212 - Acute Kidney Injury with Piperacillin-tazobactam versus Cefepime in Combination with Vancomycin

Background: Drug-induced nephrotoxicity in the form of acute kidney injury (AKI) is a potential adverse effect of vancomycin, which is commonly prescribed empirically with an antipseudomonal agent.  It is unclear if combinations with certain antipseudomonal agents (e.g., piperacillin-tazobactam) are associated with more AKI relative to others.

Methods: This retrospective cohort study conducted at two Veterans Affairs (VA) Medical Centers with differing preferred empiric vancomycin-antipseudomonal regimens aimed to assess the incidence of AKI in patients receiving vancomycin and piperacillin-tazobactam (VPT) at VA Greater Los Angeles Healthcare System (HCS) versus vancomycin and cefepime (VC) at VA Long Beach HCS.  Patients who received VPT or VC for at least 48 hours in 2016-2018 were included.  AKI definitions were derived from 2012 Kidney Disease Improving Global Outcomes guidelines.  Secondary assessments included hospital length of stay, 90-day mortality, and incidence of Clostridioides difficile infection (CDI) within 90 days.  Patients who developed AKI were further assessed for time-to-onset of AKI, development of chronic kidney disease (CKD) within 90 days, and hemodialysis (HD) dependence within 1 year.  Statistical analysis was performed using Fisher’s exact and Mann-Whitney U tests where appropriate.  Propensity score matching using logistic regression with nearest-neighbor matching was performed to control for potential confounding baseline characteristics.

Results: 21/120 patients receiving VPT developed AKI vs. 4/120 receiving VC (17.5% vs. 3.3%, p=0.0005).  After propensity score matching, AKI incidence remained significantly higher for VPT patients (15.2% vs. 4.0%, p=0.01).  Median length of stay was significantly longer for VPT patients (10 days vs. 8 days, p=0.03).  There was no significant difference in time-to-onset of AKI, 90-day mortality, or CDI.  No significant difference was found in the development of CKD within 90 days nor the requirement of HD within 1 year.

Conclusion: VPT combination therapy was associated with increased incidence of AKI compared to VC, though 90-day mortality and other outcomes were similar.  Advising prescribers about potentially increased risk of AKI with VPT is a viable stewardship intervention.