Owens Robert C, Shorr Andrew F
Department of Pharmacy, and Clinical Pharmacy Specialist, Infectious Diseases, Division of Infectious Diseases, Maine Medical Center, Portland, ME 04102-3175, USA.
Am J Health Syst Pharm. 2009 Jun 15;66(12 Suppl 4):S23-30. doi: 10.2146/090087d.
Using the principles of pharmacokinetic (PK) and pharmacodynamic (PD) dosing, the optimal dosing strategies of beta-lactams, macrolides, fluoroquinolones, and aminoglycosides for the treatment of community-acquired pneumonia (CAP) are reviewed.
The optimal dosing of antimicrobials according to PK and PD principles is one method to reduce the misuse and overuse of the agents and antimicrobial resistance. Based on PK/PD profiles, antimicrobial agents are divided into three groups: agents with concentration-dependent killing (e.g., fluoroquinolones, aminoglycosides), agents with time- dependent killing and minimal or no persistent effects (e.g., beta-lactams in most circumstances), and agents with time-dependent killing and moderate-to-prolonged persistent effects (e.g., azithromycin).(19) With concentration-dependent agents such as fluoroquinolones, it is the total amount of drug administered that determines efficacy. With time-dependent agents such as macrolides and beta-lactams, it is the duration of exposure to a specific minimum inhibitory concentration (MIC). That part is straight forward. When a concentration-dependent killing drug is able to achieve its optimal peak:MIC, peak:MIC becomes the determinant of efficacy. When such a drug cannot achieve its optimal peak:MIC, AUC:MIC should be used to determine efficacy.
Optimizing the dose and duration of antimicrobial therapy via PK/PD principles is one strategy to reduce antimicrobial resistance. PK/PD-based dosing provides patient- and pathogen-specific therapy and have the potential to make antimicrobial therapy safer and more effective by accounting for factors such as renal function, underlying pathogen, and local patterns of resistance.
运用药代动力学（PK）和药效动力学（PD）给药原则，综述β-内酰胺类、大环内酯类、氟喹诺酮类和氨基糖苷类药物治疗社区获得性肺炎（CAP）的最佳给药策略。
根据PK和PD原则优化抗菌药物剂量是减少药物滥用和过度使用以及抗菌药物耐药性的一种方法。根据PK/PD特征，抗菌药物分为三组：浓度依赖性杀菌药物（如氟喹诺酮类、氨基糖苷类）、时间依赖性杀菌且最小或无持续效应的药物（如大多数情况下的β-内酰胺类）以及时间依赖性杀菌且有中度至延长持续效应的药物（如阿奇霉素）。（19）对于氟喹诺酮类等浓度依赖性药物，给药总量决定疗效。对于大环内酯类和β-内酰胺类等同时间依赖性药物，暴露于特定最低抑菌浓度（MIC）的持续时间决定疗效。这部分很简单。当浓度依赖性杀菌药物能够达到其最佳峰浓度：MIC时，峰浓度：MIC成为疗效的决定因素。当此类药物无法达到其最佳峰浓度：MIC时，曲线下面积：MIC应用于确定疗效。
通过PK/PD原则优化抗菌治疗的剂量和持续时间是减少抗菌药物耐药性的一种策略。基于PK/PD的给药提供针对患者和病原体的特异性治疗，并且通过考虑肾功能、潜在病原体和局部耐药模式等因素，有可能使抗菌治疗更安全、更有效。
