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

Abstract

Introduction: 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.

Figure 1

Patient evaluation and stratification.

Figure 2

The relationship between proton pump inhibitors, antibiotics and Clostridium difficile. For pair-wise comparisons, ^* P = 0.013; ^† P = 0.777; ^‡ P = 0.585.