Individualized Treatment Effects of Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized with Acute Infection

IF 21.7 1区医学 Q1 CRITICAL CARE MEDICINE

American journal of respiratory and critical care medicine Pub Date : 2026-10-07 DOI:10.1093/ajrccm/aamag544

Edward T Qian,Emma J Graham Linck,Alexandra B Spicer,Kevin G Buell,Jonathan D Casey,Kevin P Seitz,Wesley H Self,Li Wang,Adam Wright,Todd W Rice,Matthew W Semler,Matthew M Churpek,for the Evidence-based Individualized Treatment Effects (EvITE) Group and the Pragmatic Critical Care Research Group

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Abstract

Abstract 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.

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头孢吡肟与哌拉西林-他唑巴坦在成人急性感染住院治疗中的个体化治疗效果

在急性感染住院的成年人中，最近的一项随机试验发现，头孢吡肟与哌拉西林-他唑巴坦对急性肾损伤或死亡的平均治疗效果不显著，但头孢吡肟的存活和无谵妄和昏迷天数更少。目的确定患者的个体特征是否会改变头孢吡肟与哌拉西林-他唑巴坦对预后的影响。方法对抗生素选择对肾脏预后的影响（ACORN）试验进行了二次分析，建立了一个效应模型，并对其进行了验证，以预测头孢吡肟与哌拉西林-他唑巴坦对急性感染住院成人的影响。主要终点是无急性肾损伤的生存期；次要结局是无谵妄或昏迷的生存。验证队列中预测的个体化治疗效果显著改善了头孢吡肟与哌拉西林-他唑巴坦对无急性肾损伤生存期的影响（Qini 1.68； 95%可信区间[CI]， 0.25-3.18； p值= 0.01）。在626名预计从头孢吡肟中获益≥5%的患者中，81.2%随机分配到头孢吡肟组的患者没有急性肾损伤，而74.2%随机分配到哌拉西林-他唑巴坦组（差异为7.1%;95%CI， 0.25至13.9%）。在203例预计哌拉西林-他唑巴坦获益≥5%的患者中，随机分配到头孢吡肟组的患者中有56.6%没有急性肾损伤，而随机分配到哌拉西林-他唑巴坦组的患者中有63.0%（差异为-6.3%;95%CI, -20.7至8.2%）。试验组对无谵妄或昏迷生存的影响不受个体特征的影响。结论患者的个体特征改变了头孢吡肟与哌拉西林-他唑巴坦对无急性肾损伤生存期的影响，但对无谵妄或昏迷生存期没有影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American journal of respiratory and critical care medicine 医学-呼吸系统

CiteScore

27.30

自引率

4.50%

发文量

1313

审稿时长

3-6 weeks

期刊介绍： The American Journal of Respiratory and Critical Care Medicine focuses on human biology and disease, as well as animal studies that contribute to the understanding of pathophysiology and treatment of diseases that affect the respiratory system and critically ill patients. Papers that are solely or predominantly based in cell and molecular biology are published in the companion journal, the American Journal of Respiratory Cell and Molecular Biology. The Journal also seeks to publish clinical trials and outstanding review articles on areas of interest in several forms. The State-of-the-Art review is a treatise usually covering a broad field that brings bench research to the bedside. Shorter reviews are published as Critical Care Perspectives or Pulmonary Perspectives. These are generally focused on a more limited area and advance a concerted opinion about care for a specific process. Concise Clinical Reviews provide an evidence-based synthesis of the literature pertaining to topics of fundamental importance to the practice of pulmonary, critical care, and sleep medicine. Images providing advances or unusual contributions to the field are published as Images in Pulmonary, Critical Care, Sleep Medicine and the Sciences. A recent trend and future direction of the Journal has been to include debates of a topical nature on issues of importance in pulmonary and critical care medicine and to the membership of the American Thoracic Society. Other recent changes have included encompassing works from the field of critical care medicine and the extension of the editorial governing of journal policy to colleagues outside of the United States of America. The focus and direction of the Journal is to establish an international forum for state-of-the-art respiratory and critical care medicine.