Vermeij Jan-Dirk, Westendorp Willeke F, Dippel Diederik Wj, van de Beek Diederik, Nederkoorn Paul J
Department of Neurology, Academic Medical Centre, University of Amsterdam, PO Box 22660, Amsterdam, Netherlands, 1100 DD.
Cochrane Database Syst Rev. 2018 Jan 22;1(1):CD008530. doi: 10.1002/14651858.CD008530.pub3.
Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review.
To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms.
We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field.
Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke.
Two review authors independently selected articles and extracted data; we discussed and resolved discrepancies at a consensus meeting with a third review author. We contacted study authors to obtain missing data when required. An independent review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity amongst included studies, and performed subgroup analyses on study quality.
We included eight studies involving 4488 participants. Regarding quality of evidence, trials showed differences in study population, study design, type of antibiotic, and definition of infection; however, primary outcomes among the included studies were consistent. Mortality rate in the preventive antibiotic group was not significantly different from that in the control group (373/2208 (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high-quality evidence). The number of participants with a poor functional outcome (death or dependency) in the preventive antibiotic therapy group was also not significantly different from that in the control group (1158/2168 (53%) vs 1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate-quality evidence). However, preventive antibiotic therapy did significantly reduce the incidence of 'overall' infections in participants with acute stroke from 26% to 19% (408/2161 (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high-quality evidence). This finding was highly significant for urinary tract infections (81/2131 (4%) vs 204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high-quality evidence), whereas no preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR 0.95, 95% CI 0.80 to 1.13; high-quality evidence). No major side effects of preventive antibiotic therapy were reported. Only two studies qualitatively assessed the occurrence of elevated body temperature; therefore, these results could not be pooled. Only one study reported length of hospital stay.
AUTHORS' CONCLUSIONS: Preventive antibiotics had no effect on functional outcome or mortality, but significantly reduced the risk of 'overall' infections. This reduction was driven mainly by prevention of urinary tract infection; no effect for pneumonia was found.
在高收入国家，中风是导致残疾的主要原因，在全球范围内是第二大致死原因。中风后感染频繁发生，可能对预后产生不利影响。中风急性期的预防性抗生素治疗可能会降低感染发生率并改善预后。在本Cochrane系统评价的上一版（2012年发表）中，我们发现抗生素确实降低了感染风险，但并未减少依赖或死亡患者的数量。然而，纳入的研究规模较小且异质性较大。2015年，两项大型临床试验发表，因此有必要对本系统评价进行更新。
评估预防性抗生素治疗对缺血性或出血性中风患者的有效性和安全性。我们希望确定急性中风患者的预防性抗生素治疗是否：
•降低随访时功能预后不良（依赖和/或死亡）的风险；
•降低中风急性期感染的发生率；
•降低中风急性期体温升高（体温≥38°C）的发生率；
•缩短住院时间；
•导致严重不良事件发生率增加，如过敏性休克、皮疹或抗生素耐药微生物定植。
我们检索了Cochrane中风组试验注册库（2017年6月25日）；Cochrane图书馆中的Cochrane对照试验中心注册库（CENTRAL；2017年第5期；2017年6月25日）；MEDLINE Ovid（1950年至2017年5月11日）以及Embase Ovid（1980年至2017年5月11日）。为了识别更多已发表、未发表和正在进行的试验，我们检索了试验和研究注册库，浏览了参考文献列表，并联系了该领域的试验作者、同事和研究人员。
急性缺血性或出血性中风患者预防性抗生素治疗与对照（安慰剂或开放对照）的随机对照试验（RCT）。
两名综述作者独立选择文章并提取数据；我们在与第三位综述作者的共识会议上讨论并解决了分歧。必要时，我们联系研究作者以获取缺失数据。一名独立的综述作者使用Cochrane“偏倚风险”工具评估偏倚风险。我们计算了二分结局的风险比（RRs），评估了纳入研究之间的异质性，并对研究质量进行了亚组分析。
我们纳入了八项研究，涉及4488名参与者。关于证据质量，试验在研究人群、研究设计、抗生素类型和感染定义方面存在差异；然而，纳入研究的主要结局是一致的。预防性抗生素组的死亡率与对照组无显著差异（373/2208（17%）对360/2214（1
