Zosyn: Why I Don't Worry About Nephrotoxicity

This transcript has been edited for clarity.

Is piperacillin-tazobactam (Zosyn) nephrotoxic? It's a question that has come up repeatedly during my past 2 weeks on our infectious disease consultation service in the hospital, especially among house staff and advanced-level practitioners.

Here's the back story. Over a decade ago, the FDA placed warnings in the prescribing information for piperacillin-tazobactam that in critically ill patients, it can affect renal function, and they suggested using alternative agents. They also warned about combining piperacillin-tazobactam with vancomycin because of the risk for increased acute kidney injury. Some of this was based on a 1200-patient trial, indicating about a 70% increased risk for renal failure with piperacillin/tazobactam compared with other beta-lactam drugs.

So, what's happened in the ensuing decade, especially for more ill patients or those with some baseline renal abnormalities is that cefepime (a cephalosporin) became the favored drug when you need gram-negative coverage, and use of piperacillin/tazobactam declined.

However, I would say the warning has always been a bit controversial because before that study was performed, piperacillin, like any beta-lactam, can rarely cause acute interstitial nephritisbut it is rare and the drug generally wasn't considered nephrotoxic. But a whole bunch of me-too studies that were often observational or retrospective seemed to confirm this problem and helped to reinforce the point of view that piperacillin-tazobactam could be nephrotoxic