[In vitro model for the study of the concentration kinetics of antibiotic combinations and their antibacterial...

The concentration kinetics of combinations of antibiotics similar to those taking place after i.v. administration was simulated in an in vitro model taking into account the different half-life periods of the antibiotics. A hose pump was used for continuous supply of sterile nutrient to a liquid bacterial culture containing both antibiotics in a preselected concentration and for removal of fluid from the system at an identical flow rate. To account for the different half-life periods of the antibiotics, a solution containing the antibiotic having a longer half-life in a corresponding concentration was continuously added by pumping. Samples were taken at fixed intervals to determine bacterial counts and check the expected concentrations of active substance did not contain antibiotics. This model has been developed to enable a determination of the dynamic relationship between the course of concentrations of antibiotics and their antibacterial activity. To permit a statement on the synergistic, indifferent or antagonistic activity of the combination, in analogy to the FIC indices in the checkerboard technique, the relative reduction of the bacterial count by the combination as compared to the individual components at time t was calculated. The model has been demonstrated by the example of the combined action of azlocillin and gentamicin against a strain of Klebsiella pneumoniae. In a simple way, the model permits any increase in the number of combination partners having different half-life periods. The mathematical development of the model is explained in detail.