Giolito Anna, Levy Corinne, Varon Emmanuelle, Cohen Robert, Hanna Sidonie, Assad Zein, Lenglart Léa, Bechet Stephane, Bonacorsi Stephane, Dubos François, Launay Elise, Pelleter Morgane, Rybak Alexis, Angoulvant Francois, Levy Michael, Ouldali Naïm
Department of General Paediatrics, Paediatric Infectious Disease and Internal Medicine, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.
Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France; IMRB-GRC GEMINI, Centre Hospitalier Intercommunal, Research Centre, Université Paris Est, Créteil, France; French Group of Paediatric Infectious Diseases, Paris, France.
Lancet Child Adolesc Health. 2025 Apr;9(4):255-261. doi: 10.1016/S2352-4642(25)00029-X.
Pneumococcal meningitis is a leading cause of bacterial meningitis and the most deadly pneumococcal disease in children worldwide. There is a paucity of evidence concerning the benefit of dexamethasone to prevent death in paediatric pneumococcal meningitis. We aimed to compare the effect of early adjunctive therapy with dexamethasone versus no dexamethasone on death in children with pneumococcal meningitis.
We did a non-randomised, comparative, multicentre, retrospective, quasi-experimental, propensity score-based study using data from a French national surveillance system of pneumococcal meningitis in children that collates data for 238 French paediatric wards working with 168 microbiology laboratories. We compared outcomes of adjunctive therapy with dexamethasone treatment (0·15 mg/kg every 6 h, for 4 days, per national guidelines) given within 12 h of antibiotic treatment versus no dexamethasone among all children aged 0-17 years with confirmed pneumococcal meningitis who had been hospitalised in one of the participating centres between Jan 1, 2005, and Nov 1, 2022. The primary outcome was 30-day all-cause death after hospital admission. The main propensity score analysis was based on inverse probability treatment weighting (IPTW), allowing adjustment for initial severity and baseline characteristics. Sensitivity analyses, such as propensity score matching, were done to assess the robustness of the results.
Between Jan 1, 2005, and Nov 1, 2022, 1765 cases of pneumococcal meningitis were reported to the National Surveillance System of Paediatric Bacterial Meningitis. 534 were excluded from the analysis and 1231 were included, with a median age of 1·1 years (IQR 0·5-5·0, range 0-17·9). 495 (40%) of 1231 patients were female, 716 (58%) were male, and 20 (1%) were missing data for sex. 650 (53%) of 1231 children received dexamethasone and 581 (47%) children did not receive dexamethasone. 108 (9%) of 1231 patients died. Within 30 days of hospitalisation, 105 (9%) patients died, 36 (6%) of 650 in the dexamethasone group and 69 (12%) of 581 in the no dexamethasone group. After IPTW, the adjusted 30-day death rate was 6% in the dexamethasone group and 12% in the no dexamethasone group (marginal odds ratio 0·39, 95% CI 0·23-0·65). All sensitivity analyses gave similar results.
Adjunctive dexamethasone within 12 h of starting antibiotic treatment was associated with a reduced 30-day risk of death in children hospitalised with pneumococcal meningitis. Our findings support the use of dexamethasone to reduce the risk of death in paediatric pneumococcal meningitis.
Pfizer, ACTIV, and National Institute of Health and Medical Research (Inserm) Centre.
肺炎球菌性脑膜炎是细菌性脑膜炎的主要病因，也是全球儿童中最致命的肺炎球菌疾病。关于地塞米松预防小儿肺炎球菌性脑膜炎死亡的益处，证据不足。我们旨在比较早期辅助使用地塞米松与不使用地塞米松对肺炎球菌性脑膜炎患儿死亡的影响。
我们进行了一项非随机、比较性、多中心、回顾性、准实验性、基于倾向评分的研究，使用来自法国全国儿童肺炎球菌性脑膜炎监测系统的数据，该系统整理了与168个微生物实验室合作的238个法国儿科病房的数据。我们比较了在抗生素治疗12小时内给予地塞米松治疗（按照国家指南，每6小时0.15mg/kg，共4天）的辅助治疗结果与所有确诊为肺炎球菌性脑膜炎、年龄在0至17岁之间、于2005年1月1日至2022年11月1日期间在参与中心之一住院的儿童中不使用地塞米松的结果。主要结局是入院后30天全因死亡。主要倾向评分分析基于逆概率处理加权（IPTW），允许对初始严重程度和基线特征进行调整。进行了倾向评分匹配等敏感性分析以评估结果的稳健性。
在2005年1月1日至2022年11月1日期间，全国小儿细菌性脑膜炎监测系统报告了1765例肺炎球菌性脑膜炎病例。534例被排除在分析之外，1231例被纳入，中位年龄为1.1岁（四分位间距0.5 - 5.0，范围0 - 17.9）。1231例患者中，495例（40%）为女性，716例（58%）为男性，20例（1%）性别数据缺失。1231例儿童中，650例（53%）接受了地塞米松，581例（47%）未接受地塞米松。1231例患者中有108例（9%）死亡。在住院30天内，105例（9%）患者死亡，地塞米松组650例中有36例（6%），未使用地塞米松组581例中有69例（12%）。经过IPTW后，地塞米松组调整后的30天死亡率为6%，未使用地塞米松组为12%（边际优势比0.39，95%置信区间0.23 - 0.65）。所有敏感性分析均得出相似结果。
在开始抗生素治疗12小时内辅助使用地塞米松与肺炎球菌性脑膜炎住院患儿30天死亡风险降低相关。我们的研究结果支持使用地塞米松降低小儿肺炎球菌性脑膜炎的死亡风险。
辉瑞公司、ACTIV和国家卫生与医学研究机构（Inserm）中心。
