Antistaphylococcal activities of teicoplanin and vancomycin in vitro and in an experimental infection

Abstract

The efficacies of vancomycin and teicoplanin in an experimental Staphylococcus aureus infection in granulocytopenic mice were related to their activities in vitro and their pharmacokinetic profiles. In vitro teicoplanin had a higher intrinsic activity than vancomycin did; and it also had a more favorable pharmacokinetic profile, resulting in higher peak concentrations in plasma, a longer elimination half-life, and a larger area under the concentration-time curve than those of vancomycin. To predict the antibacterial efficacies of the drugs in vivo on the basis of their activities in vitro and pharmacokinetics, a mathematical model was applied. In the model the in vitro effect was expressed as the difference in growth rate between control cultures and those in the presence of the antibiotic (ER), and the in vivo effect was expressed as the difference between numbers of CFU in control and antibiotic-treated animals (EN). The integral of ER against time, ERt, was calculated by using the concentrations found in vivo. A significant linear relationship was found between EN and ERt for different dosages at the same times (4 h) after drug administration as well as for the same doses at consecutive times, although at the lowest doses of teicoplanin the observed effect was less than the predicted effect.