Li R C, Nix D E, Schentag J J
Department of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin.
J Pharm Sci. 1994 Jul;83(7):970-5. doi: 10.1002/jps.2600830711.
A simple pharmacodynamic model has been developed to describe the bacterial kinetics exhibited by beta-lactam antibiotics. In contrast with previous models that only characterized the early killing phase of a time-kill curve, the present model is capable of simultaneously describing both the killing and regrowth phases. The model relied on the use of both first-order bactericidal and resistance formation rate constants to accurately define the time-dependent changes in the bacterial populations of an antibiotic-treated culture. The concentration dependency of the bactericidal rate constant was further delineated using a saturable-receptor model. Furthermore, an exponential decrease in the resistance formation rate with increasing antibiotic concentrations was demonstrated. The evolving pharmacodynamic model was also explored via computer simulations by perturbing the two governing rate constants. The model was subsequently applied to the description of time-kill data for amoxicillin, penicillin G, and cephalexin against Escherichia coli. The description of amdinocillin's action against E. coli was not as comprehensive because of the existence of a second killing phase. However, this model can be applicable to many classes of antibiotics that display the usual killing and regrowth phases in time-kill studies. The pharmacodynamic model can potentially improve the prediction of bacterial killing and regrowth and foster an improved understanding of complex antimicrobial pharmacodynamics.
已开发出一种简单的药效学模型来描述β-内酰胺类抗生素呈现的细菌动力学。与之前仅表征时间-杀菌曲线早期杀菌阶段的模型不同，当前模型能够同时描述杀菌和再生长阶段。该模型依靠使用一级杀菌和耐药性形成速率常数来准确界定抗生素处理培养物中细菌群体随时间的变化。使用饱和受体模型进一步描绘了杀菌速率常数的浓度依赖性。此外，还证明了随着抗生素浓度增加，耐药性形成速率呈指数下降。通过扰动两个控制速率常数，还通过计算机模拟探索了不断演变的药效学模型。随后将该模型应用于描述阿莫西林、青霉素G和头孢氨苄对大肠杆菌的时间-杀菌数据。由于存在第二个杀菌阶段，氨比西林对大肠杆菌作用的描述不够全面。然而，该模型可适用于在时间-杀菌研究中呈现通常杀菌和再生长阶段的许多类抗生素。该药效学模型有可能改善对细菌杀灭和再生长的预测，并促进对复杂抗菌药效学的更好理解。
