Nau R, Prange H W, Kinzig M, Frank A, Dressel A, Scholz P, Kolenda H, Sörgel F
Department of Neurology, University of Göttingen, Germany.
Antimicrob Agents Chemother. 1996 Mar;40(3):763-6. doi: 10.1128/AAC.40.3.763.
Ceftazidime has proven to be effective for the treatment of bacterial meningitis caused by multiresistant gram-negative bacteria. Since nosocomial central nervous system infections are often accompanied by only a minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive hydrocephalus who had undergone external ventriculostomy were studied (n = 8). Serum and CSF were drawn repeatedly after the administration of the first dose of ceftazidime (3 g over 30 min intravenously), and concentrations were determined by high-performance liquid chromatography by using UV detection. The concentrations of ceftazidime in CSF were maximal at 1 to 13 h (median, 5.5 h) after the end of the infusion and ranged from 0.73 to 2.80 mg/liter (median, 1.56 mg/liter). The elimination half-lives were 3.13 to 18.1 h (median, 10.7 h) in CSF compared with 2.02 to 5.24 h (median, 3.74 h) in serum. The ratios of the areas under the concentration-time curves in CSF and serum (AUCCSF/AUCS) ranged from 0.027 to 0.123 (median, 0.054). After the administration of a single dose of 3 g, the maximum concentrations of ceftazidime in CSF were approximately four times higher than those after the administration of 2-g intravenous doses of cefotaxime (median, 0.44 mg/liter) and ceftriaxone (median, 0.43 mg/liter) (R. Nau, H. W. Prange, P. Muth, G. Mahr, S. Menck, H. Kolenda, and F. Sörgel, Antimicrob. Agents Chemother. 37:1518-1524, 1993). The median AUCCSF/AUCS ratio of ceftazidime was slightly below that of cefotaxime (0.12), but it was 1 order of magnitude above the median AUCCSF/AUCS of ceftriaxone (0.007) (Nau et al., Antimicrob. Agents Chemother. 37:1518-1524, 1993). The concentrations of ceftazidime observed in CSF were above the MICs for most Pseudomonas aeruginosa strains. However, they are probably not high enough to be rapidly bactericidal. For this reason, the daily dose should be increased to 12 g in cases of P. aeruginosa infections of the central nervous system when the blood-CSF barrier is minimally impaired.
头孢他啶已被证明对治疗由多重耐药革兰氏阴性菌引起的细菌性脑膜炎有效。由于医院获得性中枢神经系统感染通常仅伴有轻微的血脑脊液（CSF）屏障功能障碍，因此对接受了外部脑室造瘘术的非炎性闭塞性脑积水患者进行了研究（n = 8）。在静脉内给予第一剂头孢他啶（30分钟内静脉注射3g）后反复采集血清和脑脊液，并使用紫外检测通过高效液相色谱法测定浓度。头孢他啶在脑脊液中的浓度在输注结束后1至13小时（中位数为5.5小时）达到最大值，范围为0.73至2.80mg /升（中位数为1.56mg /升）。脑脊液中的消除半衰期为3.13至18.1小时（中位数为10.7小时），而血清中的消除半衰期为2.02至5.24小时（中位数为3.74小时）。脑脊液和血清中浓度 - 时间曲线下面积的比值（AUCCSF / AUCS）范围为0.027至0.123（中位数为0.054）。给予3g单剂量后，脑脊液中头孢他啶的最大浓度比静脉注射2g剂量的头孢噻肟（中位数为0.44mg /升）和头孢曲松（中位数为0.43mg /升）后的最大浓度高约四倍（R. Nau，H. W. Prange，P. Muth，G. Mahr，S. Menck，H. Kolenda和F. Sörgel，Antimicrob. Agents Chemother. 37：1518 - 1524，1993）。头孢他啶的中位数AUCCSF / AUCS比值略低于头孢噻肟（0.12），但比头孢曲松的中位数AUCCSF / AUCS（0.007）高1个数量级（Nau等人，Antimicrob. Agents Chemother. 37：1518 - 1524，1993）。在脑脊液中观察到的头孢他啶浓度高于大多数铜绿假单胞菌菌株的最低抑菌浓度。然而，它们可能不够高，不足以迅速杀菌。因此，当血脑脊液屏障受损最小时，中枢神经系统铜绿假单胞菌感染病例的每日剂量应增加至12g。
