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More Acute Kidney Injury With Vancomycin Plus… Pip/Tazo Or Ceftolozane/Tazo?

September 15, 2022

Written by Seth Walsh-Blackmore

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Patients receiving vancomycin + piperacillin/tazobactam (VAN-TZP) had greater adjusted odds of acute kidney injury (AKI) than those receiving vancomycin + ceftolozane/tazobactam (VAN-C/T).

Why does this matter?
VAN-TZP is a common broad-spectrum empiric antibiotic regimen. Both agents are nephrotoxic and worse in combination . A new regimen with similar coverage and less nephrotoxicity would be an important addition to the empiric arsenal.

Maybe it wasn’t the contrast…
This was a multi-center retrospective study of adults receiving VAN-TZP or VAN-C/T for at least 48 hours. It included 90 VAN-C/T and 284 VAN-TZP patients, exceeding the power analysis goal. The primary outcome was a composite of AKI determined by meeting RIFLE, AKIN, or VIN criteria.

The primary outcome occurred in 25% of VAN-TZP group vs. 12.2% of the VAN-C/T group (p=0.011). After adjustment for confounding variables, VAN-TZP patients had an aOR of 3.31 (95% CI 1.56-6.99) for the primary outcome. Odds remained higher with VAN-TZP in subgroups excluding exposure to nephrotoxic medications (aOR 2.59 (1.05-6.41)) or adjusted for vancomycin trough levels (aOR 4.12(1.27-14.49)).

Several issues limit the importance of these data. Urine output, a component of the RIFLE criteria, was not recorded. Retrospective data make it difficult to confirm a baseline creatinine. Exposure to nephrotoxins is broadly categorized and represents a possible confounder despite adjustment. Fluid resuscitation was not reported. The primary outcome was a comparison of renal lab values, not patient-centered morbidity. There are already less nephrotoxic alternatives to VAN-TZP, which were not compared.

This study provides design-limited evidence that VAN-TZP is associated with more AKI criteria than VAN-C/T. It is hypothesis-generating but did not compare efficacy in treatment or patient-centered outcomes to guide a change in clinical practice.

Nephrotoxicity of Vancomycin in Combination with Beta-lactam Agents: Ceftolozane-tazobactam vs. Piperacillin-tazobactam. Clin Infect Dis. 2022 Aug 19;ciac670. doi: 10.1093/cid/ciac670. Online ahead of print.

What are your thoughts?