Storage Duration of Red Blood Cell Transfusion and Clostridium difficile Infection: A Within Person Comparison

OBJECTIVE: Randomized controlled trials demonstrated that red blood cell (RBC) transfusion elevates the risk of infection, and trials are underway to evaluate whether RBC storage affects outcomes. We previously reported that transfusion predicts Clostridium difficile infection (CDI) and, therefore, planned an investigation to examine this further using a more robust design. DESIGN: Within-person case-crossover study. Hospitalizations in which CDI developed (n = 406) were compared to hospitalizations for the same individuals in which CDI did not occur (n = 949). Transfusion volume and storage duration were assessed prior to the onset of CDI. SETTING: University of Michigan Health System. PATIENTS: Participants were individuals with a diagnosis of CDI from July 2009 through June 2012. MEASUREMENTS AND MAIN RESULTS: During the hospitalizations when CDI occurred, 34.7% of the patients received allogeneic RBC transfusions (mean volume, 688 ml) compared to 19.0% of patients in hospitalizations without CDI (mean volume, 180 ml). The odds of healthcare-associated CDI increased by 76% (95% CI 1.39–2.23) for every liter of RBCs transfused and was elevated in both nonsurgical (OR = 1.90) and surgical (OR = 1.86) hospitalizations. In patients who received RBC transfusions, the odds of developing CDI increased by 6% for every additional day of RBC stored and by 53% for every week of additional storage (P = 0.002). CONCLUSIONS: Hospitalizations in which a patient received a greater volume of RBC transfusions were more likely to be associated with the development of CDI. RBC units stored for a longer duration were associated with the development of healthcare-associated CDI after adjustment for RBC volume.