Impact of pharmacodynamics on breakpoint selection for susceptibility testing

The main parameters used to indicate whether the use of an antimicrobial has a reasonable chance of success are the classifications "resistant" and "susceptible." The criteria used in the past to categorize. bacteria as susceptible or resistant were mainly based on frequency distributions and directed at discriminating susceptible from resistant subpopulations. During the last decade dose-effect relationships of antimicrobials have been established. The clinical breakpoint of an antimicrobial follows directly from the relationship between pharmacokinetic parameter value at doses commonly used to treat infections and the pharmacokinetic-pharmacodynamic index value necessary to achieve a maximum effect. In drug-development this has radically changed the approach to dose-finding studies and establishing tentative breakpoints. The increasing understanding in pharmacokinetic-pharmacodynamic relationships has a profound impact on the denotations. "susceptible" and "resistant" and thereby provides the clinician with better guidance of antimicrobial therapy.