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[Lancet Infect Dis最新论文]:延长与短时静脉输注抗假单胞菌β-内酰胺抗生素治疗全身性感染患者:RCT的系统回顾与meta分析
2018年01月14日 时讯速递, 进展交流 暂无评论

Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials

Konstantinos Z Vardakas, Georgios L Voulgaris, Athanasios Maliaros, et al

Lancet Infect Dis 2018; 18: 108-20

Published Online October 25, 2017

http://dx.doi.org/10.1016/S1473-3099(17)30615-1

Summary

Background 背景

The findings of randomised controlled trials (RCT), observational studies, and meta-analyses vary regarding the effectiveness of prolonged β-lactam infusion. We aimed to identify the effectiveness of prolonged versus short-term infusion of antipseudomonal β-lactams in patients with sepsis.

有关延长β-内酰胺抗生素输注时间的疗效,随机对照试验(RCT)、观察性研究以及meta分析的结果各异。我们希望明确延长输注与短时输注抗假单胞菌β-内酰胺抗生素对全身性感染患者的疗效。

Methods 方法

We did a systematic review and meta-analysis to compare prolonged versus short-term intravenous infusion of antipseudomonal β-lactams in patients with sepsis. Two authors independently searched PubMed, Scopus, and the Cochrane Library of clinical trials until November, 2016, without date or language restrictions. Any RCT comparing mortality or clinical efficacy of prolonged (continuous or ≥3 h) versus short-term (≤60 min) infusion of antipseudomonal β-lactams for the treatment of patients with sepsis was eligible. Studies were excluded if they were not RCTs, the antibiotics in the two arms were not the same, neither mortality nor clinical efficacy was reported, only pharmacokinetic or pharmacodynamic outcomes were reported, or if ten or fewer patients were enrolled or randomised. Data were extracted in prespecified forms and we then did a meta-analysis using a Mantel-Haenszel random-effects model. The primary outcome was all-cause mortality at any timepoint. This meta-analysis is registered with the PROSPERO database, number CRD42016051678, and is reported according to PRISMA guidelines.

我们进行了系统回顾与meta分析,以比较延长与短时静脉输注抗假单胞菌β-内酰胺抗生素对全身性感染患者的疗效。2名作者独立检索了至2016年11月的PubMed, Scopus, and the Cochrane Library of clinical trials,没有日期及语言限制。任何比较延长(持续或≥3 h)与短时(≤60分钟)输注抗假单胞菌β-内酰胺抗生素治疗全身性感染患者的病死率或临床疗效的研究均可入选。排除标准包括非RCT,两组患者使用抗生素不同,没有报告病死率及临床疗效,仅报告药代动力学或药效学结局,或入选患者不超过10名。我们根据预先设计的表格获取数据,并采用Mantel-Haenszel随机效应模型进行meta分析。主要预后指标为任何时间点的全因病死率。这一meta分析在 PROSPERO 数据库注册,注册号 CRD42016051678,并根据 PRISMA 指南报告结果。

Findings 结果

2196 articles were identified and screened, and 22 studies (1876 patients) were included in the meta-analysis. According to the Grading of Recommendations Assessment, Development, and Evaluation tool, the quality of evidence for mortality was high. Carbapenems, penicillins, and cephalosporins were studied. Patients with variable age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, severity of sepsis and renal function were enrolled. Prolonged infusion was associated with lower all-cause mortality than short-term infusion (risk ratio [RR] 0.70, 95% CI 0.56–0.87). Heterogeneity was not observed (p=0.93, IÇ=0%). The funnel plot and the Egger’s test (p=0.44) showed no evidence of publication bias.

检索并筛选2196篇文章,最终22项研究(1876名患者)纳入meta分析。根据GRADE工具,有关病死率的证据质量很高。研究用药包括碳青霉烯、青霉素及头孢菌素。不同年龄、APACHE II评分、全身性感染严重程度及肾脏功能状态的患者入选。与短时输注相比,延长输注伴随全因病死率降低 (风险比[RR] 0.70, 95% CI 0.56–0.87)。未观察到异质性 (p=0.93, IÇ=0%). 漏斗图及Egger检验(p=0.44) 未发现发表偏倚的证据。

Interpretation 结论

Prolonged infusion of antipseudomonal β-lactams for the treatment of patients with sepsis was associated with significantly lower mortality than short-term infusion. Further studies in specific subgroups of patients according to age, sepsis severity, degree of renal dysfunction, and immunocompetence are warranted.

与短时输注相比,延长输注抗假单胞菌β-内酰胺抗生素伴随全身性感染患者病死率降低。需要对不同年龄、全身性感染严重程度、肾脏功能不全成都及免疫功能状态进行进一步研究。

Funding 资助

None.

 

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