COLISTIN BACTERICIDAL EFFECT ON ESCHERICH IA-COLI - MODEL AND SIMULATION OF PHARMACOKINETIC PHARMACODYNAMIC RELATIONSHIPS TO PREDICT EFFICACY IN VETERINARY ANTIBIOTHERAPY/

Pharmacodynamics studies consider three main parameters: the size of t he bacterial population, the concentration of the antibiotic and the d uration of its action. The pharmacodynamic characteristics ofcolistin were stud ied in vitro with Escherichia coli. The bacterial kinetics w ere fitted using differential equations. The mathematical model gave q ualitative and quantitative information about the characteristics of t he antibiotic-bacteria association. Above all, when linked to a pharma cokinetic model, the model permitted the prediction of the drug's effi ciency. Simulations of various dosage levels in which the administrati on route, dose sire, or interval between doses varied, permitted a mor e rational optimization than a prediction of efficacy based on the tim e taken to achieve antibiotic plasmatic concentrations above the minim al inhibitory concentration. Pharmacokinetic/pharmacodynamic modeling seems to be an interesting possibility for determining antibiotic dosi ng levels during the preclinical phase.