COMPARISONS BETWEEN ANTIMICROBIAL PHARMACODYNAMIC INDEXES AND BACTERIAL KILLING AS DESCRIBED BY USING THE ZHI MODEL

Various suggestions have been made for empirical pharmacodynamic indic es of antibiotic effectiveness, such as areas under the drug concentra tion-time curve in serum (AUC), AUC > MIC, AUC/MIC, area under the inh ibitory curve (AUIC), AUC above MIG, 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 wi th the other empirical pharmacodynamic indices described above by usin g simulated clinical data analyzed with the USCPACK PC clinical progr ams 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 re lative number of CFU was plotted against each pharmacodynamic index, w ith each axis parameterized over time. We assumed that a good pharmaco dynamic index should present a clear and continuous relationship betwe en 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 c hange 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 indic es were very similar. Since AUC/MIC is easily calculated and shows mor e sensitivity, it appeared to be the best of the indices mentioned abo ve for the concentration-dependent drug, because it incorporated and u sed the MIC the best. T > MIC appeared to be the best index for a conc entration-independent drug. We also propose a new composite index, wei ghted AUC (WAUC), which appears to be useful for both concentration-de pendent and concentration-independent drugs.