Comparison of the Nephrotoxicity of Vancomycin in Combination With Cefepime, Meropenem, or Piperacillin/Tazobactam: A Prospective, Multicenter Study

Ann Pharmacother. 2018 Jul;52(7):639-644. doi: 10.1177/1060028018757497. Epub 2018 Feb 14.


Background: Patients often receive broad-spectrum antibiotics for nosocomial infections commonly with activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Previous retrospective and/or single-center studies have suggested that the combination of vancomycin and piperacillin/tazobactam might be associated with an increased risk of acute kidney injury.

Objectives: To compare the incidence of nephrotoxicity in patients receiving intravenous vancomycin in combination with cefepime, meropenem, or piperacillin/tazobactam.

Methods: This was a prospective, multicenter observational study of patients receiving vancomycin in combination with piperacillin/tazobactam versus cefepime or meropenem. Adult patients 18 years of age or older who were hospitalized and received 72 or more hours of intravenous vancomycin and 72 hours or more of cefepime, meropenem, or piperacillin/tazobactam were eligible. Patient and medication characteristics were examined for the 242 patients included.

Results: The incidence of acute kidney injury for patients treated with vancomycin and piperacillin/tazobactam was significantly higher than for those treated with vancomycin and cefepime or meropenem, 29.8% versus 8.8%, respectively, P < 0.001. Binary logistic regression demonstrated that patients receiving vancomycin and piperacillin/tazobactam were 6.7 times more likely to develop acute kidney injury compared with the other cohort.

Conclusions: The combination of vancomycin with piperacillin/tazobactam significantly increases the risk of acute kidney injury compared with other broad-spectrum antibiotic combinations. Clinicians should be vigilant when employing this regimen.

Keywords: antibiotics; beta-lactams; cephalosporins; nephrotoxicity; vancomycin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Bacterial Infections / drug therapy
  • Cefepime / adverse effects
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Meropenem / adverse effects
  • Middle Aged
  • Piperacillin, Tazobactam Drug Combination / adverse effects*
  • Retrospective Studies
  • Vancomycin / adverse effects*


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