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

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.