Optimisation des traitements antibacteriens sur base de proprietes pharmacodynamiques des antibiotiques

Antibiotics of different classes are characterized by markedly distinct pharmacodynamic properties which are important to consider for their optimal use. This paper reviews the experimental and clinical data which have led to their discovery. β-lactams, glycopeptides, macrolides and tetracyclines are largely dose-independent and time-dependent antibiotics for which the time above the MIC is the main predictor of efficacy. These antibiotics should therefore be administered frequently, and there is no direct advantage in creating high peak levels per se. To the contrary, fluoroquinolones and aminoglycosides are antibiotics which are primarily concentration-dependent. For fluoroquinolones, the best predictor of efficacy is the ratio between the area under the curve of the serum concentration versus time and the MIC of the offending organism, whereas for aminoglycosides a large ratio between the serum peak concentration, and the MIC affords optimal activity. Thus fluoroquinolones gain in being dosed at sufficiently large daily doses but frequently that dose can be splitted in several administrations. Conversely, aminoglycosides will be very more effective and less toxic when administered intermittently, which led to design to once-a-day administration scheme. Optimization of antibiotic treatments is likely to be an important determinant for an improved, more cost-effective management of the infective pathology as well as for the prevention of bacterial resistance.