Critères pharmacocinétiques du choix d'un antibiotique pour l'antibioprophylaxie en chirurgie

Abstract

The prevention of surgical infections with perioperative prophylactic antibiotics is experimentally and clinically well founded in both principle and practice. The evaluation of the role of antimicrobial agents in the success or failure of infection prophylaxis in surgery involves a discussion of both the pharmacokinetic and the pharmacodynamic properties of particular agents. A main concern in surgical prophylaxis is the relation between the respective time course of antibiotic concentrations in serum and in the tissue (wound). Several problems arise in both the measurement and the interpretation of drug concentrations in tissues and the results of this approach are still controversial. However, the knowledge of the numerous factors influencing the penetration into a tissue and the characteristics of the relative distribution of the antibiotic between the compartments inside the tissue, i.e. the vascular, interstitial and intracellular spaces, could allow a valuable approach to this problem. The concentrations of free drugs in serum are valuable predictors of the time course of unbound drug in interstitial fluid, where the bacteria are generally located. An increase in protein binding does not reduce the area under the curve (AUC) of free drug for β lactam agents eliminated predominantly by glomerular filtration, but prolonges their climination half life. Timing and route of administration are also important factors to consider in relation with the parmacokinetic profile of the drug. Pharmacodynamic studies of persistent growth suppression and bactericidal activity predict that the period during which the free drug concentration exceeds the MIC is an important parameter of the efficacy of β lactam antibiotics. In the opposite, the Cmax and/or the AUC are the major parameters of the efficacy of aminoglycosides and quinolones against Gram negative bacteria. Thus, the goal of prophylaxis with β lactams could be to provide levels of free drug above the MIC for the whole surgical period, while the obtention of a high Cmax with a one-day therapy should be required for aminoglycosides. Further clinical trials are warranted to assess this approach.