Identification of population at risk for future Clostridium difficile infection following hospital discharge to be targeted for vaccine trials

Abstract

Background: Efforts to develop a Clostridium difficile vaccine are underway; identification of patients at risk for C. difficile infection (CDI) is critical to inform vaccine trials. We identified groups at high risk of CDI ≥ 28 days after hospital discharge. Methods: Hospital discharge data and pharmacy data from two large academic centers, in New York and Connecticut, were linked to active population-based CDI surveillance data from the Emerging Infections Program (EIP). Adult residents of the EIP surveillance area were included if they had an inpatient stay at a study hospital without prior history of CDI. The primary outcome was CDI by either toxin or molecular assay ≥28 days after an index hospitalization. Important predictors of CDI ≥ 28 days post discharge were initially identified through a Cox proportional hazards model (stepwise backward selection) using a derivation cohort; final model parameters were used to develop a risk score evaluated in the validation cohort. Results: Of the 35,186 index hospitalizations, 288 (0.82%) had CDI ≥ 28 days post discharge. After parameter selection, age, number of hospitalizations in the prior 90 days, admission diagnosis, and the use of 3rd/4th generation cephalosporin, clindamycin or fluoroquinolone antibiotic classes remained in the model. Using the validation cohort, the risk score was predictive (p < 0.001) with a c-score of 0.75. Based on the distribution of scores in the derivation cohort, we divided the patients into low and high risk groups. In the high risk group, 1.6% experienced CDI ≥ 28 days post discharge compared to 0.3% among our low risk group. Conclusions: Our study identified specific parameters for a risk score that can be applied at discharge to identify a patient population whose risk of CDI ≥ 28 days following an acute care hospitalization was 5 times greater than other patients.