ACORN Analysis Suggests Patient Characteristics Modify Renal Outcomes With Cefepime Versus Piperacillin-Tazobactam

A secondary analysis of the Antibiotic Choice On Renal Outcomes (ACORN) randomized trial examined whether patient characteristics modified outcomes with cefepime versus piperacillin-tazobactam in adults hospitalized with acute infection. Investigators derived and validated an individualized treatment-effect model. The primary outcome was survival without acute kidney injury; the secondary outcome was survival without delirium or coma. The abstract did not report the total analysis population.

In the validation cohort, predicted individualized treatment effects significantly modified treatment effects on survival without acute kidney injury (Qini statistic, 1.68; 95% CI, 0.25–3.18; P=0.01). Among 626 patients predicted to benefit by at least 5% from cefepime, 81.2% assigned cefepime survived without acute kidney injury versus 74.2% assigned piperacillin-tazobactam (reported difference, 7.1 percentage points; 95% CI, 0.25–13.9). Among 203 patients predicted to benefit by at least 5% from piperacillin-tazobactam, corresponding proportions were 56.6% versus 63.0% (difference, −6.3 percentage points; 95% CI, −20.7 to 8.2).

Individual characteristics did not modify treatment effects on survival without delirium or coma. These findings suggest potential heterogeneity despite the original trial’s lack of a significant average effect on acute kidney injury or death. However, this was a secondary model-based analysis, the piperacillin-tazobactam-favored subgroup estimate was imprecise, and the abstract does not provide model inputs or implementation details. The results alone do not establish a bedside antibiotic-selection strategy.