In vitro models for prediction of antimicrobial activity: a pharmacokinetic and pharmacodynamic perspective

The endpoints associated with conventional susceptibility testing, e.g., the minimum inhibitory concentration or minimum bactericidal concentration (MIC or MBC), are discrete in nature. These endpoint measurements do not provide any information, regarding the pharmacodynamic changes exhibited by the bacteria in reaction to the antibiotic activity during the incubation period. Another limitation of these susceptibility tests is the maintenance of constant antibiotic concentrations; this condition contrasts sharply to the continuously changing concentrations observed in vivo. To tackle these problems, various in vitro pharmacokinetic/pharmacodynamic models have been developed. Taking into consideration various pharmacokinetic determinants, such models allow more comprehensive study of the pharmacodynamic effects demonstrated by antibiotics. In this paper, the implications and usefulness of these in vitro models to the characterization of antimicrobial activity are discussed. Limitations associated with their use are also addressed.