Does Piperacillin-Tazobactam Increase the Risk of Nephrotoxicity when Used with Vancomycin: A Meta-Analysis of Observational Trials

Curr Drug Saf. 2017;12(1):62-66. doi: 10.2174/1574886311666161024164859.


Background: Observational studies have suggested an increased risk of nephrotoxicity when piperacillin-tazobactam is added to vancomycin, although the data are confliciting.

Objective: To perform a meta-analysis of identified studies to assess if adding piperacillin-tazobactam to vancomycin increases the incidence of nephrotoxicity.

Method: A systematic review of PubMed, EMBASE, Cochrane Central, and Google Scholar was conducted to identify studies. Studies selected for meta-analysis were full length reports, retrospective or prospective, and designed specifically to assess if the combining piperacillin-tazobactam with vancomycin increases nephrotoxicity.

Results: Six observational trials involving 963 patients were identified and analyzed. Five trials were retrospective and one was prospective. Vancomycin/piperacillin-tazobactam was compared to vancomycin alone in 2 trials, to vancomycin/cefepime in 3 trials, and vancomycin/cefepime or meropenem in one. Meta-analysis showed a statistical increase in the incidence of nephrotoxicity when piperacillin-tazobactam/vancomycin is compared to the control group (2.26 95% CI 1.41-3.63, p= 0.0007). No differences were noted between groups in patients requiring renal replacement.

Conclusion: Adding piperacillin-tazobactam to vancomycin increases the risk of nephrotoxicity when compared to vancomycin alone or vancomycin with either cefepime or meropenem.

Keywords: Cefepime; combination; meropenem; meta-analysis; nephrotoxicity; piperacillin-tazobactam; vancomycin.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Drug Therapy, Combination
  • Humans
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / diagnosis
  • Kidney Diseases / epidemiology
  • Observational Studies as Topic / methods*
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / adverse effects
  • Penicillanic Acid / analogs & derivatives*
  • Piperacillin / administration & dosage
  • Piperacillin / adverse effects
  • Piperacillin, Tazobactam Drug Combination
  • Prospective Studies
  • Retrospective Studies
  • Vancomycin / administration & dosage
  • Vancomycin / adverse effects*


  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Vancomycin
  • Penicillanic Acid
  • Piperacillin