Critical Care Medicine Department, National Institutes of Health, Bethesda, MD.
Critical Care Medicine Department, National Institutes of Health, Bethesda, MD.
Chest. 2019 Jun;155(6):1109-1118. doi: 10.1016/j.chest.2018.12.029. Epub 2019 Feb 14.
Procalcitonin (PCT)-guided antibiotic discontinuation appears to decrease antibiotic use in critically ill patients, but its impact on survival remains less certain.
We searched PubMed, Embase, Scopus, Web of Science, and CENTRAL for randomized controlled trials (RCTs) of PCT-guided antibiotic discontinuation in critically ill adults reporting survival or antibiotic duration. Searches were conducted without language restrictions from inception to July 23, 2018. Two reviewers independently conducted all review stages; another adjudicated differences. Data were pooled using random-effects meta-analysis. Study quality was assessed with the Cochrane risk of bias tool, and evidence was graded using GRADEpro.
Among critically ill adults (5,158 randomized; 5,000 analyzed), PCT-guided antibiotic discontinuation was associated with decreased mortality (16 RCTs; risk ratio [RR], 0.89; 95% CI, 0.83-0.97; I = 0%; low certainty). Death was the primary outcome in only one study and a survival benefit was not observed in the subset specified as sepsis (10 RCTs; RR, 0.94; 95% CI, 0.85-1.03; I = 0%), those without industry sponsorship (nine RCTs; RR, 0.98; 95% CI, 0.87-1.10; I = 0%), high PCT-guided algorithm adherence (five RCTs; RR, 0.93; 95% CI, 0.71-1.22; I = 0%), and PCT-guided algorithms without C-reactive protein (eight RCTs; RR, 0.96; 95% CI, 0.87-1.06; I = 0%). PCT-guided antibiotic discontinuation decreased antibiotic duration (mean difference, 1.31 days; 95% CI, -2.27 to -0.35; I = 93%) (low certainty).
Our findings of increased survival and decreased antibiotic utilization associated with PCT-guided antibiotic discontinuation represent low-certainty evidence with a high risk of bias. This relationship was primarily observed in studies without high protocol adherence and in studies with algorithms combining PCT and C-reactive protein. Properly designed studies with mortality as the primary outcome are needed to address this question.
International Prospective Register of Systematic Reviews (PROSPERO); No.: CRD42016049715; URL: http://www.crd.york.ac.uk/PROSPERO_REBRANDING/display_record.asp?ID=CRD42016049715.
降钙素原 (PCT)-指导的抗生素停药似乎可以减少危重症患者的抗生素使用，但对生存的影响仍不确定。
我们检索了 PubMed、Embase、Scopus、Web of Science 和 CENTRAL 中关于 PCT 指导的危重症成人抗生素停药的随机对照试验 (RCT)，报告了生存或抗生素持续时间。检索没有语言限制，从开始到 2018 年 7 月 23 日。两名审查员独立进行了所有审查阶段；另一名则对分歧进行了裁决。使用随机效应荟萃分析对数据进行汇总。使用 Cochrane 偏倚风险工具评估研究质量，并使用 GRADEpro 对证据进行分级。
在危重症成人中（5158 名随机分配；5000 名分析），PCT 指导的抗生素停药与死亡率降低相关（16 项 RCT；风险比 [RR]，0.89；95%CI，0.83-0.97；I = 0%；低确定性）。只有一项研究将死亡作为主要结局，并且在指定为败血症的亚组（10 项 RCT；RR，0.94；95%CI，0.85-1.03；I = 0%）、没有行业赞助的亚组（9 项 RCT；RR，0.98；95%CI，0.87-1.10；I = 0%）、高 PCT 指导算法依从性的亚组（5 项 RCT；RR，0.93；95%CI，0.71-1.22；I = 0%）和不使用 C 反应蛋白的 PCT 指导算法的亚组（8 项 RCT；RR，0.96；95%CI，0.87-1.06；I = 0%）中未观察到生存获益。PCT 指导的抗生素停药缩短了抗生素持续时间（平均差异，1.31 天；95%CI，-2.27 至 -0.35；I = 93%）（低确定性）。
我们发现，与 PCT 指导的抗生素停药相关的生存增加和抗生素使用减少，代表了具有高偏倚风险的低确定性证据。这种关系主要存在于不遵守高方案的研究中，以及将 PCT 和 C 反应蛋白结合起来的算法的研究中。需要设计适当的以死亡率为主要结局的研究来解决这个问题。
国际前瞻性系统评价注册库（PROSPERO）；编号：CRD42016049715；网址：http://www.crd.york.ac.uk/PROSPERO_REBRANDING/display_record.asp?ID=CRD42016049715。
