Nephrotoxicity of piperacillin/tazobactam combined with vancomycin: should it be a concern?

Int J Antimicrob Agents. 2018 Aug;52(2):180-184. doi: 10.1016/j.ijantimicag.2018.03.024. Epub 2018 Apr 9.


The combination of piperacillin/tazobactam (TZP) and vancomycin (VAN) provides a wide spectrum of activity against many pathogens acquired in healthcare settings. However, there have been reports of increased potential for nephrotoxicity with this combination. The aim of this study was to evaluate the nephrotoxic effect of TZP+VAN and to compare it with that of TZP and VAN monotherapies as well as VAN + meropenem (MEM), another broad-spectrum combination. A total of 402 patients receiving any of the antimicrobial regimens for >48 h were evaluated retrospectively over a 2-year period (2012-2013). Patients admitted to the intensive care unit, those with a baseline serum creatinine >2.0 mg/dL, patients on haemodialysis or peritoneal dialysis, pregnant women and those in septic shock were excluded. The presence and severity of acute kidney injury (AKI) was assessed according to the AKIN criteria. The incidence of AKI was significantly higher in the TZP+VAN group (41.3%) compared with the TZP (16.0%), VAN (15.7%) and VAN+MEM (10.1%) groups (P < 0.001). In the multivariate analysis, the risk of AKI increased 3.5-fold in patients treated with TZP+VAN and 1.7-fold in those who were receiving a potentially nephrotoxic drug when the antibiotic regimen was started compared with patients treated with VAN alone. Combined use of TZP+VAN carries a much higher risk of AKI than either antibiotic monotherapy regimen. Therefore, this broad-spectrum combination should be used cautiously in patients with a high likelihood of developing kidney injury.

Keywords: Acute kidney injury; Meropenem; Nephrotoxicity; Piperacillin/tazobactam; Vancomycin.

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / pathology
  • Adult
  • Aged
  • Creatinine / blood
  • Drug Therapy, Combination / adverse effects*
  • Female
  • Humans
  • Kidney / drug effects*
  • Kidney / pathology
  • Logistic Models
  • Male
  • Meropenem
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Middle Aged
  • Penicillanic Acid / adverse effects
  • Penicillanic Acid / analogs & derivatives*
  • Piperacillin / adverse effects
  • Piperacillin, Tazobactam Drug Combination
  • Pseudomonas Infections / blood
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Retrospective Studies
  • Staphylococcal Infections / blood
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Thienamycins / adverse effects*
  • Vancomycin / adverse effects*


  • Thienamycins
  • Piperacillin, Tazobactam Drug Combination
  • Vancomycin
  • Penicillanic Acid
  • Creatinine
  • Meropenem
  • Piperacillin