American journal of respiratory and critical care medicine · 2026
Individualized Treatment Effects of Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized with Acute Infection.
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Qian Edward T, Graham Linck Emma J, Spicer Alexandra B, Buell Kevin G, Casey Jonathan D, Seitz Kevin P, Self Wesley H, Wang Li, Wright Adam, Rice Todd W, Semler Matthew W, Churpek Matthew M, Evidence-based Individualized Treatment Effects (EvITE) Group and the Pragmatic Critical Care Research Group
Аннотация
RATIONALE: Among adults hospitalized with acute infection, a recent randomized trial observed no significant average treatment effect of cefepime versus piperacillin-tazobactam on acute kidney injury or death, but fewer days-alive-and-free-of delirium and coma with cefepime.
OBJECTIVES: To determine whether patients' individual characteristics modify the effect of cefepime versus piperacillin-tazobactam on outcomes.
METHODS: In this secondary analysis of the Antibiotic Choice On Renal Outcomes (ACORN) trial, an effect model was derived and validated to predict the effect of cefepime versus piperacillin-tazobactam for adults hospitalized with acute infection. The primary outcome was survival without acute kidney injury; the secondary outcome was survival without delirium or coma.
MEASUREMENTS AND MAIN RESULTS: The individualized treatment effect predicted in the validation cohort significantly modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury (Qini 1.68; 95% confidence interval [CI], 0.25-3.18; p-value = 0.01). Among 626 patients predicted to experience ≥5% benefit from cefepime, 81.2% of patients randomized to cefepime survived without acute kidney injury, versus 74.2% randomized to piperacillin-tazobactam (difference, 7.1%; 95%CI, 0.25 to 13.9%). Among 203 patients predicted to experience ≥5% benefit from piperacillin-tazobactam, 56.6% of patients randomized to cefepime survived without acute kidney injury, versus 63.0% randomized to piperacillin-tazobactam (difference, -6.3%; 95%CI, -20.7 to 8.2%). The effect of trial group on survival without delirium or coma was not modified by individual characteristics.
CONCLUSIONS: Patients' individual characteristics modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury but not on survival without delirium or coma.
OBJECTIVES: To determine whether patients' individual characteristics modify the effect of cefepime versus piperacillin-tazobactam on outcomes.
METHODS: In this secondary analysis of the Antibiotic Choice On Renal Outcomes (ACORN) trial, an effect model was derived and validated to predict the effect of cefepime versus piperacillin-tazobactam for adults hospitalized with acute infection. The primary outcome was survival without acute kidney injury; the secondary outcome was survival without delirium or coma.
MEASUREMENTS AND MAIN RESULTS: The individualized treatment effect predicted in the validation cohort significantly modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury (Qini 1.68; 95% confidence interval [CI], 0.25-3.18; p-value = 0.01). Among 626 patients predicted to experience ≥5% benefit from cefepime, 81.2% of patients randomized to cefepime survived without acute kidney injury, versus 74.2% randomized to piperacillin-tazobactam (difference, 7.1%; 95%CI, 0.25 to 13.9%). Among 203 patients predicted to experience ≥5% benefit from piperacillin-tazobactam, 56.6% of patients randomized to cefepime survived without acute kidney injury, versus 63.0% randomized to piperacillin-tazobactam (difference, -6.3%; 95%CI, -20.7 to 8.2%). The effect of trial group on survival without delirium or coma was not modified by individual characteristics.
CONCLUSIONS: Patients' individual characteristics modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury but not on survival without delirium or coma.