Increasing Evidence of the Nephrotoxicity of Piperacillin/Tazobactam and Vancomycin Combination Therapy—What Is the Clinician to Do?

Early administration of appropriate empiric antibiotics is essential for achieving the best possible outcomes in sepsis. Yet the choice of antibiotic therapy has become more challenging due to recent reports of nephrotoxicity with the combination of vancomycin and piperacillin/tazobactam, the "workhorse" regimen at many institutions. In this article we assess the evidence for nephrotoxicity and its possible mechanisms, provide recommendations for risk mitigation, address the advantages and disadvantages of alternative antibiotic choices, and suggest areas for future research.