Abstract: Background　As a serious global health problem, tuberculosis is the ninth cause of death. Tuberculous meningitis （TBM） is one of the most serious tuberculosis, and its current recommended treatment is 2HRZE/10HR. However. about half of patients with TBM were dead or disabled, with severe social harm. Linezolid （LZD） and levofloxacin （LFX） are second-line anti-tuberculosis drugs with strong anti-tuberculosis effect, and both have good blood-brain barrier permeability.Objective　To investigate the efficacy and side effects of LZD combined with LFX in the treatment of TBM during the intensive phrase of treatment.Methods 　We enrolled 49 cases who were diagnosed as definite，probable or possible TBM and received inpatient treatment from Huzhou Central Hospital from January 2014 to October 2017 and simply randomized them into the experimental group（n=24） and the control group（n=25），receiving the basic anti-TB treatment，basic anti-TB treatment combined with LZD and LFX，respectively.Examination of the cerebrospinal fluid （CSF） was performed at the baseline and end of the 1st，2nd，4th，8th weeks of treatment，white blood cell count （WBC），chloride and proteins，and glucose ratio （CSF/serum） were analyzed.The death，neurological sequelae and side effects associated with treatment were recorde between two groups at the end of the 8th week of treatment.Results　During the treatment period，the WBC and proteins decreased significantly but glucose ratio and chloride increased successively in the experimental group（P<0.05）．After the completion of 8-week treatment，the mortality rate and incidence of neurological sequelae were 8.0% （2/25），16.0% （4/24），respectively in the control group，and 4.2% （1/24），4.2% （1/24） respectively in the experimental group，indicating the two had similar rates of the death and neurological sequelae （χ2=1.203，P=0.273）．There was no significant difference in the incidence of adverse reactions between the two groups 〔56.0%（14/25） vs 66.7%（16/24），χ2=0.587，P=0.444）．Adverse reactionss associated with treatment occurred in both groups were not serious，and they were all relieved after the treatment was modified.Conclusion 　In the intensive phrase of treatment for TBM，basic anti-TB treatment combined with LZD and LFX can improve the outcome by promoting the recovery of CSF.

Key words: Tuberculosis, meningeal；Linezolid；Ofloxacin；Treatment outcome；Drug toxicity

摘要： 背景　结核病是严重的全球性问题，是全球第9大死因，结核性脑膜炎（TBM）是最严重的结核病之一，目前TBM的推荐治疗方案为2HRZE/10HR，但仍有约一半的TBM会导致死亡或残疾，危害严重；利奈唑胺（LZD）和左氧氟沙星（LFX）均是二线抗结核药物，抗结核作用强，同时两者均具有良好的血-脑脊液屏障渗透性。目的　探讨LZD联合LFX在TBM强化期应用的疗效和不良反应。方法　选取2014年1月—2017年10月在湖州市中心医院住院治疗的确诊TBM、很可能TBM、可能TBM患者共49例。采用简单随机法将患者分为试验组（24例）和对照组（25例）。对照组采用基础抗结核治疗方案；试验组在对照组的基础上，加用LZD和LFX。观察基线及治疗第1、2、4、8周的脑脊液（CSF）变化，包括白细胞计数、葡萄糖比值（CSF/血浆）、氯化物、蛋白定量。于治疗第8周记录死亡、神经系统后遗症及不良反应发生情况。结果　试验组第1周的白细胞计数、蛋白定量均低于基线，葡萄糖比值、氯化物均高于基线（P<0.05）；试验组第2周的白细胞计数、蛋白定量均低于第1周，葡萄糖比值、氯化物均高于第1周（P<0.05）；试验组第4周的白细胞计数、蛋白定量均低于第2周，葡萄糖比值、氯化物均高于第2周（P<0.05）；试验组第8周的白细胞计数、蛋白定量均低于第4周，葡萄糖比值、氯化物均高于第4周（P<0.05）。治疗第8周对照组死亡2例（8.0%），神经系统后遗症4例（16.0%），总发生率为24.0%（6/25）；试验组死亡1例（4.2%），神经系统后遗症1例（4.2%），总发生率为8.3%（2/24）。两组死亡和神经系统后遗症总发生率比较，差异无统计学意义（χ2=1.203，P=0.273）。两组患者不良反应发生率比较，差异无统计学意义〔56.0%（14/25）与66.7%（16/24），χ2=0.587，P=0.444〕。不良反应均在调整药物后好转，无严重不良反应发生。结论　TBM强化期在基础治疗的基础上加用LZD联合LFX治疗，可以促进CSF指标恢复，改善疾病预后，且并不增加不良反应。

关键词: 结核, 脑膜, LZD, 氧氟沙星, 治疗效果, 药物毒性