Signification clinique des corrélations pharmacocinétique/pharmacodynamie des antibiotiques chez les patients de réanimation

Patients hospitalized in intensive care units frequently require a treatment with antibiotics and exhibit specific problems in term of determination of the better dosage regimen to administer. Indeed, the physiopathologic conditions of these patients and the other treatments they receive are able to induce significant modifications of the pharmacokinetic profiles of several drugs and to increase the variability in their serum concentrations. Therefore, it is of interest to use all the approaches, which provide solutions to control the pharmacokinetic variability and to help in the determination of an adequate dosage. In the recent years, the research of surrogate makers able to predict the bacteriologic and clinical issue of an infection treatment has been a major tool in the pharmacology of antibiotics. These surrogate markers have been determined by defining the pharmacodynamics of the antibiotics, i.e. concentration or time-dependent bactericidal effect, the post antibiotic effect or the mutation prevention concentration and by combining them with their pharmacokinetics in order to calculate for each antibiotic/bacteria couple and each patient the optimal dosage regimen designed to obtain as soon as possible the better clinical outcome and also to minimize as much as possible the risk of resistant mutant strains selection. Inhibitory quotient, inhibitory area under the curve and time over minimum inhibitory concentration are the most important parameters able to modify the clinical issue of an infection in animal models and in humans and are increasingly used in clinical practice.