The Risk of Acute Kidney Injury in Critically Ill Patients Receiving Concomitant Vancomycin With Piperacillin-Tazobactam or Cefepime

J Intensive Care Med. 2020 Dec;35(12):1434-1438. doi: 10.1177/0885066619828290. Epub 2019 Feb 10.


Purpose: The objective of this study was to compare the incidence of acute kidney injury (AKI) among critically ill patients receiving combination therapy with vancomycin plus piperacillin-tazobactam (VPT) against patients receiving vancomycin plus cefepime (VC).

Methods: A retrospective cohort study of adult patients admitted to an intensive care unit between September 2012 and December 2016 was conducted. Patients were included if they received combination therapy with VPT or VC for ≥48 hours. Patients were excluded if creatinine clearance was <60 mL/min or received renal replacement therapy prior to the initiation of therapy. The primary end point was AKI, as defined by the Acute Kidney Injury Network classification, during or within 48 hours of completion of therapy. The incidence of AKI was compared between groups and multivariate analysis was performed to control for relevant confounders.

Results: A total of 394 patients received either VPT (n = 258) or VC (n = 136). There were no differences in baseline serum creatinine (0.8 [0.3]mg/dL vs 0.7 [0.3] mg/dL, P = 0.207), use of vasopressors (44% vs 38%, P = 0.255), mechanical ventilation (45% vs 40%, P = 0.350), or initial vancomycin trough (11.2 [5] mg/L vs 11 [4.8] mg/L, P = 0.668) between VPT and VC groups, respectively. The incidence of AKI was 28.7% for VPT patients versus 21.3% for VC patients (P = 0.114). Multivariate analysis revealed vancomycin trough >20 mg/L (odds ratio, OR [95% confidence interval, CI] = 2.69 [1.62-4.47]), baseline SCr (OR [95% CI] = 3.34 [1.43-7.80]), vasopressors (OR [95% CI] = 1.77 [1.04-3.04]), and duration of combination therapy (OR [95% CI] = 1.009 [1.003-1.015]) as independent risk factors for AKI.

Conclusion: The risk of AKI was similar between VPT and VC groups in critically ill patients. Risk factors for AKI were related to baseline renal function, duration of combination therapy, supratherapeutic vancomycin troughs, and severity of illness.

Keywords: intensive care unit; kidney injury; vancomycin; β-lactams.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Cefepime / administration & dosage
  • Cefepime / adverse effects
  • Critical Illness*
  • Drug Therapy, Combination
  • Humans
  • Piperacillin, Tazobactam Drug Combination / administration & dosage
  • Piperacillin, Tazobactam Drug Combination / adverse effects
  • Retrospective Studies
  • Vancomycin* / administration & dosage
  • Vancomycin* / adverse effects


  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Vancomycin
  • Cefepime