Vancomycin, Zosyn and nephrotoxicity: should we be worried?

I hope readers will understand my using the name Zosyn instead of the more clunky piperacillin/tazobactam. I think the term “gone viral” well describes this concern. That is, the notion of the “nephrotoxic toxic vanc/zosyn combo” is spreading like wildfire (on the wards, via email, etc) though not so much through “official” media. It wasn't even mentioned in the nephrology or ID talks at the recent Society of Hospital Medicine national meeting. It's been difficult to find good information. But Academic Life in Emergency Medicine recently posted a topic review. As usual they did a great job. Their bottom line:

While there is no definitive link between pip-tazo and risk of AKI, there have been 5 different groups, with internal medicine and ICU patients, showing a possible association. To me, this adds one more reason to at least think twice about reflexively ordering pip-tazo for every sick patient.

In other words the evidence favoring the nephrotoxic association is low level but more and more is coming in in bits and pieces, adding to the concerns.

What I get tentatively from the available data, and this is just a hunch:

Vancomycin as nephrotoxic all by itself is a difficult sell for me. Maybe in patients who experience very high trough levels, but I don't know.

Zosyn as monotherapy appears to have nephrotoxic potential.

Vancomycin seems to potentiate the nephrotoxicity of Zosyn.