Piperacillin/Tazobactam and Antibiotic-Associated Acute Kidney Injury in Critically Ill Children

Abstract

Antibiotic-associated AKI is prevalent and contributes to substantial morbidity and mortality in critically ill pediatric patients. Little is known about how empiric use of broad-spectrum antibiotics affects development of AKI. The authors show that treatment of critically ill children with piperacillin/tazobactam within the first 48 hours of intensive care unit admission is associated with subsequent development of AKI. They demonstrate a weaker, nonsignificant association between AKI and piperacillin/tazobactam used in combination with vancomycin in this population. This second finding adds to uncertainty about the nephrotoxicity of piperacillin/tazobactam in this highly susceptible population. Cefepime, a potential alternative antibiotic, which was not associated with AKI in the study, may be a suitable alternative for some indications. There continues to be uncertainty about whether piperacillin/tazobactam (TZP) increases the risk of AKI in critically ill pediatric patients. We sought to compare rates of AKI among critically ill children treated with TZP or cefepime, an alternative frequently used in intensive care units, with and without vancomycin. We conducted a retrospective cohort study assessing the risk of AKI in pediatric intensive care unit patients after exposure to vancomycin, TZP, and cefepime, alone or in combination, within 48 hours of admission. The primary outcome was development of stage 2 or 3 AKI or an increase in AKI stage from 2 to 3 within the 6 days after the 48-hour exposure window. Secondary outcomes included lengths of stay, need for RRT, and mortality. Of 5686 patients included, 494 (8.7%) developed stage 2 or 3 AKI. The adjusted odds of developing AKI after medication exposure were 1.56 for TZP (95% confidence interval [95% CI], 1.23 to 1.99), 1.13 for cefepime (95% CI, 0.79 to 1.64), and 0.86 for vancomycin (95% CI, 0.69 to 1.07). The adjusted odds of developing AKI for vancomycin plus TZP versus vancomycin plus cefepime was 1.38 (95% CI, 0.85 to 2.24). Observational data in critically ill children show that TZP use is associated with increased odds of AKI. A weaker, nonsignificant association between vancomycin plus TZP and AKI compared with vancomycin plus cefepime, creates some uncertainty about the nature of the association between TZP and AKI. However, cefepime is an alternative not associated with AKI.