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Antimicrobial Agents and Chemotherapy, July 1998, p. 1731-1737, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Comparisons between Antimicrobial Pharmacodynamic Indices and Bacterial Killing as Described by Using the Zhi Model

S. Corvaisier,1 P. H. Maire,1,2,* M. Y. Bouvier d'yvoire,3 X. Barbaut,1,2 N. Bleyzac,1 and R. W. Jelliffe2

ADCAPT, Department of Pharmacy, Hospital Antoine Charial, Francheville,1 and Hoechst-Marion-Roussel Co., Paris,3 France, and Laboratory of Applied Pharmacokinetics, University of Southern California School of Medicine, Los Angeles, California2

Received 24 January 1997/Returned for modification 20 June 1997/Accepted 3 May 1998

Various suggestions have been made for empirical pharmacodynamic indices of antibiotic effectiveness, such as areas under the drug concentration-time curve in serum (AUC), AUC>MIC, AUC/MIC, area under the inhibitory curve (AUIC), AUC above MIC, and time above MIC (T>MIC). In addition, bacterial growth and killing models, such as the Zhi model, have been developed. The goal of the present study was to compare the empirical behavior of the Zhi model of bacterial growth and killing with the other empirical pharmacodynamic indices described above by using simulated clinical data analyzed with the USC*PACK PC clinical programs for adaptive control of drug therapy, with one model describing a concentration-dependent antibiotic (tobramycin) and another describing a concentration-independent antibiotic (ticarcillin). The computed relative number of CFU was plotted against each pharmacodynamic index, with each axis parameterized over time. We assumed that a good pharmacodynamic index should present a clear and continuous relationship between the time course of its values and the time course of the bacterial killing as seen with the Zhi model. Preliminary work showed that some pharmacodynamic indices were very similar. A good sensitivity to the change in the values of the MIC was shown for AUC/MIC and also for T>MIC. In addition, the time courses of some other pharmacodynamic indices were very similar. Since AUC/MIC is easily calculated and shows more sensitivity, it appeared to be the best of the indices mentioned above for the concentration-dependent drug, because it incorporated and used the MIC the best. T>MIC appeared to be the best index for a concentration-independent drug. We also propose a new composite index, weighted AUC (WAUC), which appears to be useful for both concentration-dependent and concentration-independent drugs.

* Corresponding author. Mailing address: ADCAPT, Service Pharmaceutique, Hôpital Antoine Charial, 40 avenue de la Table de Pierre, 69340 Francheville, France. Phone: (33) 04-72-32-34-87. Fax: (33) 04-72-32-39-08. E-mail: adcapt{at}cismsum.univ-lyon1.fr.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1731-1737, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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