Pharmacokinetic pharmacodynamic modeling of the antibiotic effect of piperacillin in vitro

Purpose. It was the aim of the present study to investigate the in vitro antimicrobial effects of the beta-lactam antibiotic piperacillin on Escherichia coli using concentration-time profiles similar to those encountered in vivo. Methods. An in vitro dilution model was used to expose E. coli to various piperacillin concentration profiles. The antimicrobial effect was evaluated by determination of the number of bacteria over time. Results. A modified E(max)-model was found appropriate to describe the pharmacodynamic effect. This model was linked with the respective piperacillin concentrations to provide a suitable pharmacokinetic-pharmacodynamic (PK-PD) model. The average growth half-life in absence of piperacillin was 28 min and the maximum kill half-life was 25 min. The EC(50) for the various dosing regimens averaged 5.2 mu g/mL and was independent of dose. These parameters were used the simulate the bactericidal effects of commonly administered doses or dosing regimens in humans. Conclusions. Based on the in vitro data a more frequent administration of piperacillin will be more efficacious. The proposed PK-PD-model allows a more detailed evaluation of dosing regimens than the use of minimum inhibitory concentrations.