Pharmacokinetic-pharmacodynamic modeling of antibacterial activity of cephalexin on E. coli in presence of canine serum

SUMMARY The aim of this study was to evaluate the activity of cephalexin and the immune response factors present in canine serum on E. coli ATCC 25922, using a dynamic one step dilution in vitro one compartmental model, simulating cephalexin concentrations in this biological fluid during the elimination phase after its administration of a therapeutic dose to a dog. A mathematical model was used to fit the experimental data and to simulate expected kill-curves for different single doses of cephalexin. The minimum inhibitory concentration of cephalexin was not modified by presence of serum. The kill-rate and the time required for bacterial regrowth were increased by presence of canine serum. The time period in which the bacteria were exposed to subinhibitory concentrations of cephalexin after a dose was the determining factor for the persistence of antibiotic activity and this period was prolonged when canine serum was incorporated into the in vitro assay. Those findings probably reflect the in vivo situation more closely than other in vitro assays performed in standard culture medium in absence of the immune response of the host. Based on the results of the present study is feasible to modelize the time-kill data for changing cephalexin concentrations. This is a useful method to simulate and evaluate the efficacy of different doses of this antibiotic on E. coli.