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

Critical Care, Dec 2014

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.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://ccforum.com/content/pdf/s13054-014-0714-7.pdf

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

Jeffrey F Barletta 0 David A Sclar 0 0 Department of Pharmacy Practice, College of Pharmacy-Glendale, Midwestern University , 19555 N 59th Avenue, Glendale, AZ 85308 , USA 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. - Introduction Clostridium difficile infection (CDI) is the leading cause of hospital-associated infectious diarrhea with considerable impact on length of stay and costs [1]. The prevalence of CDI in mechanically ventilated, intensive care unit (ICU) patients is 6.6% with most cases (69%) being diagnosed during the ICU admission [2]. The high frequency of CDI in critically ill patients is particularly concerning given the multiple risk factors that are present and the increased risk for adverse outcomes in this population. Recently, proton pump inhibitors (PPIs) have been widely implicated as a significant risk factor for hospitalacquired CDI [3-9]. In one large database study of ICU patients, the odds ratio (OR) for CDI was significantly greater with PPI use compared to histamine-2-receptor antagonists (H2RA) (OR (95% confidence interval (CI) = 1.29 (1.04 to 1.64)). Infection-related risks with PPIs are believed to be greatest shortly after starting therapy [3,10-12]. One study evaluating the relationship between duration of PPI therapy and nosocomial CDI revealed a significant increase in risk after only two days of PPI use [3]. PPIs have become the most common modality for the provision of stress ulcer prophylaxis (SUP) in critically ill patients [13,14]. While PPI use for this indication is generally short-term, even an abbreviated exposure could lead to substantial increases in morbidity and overall hospital costs. The objective of this study was to further describe the relationship between PPI use and hospitalacquired CDI in critically ill patients and evaluate duration of inpatient PPI exposure as a risk factor for CDI. Methods This case-control study was conducted using the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database, version 2.6 [15,16]. This database is a large, publically available database that encompasses more than 35,000 patients admitted to the Beth Israel Deaconess Medical Center from 2001 to 2008. Beth Israel Deaconess Medical Center is a 620-bed tertiary academic medical center in Boston, MA, USA with 77 critical care beds [16]. The MIMIC II database provides a high-resolution record of time-stamped clinical variables, physiologic data, diagnoses and interventions that have been de-identified in a Health Insurance Portability and Accountability Act-compliant manner. The database was queried in August, 2013. Institutional Review Board approval was obtained (Midwestern University, AZ#754) prior to study initiation. The need for informed consent was waived. Adult patients with CDI were first identified using the International Classification of Diseases, Ninth Revision (ICD-9) code for Clostridium difficile (008.45) listed as a secondary diagnosis. To be included, patients had to be present in an ICU for at least 48 hours prior to its acquisition. These patients were then matched to patients without CDI in a 1-to-1 ratio using the ICD-9 primary diagnosis, Sequential Organ Failure Assessment (SOFA) score (+/1) and age (+/5 years). Patients were excluded if Clostridium difficile was listed as a primary admitting diagnosis, if a successful match could not be obtained or if the medication rec (...truncated)


This is a preview of a remote PDF: http://ccforum.com/content/pdf/s13054-014-0714-7.pdf

Jeffrey F Barletta, David A Sclar. Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients, Critical Care, 2014, pp. 714, 18, DOI: 10.1186/s13054-014-0714-7