Influence of antibiotics and case exposure on hospital-acquired Clostridium difficile infection independent of illness severity

Abstract

Previous studies of the association between antibiotic exposure and risk of hospital-acquired Clostridium difficile-associated infection (CDI) have not fully accounted for patient severity of illness, and competing risks. To determine the potential effects of interventions on hospital-acquired CDI risk. All adults admitted to a teaching hospital between 2004 and 2014 for more than two days were included. Exposures to all antibiotics and cases of CDI were determined. Patients were followed until discharge from hospital, death, or acquisition of hospital-acquired CDI (defined as positive toxin assay in unformed stool >2 days following admission). Multivariable proportional hazards competing-risks modelling with time-dependent covariates was used, accounting for patient severity of illness using the Escobar model. In all, 208,104 patients were studied. Hospital-acquired CDI risk was 0.46 events per 1000 patient-days, decreasing significantly during the study period. Compared to the 5th percentile hospital death risk (0.02%), patients with a 50% risk of death in hospital hadan adjusted hazard ratio (aHR) of hospital-acquired CDI of 5.5. Exposure to some antibiotics significantly increased hospital-acquired CDI risk, being highest for carbapenems (aHR: 1.47 after one week of continuous exposure) and intravenous vancomycin (aHR: 1.53). On the ward, sharing a room with other patients newly diagnosed with CDI significantly increased the risk of subsequent disease (aHR: 1.16 on CDI diagnosis day). The primary determinant of hospital-acquired CDI was patient severity of illness. Exposure to both antibiotics and other patients with CDI significantly increased the subsequent risk of hospital-acquired CDI but this risk was small relative to patient severity of illness.