Sudarsanam Thambu D, Rupali Priscilla, Tharyan Prathap, Abraham Ooriapadickal Cherian, Thomas Kurien
Medicine Unit 2 and Clinical Epidemiology Unit, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India, 632 004.
Cochrane Database Syst Rev. 2017 Jun 14;6(6):CD005437. doi: 10.1002/14651858.CD005437.pub4.
Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis.
To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease.
We searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017.
Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis.
Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach.
We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to 2.15; N = 477; 18 clinical failures; moderate-quality evidence), or neurological sequelae (RR 1.29, 95% CI 0.63 to 2.62; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae.
AUTHORS' CONCLUSIONS: We found no reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Moderate-quality evidence from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe, and economical in reducing serious outcomes. The choice between these antibiotics should be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justified in people with less severe illness, and are needed to provide reliable evidence in different clinical settings.
脑膜炎球菌病可在发病数小时内导致死亡或残疾。入院前使用抗生素旨在通过避免在确诊前延迟开始治疗来降低严重疾病和死亡风险。
研究入院前使用抗生素与不使用抗生素或安慰剂相比，以及不同的入院前抗生素治疗方案在降低疑似脑膜炎球菌病患者的死亡率、临床治疗失败率和发病率方面的有效性和安全性。
我们检索了Cochrane系统评价数据库（CENTRAL，截至2017年1月6日）、医学期刊数据库（MEDLINE，1966年至2017年1月6日）、荷兰医学文摘数据库（Embase，1980年至2017年1月6日）、科学引文索引（Web of Science，1985年至2017年1月6日）、拉丁美洲及加勒比地区卫生科学数据库（LILACS，1982年至2017年1月6日），以及截至2017年1月的前瞻性试验注册库。我们之前检索了1985年至2015年6月的CAB文摘数据库，但在2017年1月未更新该检索。
随机对照试验（RCT）或半随机对照试验，比较抗生素与安慰剂或不干预措施，针对疑似脑膜炎球菌感染患者，或比较入院前或确诊前使用不同抗生素的情况。
两位综述作者独立评估试验质量，并从检索结果中提取数据。我们计算了二分数据的风险比（RR）和95%置信区间（CI）。我们仅纳入了一项试验，因此未进行数据合成。我们使用GRADE方法评估证据的总体质量。
我们未找到比较入院前使用抗生素与不使用抗生素或安慰剂的随机对照试验。我们纳入了一项开放标签、非劣效性随机对照试验，该试验有510名参与者，在尼日尔的一次疫情期间进行，比较单次肌内注射头孢曲松与单次肌内注射长效（油性）氯霉素。在降低死亡率方面，头孢曲松不劣于氯霉素（RR 1.21，95%CI 0.57至2.56；N = 503；308例确诊为脑膜炎球菌性脑膜炎；26例死亡；中等质量证据）、临床治疗失败率（RR 0.83，95%CI 0.32至2.15；N = 477；18例临床治疗失败；中等质量证据）或神经后遗症发生率（RR 1.29，95%CI 0.63至2.62；N = 477；29例有后遗症；低质量证据）。未报告治疗的不良反应。估计治疗费用相似。没有关于后遗症所致疾病负担的数据。
我们未找到可靠证据支持对疑似非重症脑膜炎球菌病病例使用入院前抗生素。一项随机对照试验的中等质量证据表明，单次肌内注射头孢曲松和长效氯霉素在降低严重结局方面同样有效、安全且经济。这些抗生素之间的选择应基于可承受性、可获得性和抗生素耐药模式。对于病情较轻的患者，进一步比较不同入院前抗生素并辅以强化支持措施的随机对照试验在伦理上是合理的，并且需要在不同临床环境中提供可靠证据。
