Ellard G A, Humphries M J, Allen B W
National Institute for Medical Research, London, United Kingdom.
Am Rev Respir Dis. 1993 Sep;148(3):650-5. doi: 10.1164/ajrccm/148.3.650.
Tuberculous meningitis is a very serious form of tuberculosis. In the absence of randomized controlled trials of alternative treatment regimens, its management depends on employing potent drugs that penetrate well into the cerebrospinal fluid (CSF). The penetration of isoniazid, rifampin, and streptomycin into the CSF of 27 Chinese patients was studied using fluorimetric and microbiologic procedures. Isoniazid rapidly diffused into the CSF, peak concentrations in excess of 3 mg/L, or over 30 times its minimal inhibitory concentration (MIC) against Mycobacterium tuberculosis being attained within 4 hr. In contrast, rifampin and streptomycin penetrated very slowly across the meninges, and CSF levels only slightly in excess of their MICs against M. tuberculosis were achieved. The penetration of the drugs into the CSF correlated poorly with differences in their partitioning between octanol/water and cyclohexane/water but could be predicted using a simple model based on their renal clearance rates and plasma protein binding. It is recommended that patients with tuberculous meningitis should be treated for at least 9 months with a combination of isoniazid, rifampin, and pyrazinamide, which may be supplemented in the first 2 mo with streptomycin.
结核性脑膜炎是一种非常严重的结核病形式。在缺乏替代治疗方案的随机对照试验的情况下，其治疗依赖于使用能很好地渗透到脑脊液（CSF）中的强效药物。采用荧光法和微生物学方法研究了异烟肼、利福平及链霉素在27例中国患者脑脊液中的渗透情况。异烟肼能迅速扩散至脑脊液中，4小时内即可达到超过3mg/L的峰值浓度，即超过其对结核分枝杆菌最低抑菌浓度（MIC）的30倍以上。相比之下，利福平和链霉素透过脑膜的速度非常缓慢，脑脊液中的浓度仅略高于其对结核分枝杆菌的MIC。药物向脑脊液中的渗透与其在正辛醇/水和环己烷/水之间的分配差异相关性较差，但可使用基于其肾脏清除率和血浆蛋白结合率的简单模型进行预测。建议结核性脑膜炎患者使用异烟肼、利福平及吡嗪酰胺联合治疗至少9个月，最初2个月可加用链霉素。
