Antimicrobial Fundamental Concepts（抗菌基本概念）.pdf

Antimicrobial Fundamental Concepts Pharmacodynamics and Therapeutic Drug Monitoring Pharmacokinetics versus pharmacodynamics Pharmacokinetics mathematically describe the relationship of antibiotic concentration to time. Terminology that is typically associated with pharmacokinetics includes: absorption, distribution, metabolism, elimination, half-life, volume of distribution, and area under the concentration-time curve (AUC). Pharmacodynamics describe the relationship of antibiotic concentration to pharmacologic effect or microorganism death. The three main pharmacodynamic parameters that are used are the peak to minimal inhibitory concentration ratio (peak/MIC), the AUC to MIC ratio (AUC/MIC), and the time the drug concentration remains above the MIC (T>MIC). Concentration independent versus concentration dependent Concentration independent (time dependent) means that the rate and extent of microorganism killing remain unchanged regardless of antimicrobial concentration. The pharmacodynamic parameter that is most often predictive of outcome for concentration independent drugs is T>MIC, although the AUC/MIC can be used because the AUC takes both the antimicrobial concentration and time into account. Examples of concentration independent antimicrobials include: beta-lactams, vancomycin, macrolides, aztreonam, carbapenems, clindamycin, tetracyclines, quinupristin/dalfopristin, flucytosine, and azole antifungals. Concentration dependent (time independent) means that the rate and extent of microorganism killing are a function of the antimicrobial concentration (increase as the concentration increases). The pharmacodynamic parameter that is most often predictive of outcome for concentration dependent drugs is peak/MIC, although the AUC/MIC can be used because the AUC takes both the antimicrobial concentration and time into account. Examples of concentration dependent antimicrobials include: fluoroquinolones, aminoglycosides, and amphotericin B.