PHARMACOKINETIC AND PHARMACODYNAMIC MODELS OF THE ANTISTAPHYLOCOCCAL EFFECTS OF MEROPENEM AND CLOXACILLIN IN-VITRO AND IN EXPERIMENTAL-INFECTION

The efficacies of meropenem (MPM) and cloxacillin (CLC) against two St aphylococcus aureus strains were established in vitro. A pharmacodynam ic model equation, based on the concept that the killing rate depends on concentration and time, was fitted to the numbers of CFU, The param eters of the equation are maximum killing rate, time point of maximum killing, and 50% effective concentration (EC50), The EC(50)s for the t wo strains were 0.047 and 0.040 mg/liter, respectively, for MPM and 0. 105 and 0.121 mg/liter, respectively, for CLC, Calculated values of th e parameters were used to predict the numbers of CFU at exponentially decreasing concentrations in vitro as well as in an experimental infec tion model, The prediction for in vitro conditions gave a satisfactory fit (R-2, between 0.862 and 0.894). In vivo the numbers were predicte d with the assumption that killing rate in vivo is proportional to tha t in vitro (R-2, between 0.731 and 0.973), The proportionality factor ranged between 0.23 and 0.42; this variation was due mainly to covaria tion with growth rates in control animals, without other significant d ifferences between antibiotics or strains.