Acute kidney injury with combination vancomycin and piperacillin-tazobactam therapy in the ICU: A retrospective cohort study

Int J Antimicrob Agents. 2020 Jul;56(1):106010. doi: 10.1016/j.ijantimicag.2020.106010. Epub 2020 May 12.

Abstract

Vancomycin and piperacillin-tazobactam are commonly used antibiotics. There is increasing evidence to indicate that these therapies in combination predispose patients to acute kidney injury (AKI). However, studies of intensive care unit (ICU) patients with these antibiotics have produced conflicting results. In this single-centre, retrospective cohort study, data was collected on ICU patients prescribed combination vancomycin and piperacillin-tazobactam (VPT) for at least 48 h, compared with patients prescribed vancomycin with either cefepime or meropenem (VMC) for the same time period. Primary outcome was incidence of AKI; secondary outcomes included a desirability of outcome ranking (DOOR) scale, and association between antibiotic duration and kidney injury. A total of 260 patients were included. AKI was observed in 27% of cases overall. Incidence of AKI was higher with VPT compared with VMC on bivariate (relative risk reduction [RRR] 1.9, 95% confidence interval [CI] 0.9-4.1, P = 0.08) and multivariate (RRR 2.2, 95% CI 1.0-4.9, P = 0.05) analyses. Longer duration of antibiotic therapy was associated with increased rates of AKI independent of which antibiotics were prescribed: RRR 4.9, 95% CI 2.1-11.1, P = <0.001 for 5-6 days compared with <5 days, and RRR 2.3, 95% CI 1.0-5.5, P = 0.05 for >7 days compared with <5 days. This study demonstrated an association between increased risk of nephrotoxicity and combination VPT therapy in ICU patients. The concept remains controversial, with recent suggestions that VPT does not truly cause nephrotoxicity. Given our findings and the weight of previous studies, there is a strong mandate to undertake prospective trials to resolve the issue.

Keywords: Acute kidney injury; Nephrotoxicity; Piperacillin-tazobactam; Vancomycin.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Aged
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Cefepime / adverse effects
  • Cefepime / therapeutic use
  • Critical Care / methods
  • Duration of Therapy
  • Female
  • Humans
  • Intensive Care Units / statistics & numerical data*
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Meropenem / adverse effects
  • Meropenem / therapeutic use
  • Middle Aged
  • Piperacillin, Tazobactam Drug Combination / adverse effects*
  • Piperacillin, Tazobactam Drug Combination / therapeutic use
  • Retrospective Studies
  • Vancomycin / adverse effects*
  • Vancomycin / therapeutic use
  • beta-Lactamase Inhibitors / adverse effects*
  • beta-Lactamase Inhibitors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • Piperacillin, Tazobactam Drug Combination
  • Vancomycin
  • Cefepime
  • Meropenem