Rational dosing of antimicrobial agents: pharmacokinetic and pharmacodynamic strategies.

PURPOSE: 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.
SUMMARY: 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.
CONCLUSION: 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.