In this episode, I’ll discuss an article about cefepime vs piperacillin-tazobactam in adults hospitalized with acute infection.
Because piperacillin-tazobactam and cefepime have similar cost and coverage vs gram-negative bacteria, the choice of which agent to use in hospitalized patients with acute infection comes down to differences in adverse effect profiles. Patients who require empiric broad spectrum gram negative coverage also often require coverage against MRSA with vancomycin. Recent studies have suggested a link between increased rates of AKI when piperacillin-tazobactam is combined with vancomycin when compared with cefepime combined with vancomycin. However, other studies have examined a link between increased neurotoxicity with cefepime.
The ACORN randomized trial sought to compare rates of AKI and neurotoxicity in patients hospitalized with acute infection who were randomized 1:1 in an open-label fashion to receive either piperacillin-tazobactam or cefepime for gram-negative coverage. This trial was recently published in JAMA. Over 2500 patients were enrolled. The cefepime group received a 2-g intravenous push over 5 minutes every 8 hours and the piperacillin-tazobactam group received a 3.375-g bolus over 30 minutes for the initial administration followed by an extended infusion of 3.375 g every 8 hours infused over 4 hours for subsequent doses. Just over 77% of the trial population was also given vancomycin.
The primary outcome was a composite of the highest stage of AKI or death by day 14. The two secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.
There was no difference between groups in the primary outcome, and no difference between groups for the secondary outcome of major adverse kidney events at day 14. However, patients in the cefepime group had on average 0.3 fewer days alive and free of delirium and coma within 14 days when compared to the piperacillin-tazobactam group. This was statistically significant, with an odds ratio of 0.79.
In a separate analysis that included only the 1939 patients who also received vancomycin, piperacillin-tazobactam did not appear to affect the risk of AKI at any of the measured time points.
The authors concluded:
Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of AKI or death. Treatment with cefepime resulted in more neurological dysfunction.
This trial is not without weakness given that it was open-label, 20% of patients received at least 1 dose of the unassigned antibiotic, and the mean duration of therapy was short at only three days. Furthermore, the comparison involved the worst-case scenario with cefepime given that all doses were IV push and this administration technique has the highest rates of neurological side effects, and the best-case scenario with piperacillin-tazobactam given that the dose involved was the absolute lowest recommended for use in patients with acute illness. Given these caveats, this trial is the highest quality to date that does not suggest any increased risk of AKI with piperacillin-tazobactam when combined with vancomycin over cefepime.
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