A Large-Scale Multi-Center Retrospective Study on Nephrotoxicity Associated with Empiric Broad Spectrum Antibiotics in Critically Ill Patients

Chest. 2023 Apr 9:S0012-3692(23)00491-9. doi: 10.1016/j.chest.2023.03.046. Online ahead of print.

ABSTRACT

BACKGROUND: There is conflicting evidence regarding acute kidney injury (AKI) associated with concomitant administration of vancomycin and piperacillin/tazobactam (VPT), particularly in intensive care unit (ICU) patients.

RESEARCH QUESTION: Is there a difference in association between commonly prescribed empiric antibiotics on ICU admission (VPT, vancomycin and cefepime [VC], and vancomycin and meropenem [VM]) and AKI?

STUDY DESIGN AND METHODS: This study is a retrospective cohort study using data from the eICU Research Institute (eRI), which contains records for ICU stays between 2010 to 2015 across 335 hospitals. Patients were enrolled if they received VPT, VC, or VM exclusively. Patients initially admitted to the emergency department were included. Patients with hospital stay duration<1h, on dialysis, or missing data were excluded. AKI was defined as KDIGO stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match control (VM or VC) and treatment patients (VPT), and odds ratios were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission.

RESULTS: 35,654 patients met inclusion criteria (VPT n=27,459; VC n=6,371; VM n=1,824). VPT had a higher risk of AKI and initiation of dialysis when compared to that of both VC (AKI: OR, 1.37; 95% CI, 1.25-1.49; dialysis: OR, 1.28; 95% CI, 1.14-1.45) and VM (AKI: OR, 1.27; 95%, 1.06-1.52; dialysis: OR, 1.56; 95% CI, 1.23-2.00). The odds of developing AKI was especially pronounced in patients without renal insufficiency receiving longer duration therapy of VPT compared to VM.

INTERPRETATION: VPT is associated with a higher risk of AKI than both VC and VM in ICU patients, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider VM or VC to reduce the risk of nephrotoxicity for ICU patients.

PMID:37040818 | DOI:10.1016/j.chest.2023.03.046