Nut Cracked? Does the ACORN Trial End the Debate Surrounding Vancomycin and Piperacillin-Tazobactam Combination Therapy and Increased Risk for Acute Kidney Injury?

Observational data published over the past decade have suggested that concomitant receipt of piperacillin-tazobactam with vancomycin significantly increases the risk for vancomycin-associated acute kidney injury. Importantly, however, there is significant controversy surrounding this association, and debate continues about the veracity of the risk. Given this ongoing debate, the recently published "Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial" is of tremendous interest to the infectious diseases community. In ACORN, the authors conclude that there was no association between receipt of cefepime or piperacillin-tazobactam and the primary outcome of acute kidney injury or death by day 14, despite the fact that >75% of the population received concomitant vancomycin. In this perspective, we provide a brief history on the controversy, provide a critical analysis of the ACORN findings, and ultimately discuss how these data help inform the ongoing debate.