The importance of appropriate antimicrobial dosing: Pharmacokinetic and pharmacodynamic considerations

The increasing antimicrobial resistance of common respiratory pathogens has led to a reevaluation of the selection of antimicrobial dosing regimens in terms of their pharmacokinetic (PK) and pharmacodynamic (PD) properties. Pharmacokinetics, when considered as part of a specific dosing regimen, can help determine the time course of drug concentrations in the serum, tissues, body fluids, and at the site of infection. Pharmacodynamics provides surrogate markers for clinical and bacteriologic efficacy based on the relationships between the serum and tissue concentrations of selected antimicrobial agents relative to the mean inhibitory concentrations of causative bacteria over time. Ultimately, the interrelationships between PK and PD parameters measured for standard dosing regimens determine the time course of the drug's concentration at the site of infection and the impact of the agent's bacteriologic and clinical efficacy. In this review, the distinctive patterns of antimicrobial activity based on PK/PD parameters are discussed. Various antibiotics and bacterial pathogens are used as models to demonstrate the utility of PK/PD parameters in predicting the in vivo efficacy of antimicrobial therapy. The use of computer modeling with Monte Carlo population simulations can further enhance the predictability of antimicrobial efficacy when using PK/PD parameters. This article also provides a reevaluation of bacterial susceptibility breakpoints defined by the National Committee for Clinical Laboratory Standards contrasted with the use of PK/PD parameters.