一线抗结核药物联合利奈唑胺治疗儿童结核性脑膜炎的真实世界研究  

Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice

作　　者：艾婷 江莉[1] 刘泉波[1] 白媛 杨雅 孙凤军 贾运涛[2] 周玉姣 张祯祯[1] Ai Ting;Jiang Li;Liu Quanbo;Bai Yuan;Yang Ya;Sun Fengjun;Jia Yuntao;Zhou Yujiao;Zhang Zhenzhen(Department of Infectious Disease,Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity,Chongqing 401122,China;Department of Pharmacy,Children's Hospital of Chongqing Medical University,Chongqing 401122,China;Department of Pharmacy,the First Affiliated Hospital of Army Medical University,Chongqing 400038,China)

机构地区：[1]重庆医科大学附属儿童医院感染科、国家儿童健康与疾病临床医学研究中心、儿童发育疾病研究教育部重点实验室、儿童感染与免疫罕见病重庆市重点实验室,重庆401122 [2]重庆医科大学附属儿童医院药学部,重庆401122 [3]陆军军医大学附属第一医院药学部,重庆400038

出　　处：《中华儿科杂志》2024年第8期715-720,共6页Chinese Journal of Pediatrics

基　　金：重庆市卫健委中青年医学高端人才项目(2020GDRC003);重庆市首批公卫重点学科(渝财社[2023]121号)。

摘　　要：目的评估一线抗结核药物联合利奈唑胺治疗儿童非耐药结核性脑膜炎的效果及安全性。方法回顾性队列研究。选择2016年1月1日至2023年12月31日于重庆医科大学附属儿童医院感染科收治的89例非耐药结核性脑膜炎患儿为研究对象。根据初治用药方案分为一线抗结核药物[异烟肼、利福平、吡嗪酰胺、乙胺丁醇(HRZE)]组和HRZE联合利奈唑胺(HRZEL)组,比较两种方案的效果及安全性,并分析利奈唑胺药物浓度与不良反应的关系。采用χ^(2)检验和Mann-WhitneyU检验进行组间比较。结果89例非耐药的结核性脑膜炎患儿中,男53例、女36例,起病年龄4.6(1.4,9.6)岁。HRZEL组27例、HRZE组62例,治疗前HRZEL组干扰素阳性率低于HRZE组[64%(16/25)比92%(55/60),χ^(2)=9.82,P<0.05],脑脊液蛋白水平高于HRZE组[1.2(1.0,2.0)比0.8(0.4,1.4)g/L,Z=0.32,P<0.05]。强化期结束时,HRZEL组与HRZE组脑脊液蛋白、病原学阴转率比较差异均无统计学意义(均P>0.05)。44例高脑脊液蛋白(>1 g/L)患儿中,男25例、女19例,起病年龄6.7(3.0,11.8)岁,其中HRZEL组21例、HRZE组23例。治疗前HRZEL组与HRZE组干扰素阳性率和脑脊液蛋白水平比较差异均无统计学意义[62%(13/21)比87%(20/23),1.7(1.1,2.2)比1.5(1.2,1.9)g/L,χ^(2)=3.67、Z=0.23,均P>0.05]。强化期结束时,HRZEL组与HRZE组脑脊液蛋白水平、病原学阴转率和影像学缓解率比较差异均无统计学意义(均P>0.05)。HRZEL组粒细胞减少、胃肠道症状及停或换药发生率均高于HRZE组[44%(12/27)比19%(12/62),7%(2/27)比0,33%(9/27)比3%(2/62),χ^(2)=6.01、4.70、15.74,均P<0.05]。结论对于非耐药的儿童结核性脑膜炎,HRZEL方案在病原学阴转及脑脊液改善上的效果与HRZE方案接近。利奈唑胺治疗儿童结核性脑膜炎的过程中需密切监测药物不良反应。Objective:To evaluate the efficacy and safety of first-line anti-tuberculosis(TB)drugs combined with linezolid in treatment of children with tuberculous meningitis(TBM).Methods:A retrospective cohort study design was performed.Eight-nine Children diagnosed as TBM during January 1 st 2016 and December 31 st 2023 in Department of Infectious Disease,Children′s Hospital of Chongqing Medical University were enrolled in the study.According to different treatment regimens,children were divided into a group of first-line anti-tuberculous drugs(isoniazid,rifampicin,pyrazinamide,ethambutol(HRZE))and a group of HRZE and linezolid combination(HRZEL).The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed.Comparisons between groups were performed usingχ^(2) test and Mann-Whitney U test.Results:The 89 children with TBM included 53 males and 36 females with an onset age of 4.6(1.4,9.6)years.There were 27 cases in the HZREL group and 62 cases in the HRZE group.Before treatment,positive rate of interferon-gamma release assays(IGRA)in HRZEL group was lower than that in HRZE group(64%(16/25)vs.92%(55/60),χ^(2)=9.82,P<0.05),but protein level of cerebrospinal fluid(CSF)was higher than that in HRZE group(1.2(1.0,2.0)vs.0.8(0.4,1.4)g/L,Z=0.32,P<0.05).By the end of the intensive phase,there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group(both P>0.05).The 44 TBM children with high CSF protein(>1 g/L)included 25 males and 19 females with an onset age of 6.7(3.0,11.8)years.There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly.Before treatment,there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups(62%(13/21)vs.87%(20/23),1.7(1.1,2.2)vs.1.5(1.2,1.9)g/L,χ^(2)=3.67,Z=0.23,both P>0.05).There were no significant differences in CSF indicators,etiology negativity or imaging remission between the tw

关 键 词：儿童 结核 脑膜 抗结核药 不良反应 

分 类 号：R725.1[医药卫生—儿科]