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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.

Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients