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ACORN RCT – Piperacillin-Tazobactam or Cefepime?

November 3, 2023

Written by Samuel Rouleau

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In this randomized control trial (RCT) of patients receiving cefepime or piperacillin-tazobactam, there was no difference in risk of acute kidney injury (AKI) between the two groups. However, those who received cefepime were more likely to have neurologic side effects.

“Vanco-pime” or “Vanc-osyn”?
When a patient with suspected sepsis and risk factors for resistant gram-negative bacteria presents to the hospital, the first-line antibiotics are cefepime and piperacillin-tazobactam. A potential side effect of piperacillin-tazobactam is AKI, especially when used concomitantly with vancomycin. Cefepime crosses the blood brain barrier and has been reported to cause neurotoxicity. Until now, there has been no head-to-head trial comparing the adverse effects of cefepime and piperacillin-tazobactam.

This RCT included adult patients in the ED or medical ICU who were initiated on cefepime or piperacillin-tazobactam within 12 hours of hospital arrival. Cefepime was given as a 2g push every 8 hours, and piperacillin-tazobactam was given as a 3.375g bolus followed by a 4-hour infusion every 8 hours. The primary outcome was severity of AKI or death within 14 days. There were two secondary outcomes: 1) proportion of patients who had a major adverse kidney event at day 14; 2) number of days alive without delirium or coma.

2,634 patients were enrolled (1,124 in the cefepime group, 1,297 patients in the piperacillin-tazobactam group). Baseline characteristics were similar between the two groups. Concurrent vancomycin administration was similar between the two groups, approximately 75% in each. There was no difference in the primary outcome, highest stage of AKI or death at 14 days, between the groups: OR 0.95 (95%CI 0.80-1.13, p = 0.56). No difference was found for the secondary outcome of major adverse kidney event at day 14 between the two groups: absolute difference 1.4% (95%CI -1.0% to 3.8%). Those who received cefepime had fewer days alive without delirium or coma at 14 days: OR 0.79 (95%CI 0.65-0.95), absolute difference 3.4%. This difference persisted even when controlling for sedation at time of enrolment (OR, 0.78 [95% CI, 0.62-0.99]) and baseline delirium and coma (OR, 0.80 [95% CI, 0.63-1.01]).

How will this change my practice?
We sling around a lot of anti-pseudomonal agents in the ED. Here are my thoughts on the study:

  • This study has removed my hesitation to administer piperacillin-tazobactam and vancomycin in patients with underlying chronic kidney disease.
  • The neurotoxic side-effects of cefepime are confirmed by this study. Realistically, it will probably not guide my selection of cefepime in the ED, unless the patient is already delirious.
  • For critical patients with peritonitis or concern for intra-abdominal surgical pathology, I will pick piperacillin-tazobactam over cefepime, as piperacillin-tazobactam also offers anaerobic coverage.
  • Hospital-policy and antibiotic availability may leave you with no choice in the matter anyway!
  • Check your local antibiograms, as local rates of resistance may impact your choice.

Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial. JAMA. 2023 Oct 14:e2320583. doi: 10.1001/jama.2023.20583. Online ahead of print.

What are your thoughts?