Possible approaches to the simulation of antibiotic kinetics and the determination of antibacterial activity in vitro.

Various methods of determining antibacterial effects in vitro by simulation of antibiotic kinetics were investigated. MICs were determined in fluids with and without proteins. Only concentrations of free drug were antibacterially active, and these concentrations should therefore be simulated in culture media without protein. Varying drug concentrations can easily be simulated in our in-vitro system, but the question remains which of the concentrations found in the different body fluids is the most representative. Cephalosporins were more active when phagocytosis was simulated, as shown by the continuous elimination of approximately 90% of the bacteria. If phagocytosis was not simulated, the effects of long-lasting concentrations were not decreased as much as those of concentrations corresponding to short half-lives and repeated doses.