Burgess D S
University of Texas at Austin, USA.
Chest. 1999 Mar;115(3 Suppl):19S-23S. doi: 10.1378/chest.115.suppl_1.19s.
Pharmacodynamic properties can be used to divide antibiotics into two major classes based on their mechanism of bactericidal action: (1) concentration-dependent drugs, such as aminoglycosides and fluoroquinolones, and (2) concentration-independent drugs, including the beta-lactams. Antibiotics also differ in the postantibiotic effect (PAE) that they exert. In general, concentration-dependent drugs have a more prolonged PAE than concentration-independent drugs, particularly against Gram-negative pathogens. Pharmacodynamic classifications have important implications for the planning of drug regimens. For concentration-dependent drugs, peak concentration to minimal inhibitory concentration (MIC) ratios of approximately 10 are associated with clinical success. Therefore, high drug levels should be the goal of therapy. This is best achieved by high doses taken once daily. This approach, however, is not feasible for the fluoroquinolones owing to dose-limiting CNS toxicity. Concentration-independent agents are most effective when the duration of serum concentrations is higher than the pathogen's MIC (time >MIC) for a significant proportion of the dosing interval. Frequent dosing or continuous infusions can increase the time >MIC. Concentrations of antibiotics that are sublethal can permit the emergence of resistant pathogens. Optimization of antibiotic regimens on the basis of pharmacodynamic principles could thus significantly diminish the emergence of antibiotic resistance.
根据杀菌作用机制，药效学特性可将抗生素分为两大类：（1）浓度依赖性药物，如氨基糖苷类和氟喹诺酮类；（2）浓度非依赖性药物，包括β-内酰胺类。抗生素发挥的抗生素后效应（PAE）也有所不同。一般来说，浓度依赖性药物的PAE比浓度非依赖性药物更长，尤其是对革兰氏阴性病原体。药效学分类对给药方案的制定具有重要意义。对于浓度依赖性药物，峰值浓度与最低抑菌浓度（MIC）之比约为10与临床成功相关。因此，高药物水平应是治疗的目标。这最好通过每日一次服用高剂量来实现。然而，由于剂量限制性中枢神经系统毒性，这种方法对氟喹诺酮类药物不可行。当血清浓度持续时间在给药间隔的很大一部分时间内高于病原体的MIC（时间＞MIC）时，浓度非依赖性药物最为有效。频繁给药或持续输注可增加时间＞MIC。亚致死浓度的抗生素会使耐药病原体出现。因此，根据药效学原理优化抗生素方案可显著减少抗生素耐药性的出现。
