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 Emax-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 EC50 for the various dosing regimens averaged 5.2 micrograms/mL and was independent of dose. These parameters were used the simulate the bacterial 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.
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 Emax-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 EC50 for the various dosing regimens averaged 5.2 micrograms/mL and was independent of dose. These parameters were used the simulate the bacterial 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.
Authors: M Brunner; U Hollenstein; S Delacher; D Jäger; R Schmid; E Lackner; A Georgopoulos; H G Eichler; M Müller Journal: Antimicrob Agents Chemother Date: 1999-05 Impact factor: 5.191
Authors: Roland R Regoes; Camilla Wiuff; Renata M Zappala; Kim N Garner; Fernando Baquero; Bruce R Levin Journal: Antimicrob Agents Chemother Date: 2004-10 Impact factor: 5.191