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儿童急性细菌性脑膜炎短疗程每日单次头孢曲松单药治疗:一项瑞士多中心研究的结果。第二部分:细菌学结果。

Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter study. Part II: Bacteriological results.

作者信息

Hohl P, Martin E, Kayser F H

机构信息

Department of Pharmaceutical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.

出版信息

Infection. 1990 Mar-Apr;18(2):78-82. doi: 10.1007/BF01641419.

Abstract

The in vitro activity of ceftriaxone, ampicillin and chloramphenicol was studied at a reference laboratory against the isolates of the first 33 patients enrolled in a pediatric Swiss Multicenter Meningitis Study. The predictive value of the MIC data of 31 of the strains was further corroborated by two sets of bacterial killing curves in broth supplemented with 2 g/l of albumin. Ceftriaxone had the lowest geometric mean MIC values against all groups of isolates except for ampicillin against Streptococcus agalactiae. The bactericidal activity of ceftriaxone and that of ampicillin, alone and in combination with chloramphenicol, was compared at six times the respective MICs and at pharmacologically readily achievable concentrations in cerebrospinal fluid. The bactericidal power of ceftriaxone at six times the MIC was as good or better than that of ampicillin alone or in combination against Neisseria meningitidis and Streptococcus pneumoniae despite the very low drug concentrations of ceftriaxone compared to that of the competitors; and it was barely lower at six times the MIC and at 1 mg/l (a level that is readily surpassed in CSF at the 24 h trough level after a single daily dose of ceftriaxone of 100 mg/kg (neonates 50 mg/kg) than that of ampicillin and chloramphenicol at much higher concentrations against Haemophilus influenzae type b.

摘要

在一家参考实验室对头孢曲松、氨苄西林和氯霉素针对瑞士多中心小儿脑膜炎研究中招募的前33例患者的分离菌株进行了体外活性研究。通过在添加2 g/l白蛋白的肉汤中的两组细菌杀灭曲线,进一步证实了31株菌株的MIC数据的预测价值。除了氨苄西林对无乳链球菌外,头孢曲松对所有分离菌株组的几何平均MIC值最低。在脑脊液中分别为各自MIC的6倍以及药理学上易于达到的浓度下,比较了头孢曲松以及氨苄西林单独和与氯霉素联合使用时的杀菌活性。尽管与竞争药物相比头孢曲松的药物浓度非常低,但在6倍MIC时,头孢曲松对脑膜炎奈瑟菌和肺炎链球菌的杀菌能力与氨苄西林单独使用或联合使用时一样好或更好;在6倍MIC以及1 mg/l(在每日单次剂量100 mg/kg(新生儿50 mg/kg)头孢曲松后24小时谷浓度时脑脊液中很容易超过该水平)时,其杀菌能力仅略低于氨苄西林和氯霉素在高得多的浓度下对b型流感嗜血杆菌的杀菌能力。

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