UMEM Educational Pearls

Title: Empiric antibiotics for sepsis and associated AKI -- avoid vanc-and-zosyn right?

Keywords: sepsis, antibiotics, AKI, ACORN, zosyn, piperacillin-tazobactam, cefepime (PubMed Search)

Posted: 1/31/2024 by Kami Windsor, MD (Updated: 12/26/2024)
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Background: For better or worse, the combination of “vanc-and-zosyn” has long been a go-to empiric regimen for the treatment of septic shock. Piperacillin-tazobactam is known to cause decreased creatinine secretion into the urine leading to an increased serum creatinine without any actual physiologic harm to the kidney, but the results of previous studies have led researchers to posit an increase in actual AKI with the vanc and zosyn combo. This concern has led to some physicians choosing cefepime for anti-pseudomonal gram-negative coverage instead, despite its known potential for neurotoxicity and cefepime-associated encephalopathy.

The ACORN trial: The recently published ACORN trial compared cefepime to piperacillin-tazobactam in adult patients presenting to the ED or medical ICU with sepsis or suspected serious infection. The primary outcome was a composite of highest stage of AKI or death at 14 days.

Single-center, unblinded, pragmatic, randomized control trial
2500 patients, approx. 20% with chronic kidney disease
Approximately 77% received vancomycin as well
~20% antibiotic crossover in each group

Results:

No difference between groups in the primary outcome, or in major adverse kidney events, even in subgroup that also received vancomycin
No difference in hospital length of stay, vasopressor days, ventilator days
Slightly higher incidence of delirium or coma in the cefepime group

Bottom Line: Good antibiotic stewardship would probably decrease the frequency of vanc-and-zosyn administration, but concern for renal dysfunction alone shouldn’t guide the choice between cefepime or piperacillin-tazobactam, even in those with CKD, and even in those patients also receiving vancomycin.

References

Qian ET, Casey JD, Wright A, et al. Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial. JAMA. 2023 Oct 24;330(16):1557-1567. doi: 10.1001/jama.2023.20583.