Impact of piperacillin/tazobactam on nephrotoxicity in patients with Gram-negative bacteraemia

Int J Antimicrob Agents. 2019 Mar;53(3):343-346. doi: 10.1016/j.ijantimicag.2018.11.002. Epub 2018 Nov 8.

Abstract

Piperacillin/tazobactam (TZP) has been associated with nephrotoxicity in patients receiving vancomycin. Its impact on nephrotoxicity in patients with Gram-negative bacteraemia (GNB) is unclear. This study evaluated the impact of TZP on nephrotoxicity in patients with GNB. This retrospective cohort included patients aged ≥18 years receiving ≥48 h of therapy for bacteraemia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter or Stenotrophomonas maltophilia from 1/01/2008-8/31/2011. Patients with baseline serum creatinine (SCr) ≥3.5 mg/dL, polymicrobial infection or recurrent bacteraemia were excluded. Nephrotoxicity was defined as a ≥0.5 mg/dL increase in SCr or ≥50% increase from baseline for ≥2 consecutive days. Any variable demonstrating a 10% change in exposure effect was retained in the final model. All variables biologically reasonable causes of nephrotoxicity were also considered for inclusion. The median age of the cohort (n = 292) was 76 years; 38.0% had a cancer diagnosis and ICU residence was common (21.9%). There was no difference in nephrotoxicity incidence based on days of TZP received (0 days, 13.6%; 1-2 days, 14.7%; 3-4 days, 6.9%; ≥5 days, 16.7%; P = 0.71). In multivariable analysis, baseline SCr, total body weight and vasopressor use were independently associated with nephrotoxicity. Duration of TZP was not associated with nephrotoxicity in multivariable analysis (1-2 days, OR = 0.91, 95% CI 0.39-2.12; 3-4 days, OR = 0.48, 95% CI 0.10-2.46; ≥5 days, OR = 0.57, 95% CI 0.11-3.02). In this cohort of GNB patients, duration of TZP was not associated with nephrotoxicity.

Keywords: Acute kidney injury; Gram-negative bacteraemia; Nephrotoxicity; Piperacillin/tazobactam.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Bacteremia / drug therapy*
  • Female
  • Gram-Negative Bacterial Infections / drug therapy*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Piperacillin, Tazobactam Drug Combination / administration & dosage
  • Piperacillin, Tazobactam Drug Combination / adverse effects*
  • Retrospective Studies
  • beta-Lactamase Inhibitors / administration & dosage
  • beta-Lactamase Inhibitors / adverse effects*

Substances

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