SIS Study of Aggressive versus Conservative Antimicrobial Initiation in the ICU

描述(由申请人提供)：拟议的计划拨款和研究的目标是通过证明在客观数据返回之前不使用抗生素对疑似重症患者是安全和有效的，从而减少危重患者不必要的抗菌药的使用。 有感染而没有败血症休克的。基于之前的试点研究，启动的两个策略 ICU患者的抗菌药将进行比较：一旦怀疑感染，就开始使用抗生素，或者等到早期培养数据返回，确认感染。其具体目标是：1)确定接受每种策略治疗的患者中与感染相关的死亡率；2)确定感染率、使用抗菌药物的总天数和感染率。 3)确定临床代谢组模型的有效性，以预测哪些脓毒症患者实际存在感染以及感染患者的死亡率，从而识别可能受益于积极的抗菌素治疗的高危患者。该提案是为了进行一项六中心、整群随机、方案交叉、务实、非盲目、比较有效性的试验，以评估两种策略在治疗疑似新发ICU获得性感染的危重手术患者中的等效性。据估计，在ICU接受治疗的8500名患者的基线感染相关死亡率为15%。威力分析表明，这一样本量将足以证明两种策略在感染相关死亡率方面的等价性，并足以表明保守治疗组的抗菌药使用量显著减少。此外，将对一部分患者进行血浆脂肪酸代谢物分析，以前瞻性地识别感染和死亡风险特别高的患者。如果在感染复发的客观证据不会恶化结果的情况下停止使用抗菌药，在高度脆弱的危重患者中可能会有益地减少至少25%的抗菌药使用。

DESCRIPTION (provided by applicant): The goal of the proposed planning grant and study is to reduce the use of unnecessary antimicrobials in critically ill patients by demonstrating that withholding antibiotics until objective data returns is safe and effective in patients suspected of having an infection without septic shock. Based on a prior pilot study, two strategies for starting antimicrobial agents in patients in the ICU will be compared: Starting antibiotics as soon as an infection is suspected or waiting until early culture data returns confirming an infection. The specific aims are to 1) Determine the infection-related mortality in patients treated with each strategy, 2) Determine the rates of infection, total number of days of antimicrobial use, and rates of secondary infections with multidrug resistant organisms, 3) Determine the utility of a clinico- metabolomic models to predict which septic patients actually harbor infection and the mortality in infected patients, identifying high-risk patients that could benefit from aggressive antimicrobil therapy. The proposal is for a six-center, cluster-randomized, protocol crossover, pragmatic, unblinded, comparative effectiveness trial of the equivalence of two strategies in the management of critically ill surgical patients suspected of having a new-onset, ICU-acquired infection. An estimated 8,500 patients treated in ICUs will be followed with a baseline infection-related mortality of 15%. Power analysis suggests that this sample size will be adequate to demonstrate equivalence between the two strategies in terms of infection-related mortality, and sufficient to show significant decreases in antimicrobial usage in the conservative treatment group. In addition, a subset of patients will have plasma fatty acid metabolites analyzed to prospectively identify patients at particularly high risk of infection and death. If withholding antimicrobials until objective evidence of infection returns can be performed without worsening outcomes, a beneficial reduction of antimicrobial use of at least 25% may be possible among highly vulnerable, critically ill patients.