03 (1.23 to 3.36), P = 0.006) and antibiotic use (OR (95% CI) = 2.52 (1.23 to 5.18), P = 0.012) were identified as independent predictors of CDI.
  
  
  CONCLUSIONS
  Proton pump inhibitors are independent risk factors for the development of CDI in ICU patients. This risk is particularly exposed after two or more days of therapy.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy-Glendale, Midwestern University, 19555 N 59th Avenue, Glendale, AZ, 85308, USA. jbarle@midwestern.edu.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Barletta
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy-Glendale, Midwestern University, 19555 N 59th Avenue, Glendale, AZ, 85308, USA. dsclar@midwestern.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Sclar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D016638:Critical Illness / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000639:trends; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D054328:Proton Pump Inhibitors