Rational dosing of antimicrobial agents: pharmacokinetic and pharmacodynamic strategies

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.