For empiric treatment of acute infection in hospitalized adults, piperacillin-tazobactam did not increase the incidence of acute kidney injury or death, but cefepime resulted in more neurological dysfunction, a study shows.
The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial included adults with orders for antipseudomonal antibiotics within 12 hours of presentation to the emergency department or medical intensive care unit of a U.S. academic medical center between Nov. 10, 2021, and Oct. 7, 2022. Participants were randomized to cefepime or piperacillin-tazobactam, with these effects on a primary outcome of the highest stage of acute kidney injury or death by day 14: “There were 2,511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1,214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1,297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, −1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).”
Editorial: “The trial design facilitated rapid enrollment for a traditionally difficult to enroll population by embedding the trial within routine care,” editorialists write. “This should be applauded. [These authors] provide a roadmap for such embedded randomized clinical trials for empirical antibiotic treatment of sepsis. The current study could be replicated using almost identical processes at multiple hospitals. Now, the question of whether antibiotics with antipseudomonal activity are even required for community-acquired and low-acuity sepsis can be addressed.”