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

GIACOMINO, N.; CERRA, M.; GUMIY, D.; STIEFEL, S.; NOTARO, U.; BARONI, E.; FORMENTINI, E.

REVUE DE MEDECINE VETERINAIRE

ECOLE NATIONALE VETERINAIRE TOULOUSE

Lugar: Toulouse; Año: 2012

0035-1555

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, usinga dynamic one step dilution in vitro one compartmental model, simulatingcephalexin concentrations in this biological fluid during the elimination phaseafter its administration of a therapeutic dose to a dog. A mathematical modelwas used to fit the experimental data and to simulate expected kill-curves fordifferent single doses of cephalexin. The minimum inhibitory concentrationof cephalexin was not modified by presence of serum. The kill-rate and thetime required for bacterial regrowth were increased by presence of canineserum. The time period in which the bacteria were exposed to subinhibitoryconcentrations of cephalexin after a dose was the determining factor for thepersistence of antibiotic activity and this period was prolonged when canineserum was incorporated into the in vitroassay. Those findings probably reflectthein vivosituation more closely than other in vitroassays performed in standardculture medium in absence of the immune response of the host. Based on theresults of the present study is feasible to modelize the time-kill data for changingcephalexin concentrations. This is a useful method to simulate and evaluatethe efficacy of different doses of this antibiotic on E. coli.