Decazes J M, Ernst J D, Sande M A
Antimicrob Agents Chemother. 1983 Oct;24(4):463-7. doi: 10.1128/AAC.24.4.463.
Ceftriaxone was highly active in eliminating Escherichia coli from the cerebrospinal fluid of rabbits infected with experimental meningitis. However, concentrations equal to or greater than 10 times the minimal bactericidal concentration had to be achieved to ensure optimal efficacy (rate of kill, 1.5 log10 CFU/ml per h). In contrast to other beta-lactams studied in this model, ceftriaxone concentrations in cerebrospinal fluid progressively increased, whereas serum steady state was obtained by constant infusion. The percent penetration was 2.1% after 1 h of therapy, in contrast to 8.9% after 7 h (P less than 0.001). In vitro time-kill curves done in cerebrospinal fluid or broth more closely predicted the drug concentrations required for a maximum cidal effect in vivo than that predicted by determinations of minimal inhibitory or bactericidal concentrations.
头孢曲松在清除感染实验性脑膜炎的兔脑脊液中的大肠杆菌方面具有高度活性。然而，必须达到等于或大于最低杀菌浓度10倍的浓度才能确保最佳疗效（杀菌速率，每小时1.5 log10 CFU/ml）。与该模型中研究的其他β-内酰胺类药物不同，脑脊液中的头孢曲松浓度逐渐升高，而通过持续输注可获得血清稳态。治疗1小时后的穿透率为2.1%，而7小时后为8.9%（P小于0.001）。在脑脊液或肉汤中进行的体外时间-杀菌曲线比通过测定最低抑菌或杀菌浓度所预测的更能准确预测体内最大杀菌效果所需的药物浓度。
