Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection
JAMA, 2023 · Pragmatic randomized clinical trial (n=2,511).
Clinical question
Does cefepime vs piperacillin-tazobactam change the risk of acute kidney injury/death or neurologic dysfunction in hospitalized adults with acute infection?
What the trial found
Piperacillin-tazobactam did not increase AKI/death compared with cefepime in this randomized trial; cefepime had more neurologic dysfunction as a secondary outcome.
Current guideline position
Antibiotic selection should remain infection-, resistance-, allergy-, organ-function-, and neurotoxicity-risk specific rather than being driven by an assumed universal AKI difference between these two agents.
Clinical interpretation
Challenges the assumption that piperacillin-tazobactam is intrinsically more nephrotoxic than cefepime in all patients, while reinforcing attention to cefepime neurotoxicity, especially with renal dysfunction.
Life-threatening organ dysfunction caused by a dysregulated host response to infection — recognized by an acute rise in SOFA score, not by infection plus fever alone.
Molecular resistance mechanisms (ESBL, AmpC, KPC, NDM, OXA-48, DTR-Pseudomonas, CRAB), the MERINO trial, and modern novel beta-lactamase inhibitor therapeutics.
Sepsis-AKI microcirculatory decoupling, KDIGO staging, Furosemide Stress Test (FST), urine microscopy, and the AEIOU dialysis threshold framework.