ISSN:
1573-904X
Keywords:
piperacillin
;
Escherichia coli
;
Emax-model
;
PK-PD modeling
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. It was the aim of the present study to investigate the in vitro antimicrobial effects of the β-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 pharmaco-kinetic-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 µg/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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1016085402278
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