Bacterial elimination and therapeutic effectiveness under different schedules of amoxicillin administration

Bacterial elimination kinetics under different simulated administration schedules of amoxicillin was followed in vitro by using a simple model for simulation of pharmacokinetic parameters. The results were compared to those obtained in lethally infected mice by determining the viable bacterial count in the blood at various times post-infection and under different schedules of amoxicillin administration. A satisfactory correlation could be established between the in vitro and in vivo results. Multiple administration of amoxicillin was found to induce a beta-lactamase in vitro as well as in vivo in the Escherichia coli strain used. No difference was however found between the various administration schedules of amoxicillin in terms of surviving animals. Taking into account the lasting elimination of viable bacteria from the blood, the best treatment of E. coli-infected mice was found to be a twice daily administration of the higher amoxicillin dose.