3 Key Takeaways
Plain English Summary- 01Core Finding
The primary outcome was survival without acute kidney injury; the secondary outcome was survival without delirium or coma.
- 02Study Evidence
Tested in a randomized controlled trial (626 patients) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
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.
The Discovery
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. To determine whether patients' individual characteristics modify the effect of cefepime versus piperacillin-tazobactam on outcomes. 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. 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; 9a clinically meaningful level confidence interval [CI], 0.25-3.18; p-value = 0.01). Among 626 patients predicted to experience ≥a clinically meaningful level 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%; 9a clinically meaningful levelCI, 0.25 to 13.9%). Among 203 patients predicted to experience ≥a clinically meaningful level 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%; 9a clinically meaningful levelCI, -20.7 to 8.2%). The effect of trial group on survival without delirium or coma was not modified by individual characteristics.
How It Works, Simply
This pulmonology research focuses on airway remodeling & alveolar gas-exchange pathway. Researchers evaluated it using a randomized controlled trial (626 patients) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
The primary outcome was survival without acute kidney injury; the secondary outcome was survival without delirium or coma.
- 02Study Evidence
Tested in a randomized controlled trial (626 patients) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (626 patients) · Randomized Clinical Trial
Biological Pathway & Modality
Airway remodeling & alveolar gas-exchange pathway
Intervention: Individualized Treatment Effects of Cefepime vs Piperacillin-Tazobactam in Adults
Experimental Findings & Endpoints
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.
To determine whether patients' individual characteristics modify the effect of cefepime versus piperacillin-tazobactam on outcomes. 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. 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; 9a clinically meaningful level confidence interval [CI], 0.25-3.18; p-value = 0.01).
Among 626 patients predicted to experience ≥a clinically meaningful level 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%; 9a clinically meaningful levelCI, 0.25 to 13.9%). Among 203 patients predicted to experience ≥a clinically meaningful level 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%; 9a clinically meaningful levelCI, -20.7 to 8.2%).
The effect of trial group on survival without delirium or coma was not modified by individual characteristics.
Clinical Translation & Practice Context
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.
The Bottom Line · Clinical Pearl
“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.”
Published in American Journal of Respiratory and Critical Care Medicine · Current Stage: Randomized Clinical Trial