Maryland survey finds high prevalence of worrisome pathogens in mechanically ventilated patients

The results of a randomized trial answer some important questions regarding the comparative safety of two antibiotics used for empiric treatment of adults hospitalized with acute infection, researchers reported late last week in JAMA.

In the Antibiotic Choice on Renal Outcomes (ACORN) trial, investigators with Vanderbilt University Medical Center compared cefepime with piperacillin-tazobactam in adults prescribed antipseudomonal antibiotics within 12 hours of presentation to the emergency department or medical intensive care unit. While both drugs have similar activity against gram-negative bacteria, some observational studies have reported an association between piperacillin-tazobactam and acute kidney injury (AKI), while others have suggested links between cefepime and neurotoxicity.

Patients were enrolled and randomized 1:1 to receive either drug from November 10, 2021, to October 7, 2022. The primary outcome was AKI, measured on a five-level ordinal scale, or death by day 15. Secondary outcomes included incidence of major adverse kidney events at day 14 and number of days alive and free of delirium and coma within 14 days.

Cefepime patients see increase in neurologic dysfunction

Among the 2,511 patients (median age, 58 years; 42.7% female) included in the primary analysis, the highest stage of AKI or death was not significantly different between the cefepime group and the piperacillin-tazobactam group. There were 85 patients (7%) with stage 3 AKI and 92 (7.6%) who died in the cefepime group, compared with 97 patients (7.5%) with stage 3 AKI and 78 (6%) who died in the piperacillin-tazobactam group (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.80 to 1.13).

The incidence of major adverse kidney events at day 14 did not differ between the cefepime group (10.2%) and the piperacillin-tazobactam group (8.8%; absolute difference, 1.4%; 95% CI, −1.0% to 3.8%).

However, patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days than those in the piperacillin-tazobactam group (mean, 11.9 days vs 12.2 days; OR, 0.79; 95% CI, 0.65 to 0.95).

“Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of AKI or death,” the study authors concluded. “Treatment with cefepime resulted in more neurological dysfunction.”

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