Optimal antibiotic dosing. The pharmacokinetic-pharmacodynamic interface.

Successful pharmacotherapy for respiratory tract (and other) infections should integrate both the pharmacokinetic (PK) and the pharmacodynamic (PD) properties of antimicrobial agents. Antibiotics can be classified according to their pattern of antimicrobial activity: concentration-dependent killing, time-dependent killing, or a hybrid pattern. With the concentration-dependent killing pattern, the higher the drug concentration relative to pathogen minimum inhibitory concentration (MIC), the greater the rate and extent of antimicrobial activity. The time-dependent killing pattern is dependent on the duration of pathogen exposure to an antibiotic. The hybrid pattern of antimicrobial activity involves both the duration of pathogen exposure to the antibiotic and a prolonged, persistent post-antibiotic effect. The aminoglycosides and fluoroquinolones exhibit concentration-dependent killing. Thus, the main PK-PD parameters that correlate with their efficacy are the ratio of peak serum drug concentration to MIC and the ratio of the area under the concentration versus time curve to MIC. The percentage of time during the dosing interval that serum drug concentrations exceed the MIC is the only PK-PD parameter that correlates with beta-lactam efficacy. Knowledge of these PK-PD parameters is of value in optimizing the dosing regimens for all antimicrobial agents.