Moffie B G, Hoogeterp J J, Lim T, Douwes-Idema A E, Mattie H
University Hospital, Department of Infectious Diseases, Leiden, The Netherlands.
J Antimicrob Chemother. 1993 Mar;31(3):403-11. doi: 10.1093/jac/31.3.403.
The activity of netilmicin and tobramycin against Pseudomonas aeruginosa was assessed in vitro in the presence of constant and exponentially declining concentrations, and in mice in an experimental thigh infection. The activity in vitro at constant concentrations was expressed as the maximal killing rate (ER) during 3 h of exposure. On the basis of the quantitative relation between E(R) and the drug concentration, the numbers of cfu expected at consecutive times, at constant as well as at declining concentrations, were predicted. The relationship between observed numbers and predicted values of ERt were similar under both conditions for both drugs. On the same basis the numbers of cfu expected in the experimental thigh infection were predicted. There was indeed a significant linear relationship between observed numbers of cfu in homogenized muscle and the values predicted on the basis of the pharmacokinetics of the aminoglycosides, but the slope of this relationship was only 0.22. There was no difference in this respect between the two antibiotics. It is concluded that the efficacy of netilmicin and tobramycin against P. aeruginosa is considerably less in vivo than in vitro, but the relation is about the same for the two drugs; therefore the slightly higher activity of tobramycin in vitro is relevant in the in-vivo situation.
在存在恒定浓度和指数下降浓度的情况下，对奈替米星和妥布霉素针对铜绿假单胞菌的活性进行了体外评估，并在小鼠实验性大腿感染中进行了评估。恒定浓度下的体外活性表示为暴露3小时期间的最大杀灭率（ER）。根据E(R)与药物浓度之间的定量关系，预测了在恒定浓度和下降浓度下连续时间预期的cfu数量。两种药物在两种条件下观察到的数量与ERt预测值之间的关系相似。基于同样的基础，预测了实验性大腿感染中预期的cfu数量。在匀浆肌肉中观察到的cfu数量与基于氨基糖苷类药物药代动力学预测的值之间确实存在显著的线性关系，但这种关系的斜率仅为0.22。两种抗生素在这方面没有差异。结论是，奈替米星和妥布霉素对铜绿假单胞菌的体内疗效远低于体外，但两种药物的关系大致相同；因此，妥布霉素在体外稍高的活性在体内情况下是相关的。
