Roosendaal R, Bakker-Woudenberg I A
Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.
Scand J Infect Dis Suppl. 1990;74:155-62.
In agreement with results obtained in the thigh infection model for which there is no human equivalent, the impact of the dosage schedule on efficacy in various clinically relevant experimental lung infections is related to the class of antibiotic. The efficacy of beta-lactams increases with increasing frequency of administration. Sustained antibiotic concentrations in serum at a relatively low level are more effective than high peak concentrations at intervals. In contrast, the dosing interval has little impact on the activity of aminoglycosides, which is mainly dependent on the total amount of antibiotic in serum during treatment, either as short lasting high peaks or as long lasting relatively low concentrations. Limited data available on quinolones suggest a slight increase in efficacy with increasing dosing intervals. These differences in efficacy correlate with differences in the pharmacodynamics of antibiotics of different classes as seen in vitro as well as in the lungs of infected animals. Knowledge about both the pharmacokinetics and pharmacodynamics of antibiotics is required for the correct interpretation of comparative studies on antibiotic efficacy in experimental infections, and also for the evaluation of experimental data as support for the proper design of clinical trials.
与在无人体等效模型的大腿感染模型中获得的结果一致，给药方案对各种临床相关实验性肺部感染疗效的影响与抗生素类别有关。β-内酰胺类抗生素的疗效随给药频率增加而提高。血清中持续的较低水平抗生素浓度比间隔出现的高浓度峰值更有效。相比之下，给药间隔对氨基糖苷类抗生素的活性影响较小，其活性主要取决于治疗期间血清中抗生素的总量，无论是短暂的高浓度峰值还是持续的相对低浓度。关于喹诺酮类药物的现有数据有限，表明随着给药间隔增加疗效略有提高。这些疗效差异与不同类别抗生素在体外以及感染动物肺部的药效学差异相关。正确解释实验性感染中抗生素疗效的比较研究以及评估作为支持临床试验合理设计的实验数据，都需要了解抗生素的药代动力学和药效学。
