Changes of Rifampicin Concentration in Cerebrospinal Fluid of Patients with Tuberculous Meningoencephalitis
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摘要:
目的 探讨鞘内注射利福平治疗结核性脑膜炎时脑脊液中利福平的浓度变化与疗效。 方法 收集确诊结核性脑膜炎患者40例，按入组标准随机分为2组，每组20例；2组均给予HRZE方案；A1组为非鞘内注射对照组、A2组鞘内注射利福平40 mg+地塞米松2.5 mg，1次/d；分别于0 h、4 h、8 h时间位点监测血液、脑脊液中利福平药物浓度（分别以bCxh和cCxh表示）。 结果 第0 h A2组脑脊液中利福平检测值明显高于A1组，P < 0.01；A2组有效率高于A1组；利福平血药浓度第4 h达到峰浓度，第8 h脑脊液利福平浓度处于较高水平，（cC 8 h）为3.34（1.03，51.60）µg/ mL，Nemenyi两两比较结果显示：cC0 h、cC4 h、cC8 h（P < 0.01）脑脊液药物浓度，差异有统计学意义（ P < 0.05）。 结论 鞘内注射利福平有助于提高脑脊液中的利福平的药物浓度，且疗效更显著。鞘内注射利福平使利福平药物浓度在第8 h仍处于较高水平。 Abstract:Objective To investigate the concentration and efficacy of rifampicin （RIF） in cerebrospinal fluid during intrathecal injection of RIF in the treatment of tuberculous meningitis. Methods Forty patients with tuberculous meningitis were randomly divided into two groups according to the admission criteria, and both groups were given HRZE regimen, A1 group was non-intrathecal injection control group, A2 group was given intrathecal injection of rifampicin 40 mg + dexamethasone 2.5 mg once a day, and the concentration of RIF in blood and cerebrospinal fluid （expressed by bCxh and cCxh） was monitored at 0 h, 4 h and 8 h, respectively. Results At the 0th hour, the value of RIF in cerebrospinal fluid in A2 group was significantly higher than that in A1 group, P < 0.01. The concentration of rifampicin in serum reached the peak at 4 h, and the concentration of rifampicin in cerebrospinal fluid was higher at 8 h （cC 8 h）, 3.34 （1.03, 51.60） µg/mL, The results showed that there were significant differences in cC0 h, cC4 h and cC8 h （P < 0.01）. Conclusions Intrathecal injection of RIF helps to increase the concentration of RIF in cerebrospinal fluid, and the curative effect is more significant. Intrathecal injection of Rifampin can keep the concentration of Rifampin at a high level at the 8th hour. -
表 1 2010年结核性脑膜炎临床评分标准[8]
Table 1. 2010 clinical scoring criteria for tuberculous meningitis
临床症状标准 最高得分6 症状持续至少 5 d 4 全身性的结核症状（≥1个）：体重减轻（儿童体重增加不足）、盗汗、持续咳嗽 > 2周 2 既往有与肺结核、TST 或 γ干扰素释放实验阳性（ < 10 岁儿童）患者密切接触史 2 颅神经麻痹症状 1 神经功能缺损症状（除外颅神经麻痹） 1 意识改变 1 脑脊液标准 最高得分4 外观清亮 1 细胞数：10～500/µL 1 淋巴细胞为主（ > 50%） 1 蛋白浓度大于 1 g/L 1 CSF糖/血糖 < 50% 或 CSF糖浓度绝对值 < 2.2 mmol/L 1 头颅影像标准 最高得分6 脑积水 1 基底池脑膜强化 2 结核瘤 2 脑梗死 1 强化扫描前脑基池处高信号 2 脑外结核证据 最高得分4 胸部平片提示活动性结核：两处结核灶 = 2；多处结核灶 = 4 2/4 CT / MRI / 超声 提示中枢神经系统以外结核 2 上皮细胞、痰、淋巴结、胃灌洗液、尿液、血培养抗酸染色或结核培养阳性 4 神经组织用核酸放大测定方法检测结核阳性 4 
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表 2 第0小时鞘内注射组与非鞘内注射组脑脊液中RIF检测值[M（P25，P75）]
Table 2. CSF RIF detaction value at 0 h in intrathecal injection group and non intrathecal injection group [M（P25，P75）]
组别 n RIFC0h Z P 非鞘内注射组（A1）（µg/ mL） 20 0.33（0.17，1.48） 鞘内注射组（A2）（µg/ mL） 20 1.42（0.67，2.15） −2.8 < 0.01* *P < 0.05。
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表 3 鞘内注射组与非鞘内注射组的患者临床疗效比较[n（%）]
Table 3. Comparison of clinical curative effect between intrathecal injection group and nonintrathecal injection group [n（%）]
组别 n 治疗有效 χ2 P 非鞘内注射组（A1） 20 12（60） 鞘内注射组（A2） 20 19（95） 31 < 0.01* *P < 0.05。
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表 4 鞘内注射利福平治疗结核性脑膜炎时各时间位点血清及脑脊液中利福平浓度[M（P25，P75）]
Table 4. Concentration of RFP in serum and CSF at different time points during intrathecal RIF injection in the treatment of tuberculous meningitis [M（P25，P75）]
RIF药物浓度 C0h C4h C8h F P 血药浓度bCxh（µg/ mL） 5.34（3.05，7.68） 9.38（5.28，11.75） 3.93（2.91，6.84） 17.50 < 0.01* 脑脊液药物浓度cCxh（µg/ mL） 1.42（0.69，2.15） 2.07（1.25，213.94） 3.34（1.03，51.60） 11.17 < 0.01* *P < 0.05。
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