Vancomycin and Piperacillin-Tazobactam or Cefepime and Sepsis-Associated AKI Trajectory

INTRODUCTION: The combination of vancomycin and piperacillin-tazobactam (V/PT) is associated with increases in serum creatinine compared to other antibiotic combinations. However, the available literature is limited to the study of incident acute kidney injury (AKI). The combination has not been evaluated in patients with AKI already present at time of initiation, and the degree to which the trajectory of AKI is influenced by this combination is unknown.

METHODS : This was a single center, retrospective cohort study of adult patients admitted to a medical intensive care unit (ICU) with sepsis and AKI present on admission prescribed a combination of V/PT or vancomycin and cefepime (V/C) within the first 72 hours of ICU admission. The primary outcome was maximum serum creatinine observed within days 2-7 of hospital admission. Secondary outcomes included AKI progression, need for kidney replacement therapy (KRT), major adverse kidney events (MAKE), ICU mortality, and ICU and hospital length of stay.

RESULTS: Of the 4,810 patients screened, 480 patients with sepsis and AKI met inclusion criteria. Two-hundred and eighty-eight (60%) received V/PT, and 192 (40%) received V/C. Patients were predominantly male (55.4%), Caucasian (89.8%), and had a comorbidity profile typically observed in medically critically ill patients. The groups were well-matched at baseline, including severity of illness, stage of AKI, exposure to other nephrotoxins, and durations of antimicrobial therapy. There were no differences in AKI trajectory over the course of the first week between the V/PT and V/C groups as assessed by maximum serum creatinine (2.1 [1.4-3.5] vs 2.1 [1.4-3.0] md/dL; p=0.46) and AKI progression (24% vs 23.4%; p=0.89). No differences were observed in other kidney-related outcomes, including the need for KRT or MAKE at hospital discharge. ICU mortality, ICU length of stay, and hospital length of stay also did not differ between the two groups.

CONCLUSIONS: The combination of V/PT compared to V/C was not associated with higher serum creatinine values or AKI progression during the week following ICU admission in patients with sepsis and AKI. This suggests the use of V/PT may be safe in patients with pre-existing AKI, and the combination need not be avoided based on nephrotoxicity concerns alone.