Abstract：
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 1st 2016 and December 31st 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 using χ2 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), χ2=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, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.
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χ2检验和Mann-Whitney U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），χ2=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，χ2=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），χ2=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。.
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χ2检验和Mann-Whitney U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），χ2=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，χ2=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），χ2=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。.
摘要：
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