利奈唑胺片治疗结核性脑膜炎的临床研究

目的观察利奈唑胺片联合常规抗结核治疗方案治疗结核性脑膜炎(TBM)的临床疗效及安全性。方法将65例初治TBM患者随机分为对照组35例和试验组30例。对照组予以异烟肼片每次0.4~0.6 g,qd,口服+吡嗪酰胺片每次0.5 g,tid,口服+乙胺丁醇片每次0.75 g,qd,口服+利福平胶囊Ⅱ每次0.45~0.60 g,qd,口服,总抗结核治疗疗程为12~18个月;试验组在对照组治疗的基础上,予以利奈唑胺片每次600 mg,qd,口服(重度昏迷患者予以鼻饲给药),疗程6个月。比较2组患者的临床疗效和药物不良反应发生情况,并分析利奈唑胺药物谷浓度的变化情况。结果治疗后,试验组和对照组的总有效率分别为90.00%(27例/30例)和65.71%(23例/35例),差异有统计学意义(P<0.05)。2组患者在周围神经炎、肝功能损害、视神经炎、胃肠道不适、骨髓抑制等方面的药物不良反应发生率相似。利奈唑胺在通过血脑屏障到达脑脊液谷浓度值与血浆中谷浓度值之比方面,在TBM治疗前12周明显高于后期,此比值与脑脊液各项生化指标无明显相关性。结论利奈唑胺片联合常规抗结核治疗方案能显著改善初治TBM患者的临床症状,提高临床疗效,缩短治疗疗程,且安全性较高;利奈唑胺的应用疗程以12周为宜。

Clinical trial of linezolid tablets in the treatment of tuberculous meningitis

Objective To observe the clinical efficacy and safety of li-nezolid tablets combined with conventional anti-tuberculosis in the treatment of tuberculous meningitis(TBM). Methods Sixty-five patients with newly diagnosed TBM were randomly divided into control group(n=35 cases) and treatment group(n=30 cases). Control group was given isoniazid tablets 0.4-0.6 g each time, qd, orally+pyrazinamide tablets 0.5 g each time, tid, orally+ethambutol tablets 0.75 g each time, qd, orally+rifampicin capsules Ⅱ 0.45-0.60 g each time, qd, orally, total anti-tuberculosis treatment course was 12-18 months. On the basis of control group,the treatment group was added linezolid tablets 600 mg per time, qd, orally(severe coma patients with nasal feeding), the course of treatment was 6 months. The clinical efficacy and adverse drug reactions were compared between the two groups, and the changes of the concentration of linezolid drug were analyzed. Results After treatment, the total effective rates of treatment and control groups were 90.00%(27 cases/30 cases) and 65.71%(23 cases/35 cases) with significant difference(P<0.05). The incidences of peripheral neuritis,liver function damage,optic neuritis,gastrointestinal discomfort and myelosuppression were similar between two groups. The ratio of linezolid( cerebrospinal fluid trough concentration through blood-brain barrier vsplasma trough concentration) was significantly higher than that in the 12 weeks before TBM treatment than in the later period. There was no significant correlation between the ratio and the biochemical indicators of cerebrospinal fluid. Conclusion Linezolid tablets combined with conventional anti-tuberculosis treatment can significantly improve the clinical symptoms of patients with newly diagnosed TBM,improve clinical efficacy,shorten the course of treatment,and have higher safety.The treatment course of linezolid should be 12 weeks.