University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia.
JAMA. 2024 Aug 27;332(8):638-648. doi: 10.1001/jama.2024.9803.
There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock.
To determine whether prolonged β-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions.
The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024.
Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of β-lactam antibiotics in critically ill adults with sepsis or septic shock.
Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach.
The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure.
From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of β-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty).
Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock.
PROSPERO Identifier: CRD42023399434.
目前尚不确定延长β-内酰胺类抗生素输注时间是否能改善脓毒症或感染性休克的危重症成人患者的临床重要结局。
旨在确定与间歇性输注相比，延长β-内酰胺类抗生素输注时间是否会降低危重症成人脓毒症或感染性休克患者的死亡风险。
主要检索了 MEDLINE（通过 PubMed）、CINAHL、Embase、Cochrane 对照试验中心注册库（CENTRAL）和 ClinicalTrials.gov，检索时间截至 2024 年 5 月 2 日。
比较延长（持续或延长）和间歇性输注β-内酰胺类抗生素在脓毒症或感染性休克的危重症成人患者中的疗效的随机临床试验。
由两名评审员独立进行数据提取和偏倚评估。使用推荐评估、制定与评估分级方法评估证据确定性。贝叶斯框架被用作主要分析方法，而频率论框架被用作次要方法。
主要结局为全因 90 天死亡率。次要结局包括 ICU 死亡率和临床治愈率。
从 18 项纳入了 9108 例脓毒症或感染性休克的危重症成人患者（中位年龄 54 岁，IQR 48-57；5961 例男性[65%]）的合格随机临床试验中，17 项试验（9014 名参与者）提供了主要结局的数据。与间歇性输注相比，延长β-内酰胺类抗生素输注时间的全因 90 天死亡率的估计风险比为 0.86（95%可信区间，0.72-0.98；I2=21.5%；高确定性），99.1%的后验概率表明延长输注与较低的 90 天死亡率相关。延长β-内酰胺类抗生素输注与 ICU 死亡率降低相关（风险比，0.84；95%可信区间，0.70-0.97；高确定性），且临床治愈率增加（风险比，1.16；95%可信区间，1.07-1.31；中等确定性）。
在 ICU 中的患有脓毒症或感染性休克的成年人中，与间歇性输注相比，使用延长β-内酰胺类抗生素输注时间与降低 90 天死亡率相关。目前的证据为临床医生提供了高度确定性，认为延长输注可以作为脓毒症和感染性休克管理的标准治疗方法。
PROSPERO 标识符：CRD42023399434。
