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PK / PD parameters
To calculate PK /PD parameters:
Please note: until a dose and interval has been correctly entered, this option is disabled.
Enter the MIC then click the Calculate button to determine the following antibiotic PK/PD parameters:
Click the Save button to save the calculated Pk/PD parameters, which will then be automatically printed on the consult.
Pk parameters quantify the serum level time course of an antibiotic. The three pharmacokinetic parameters that are most important for evaluating antibiotic efficacy are the peak serum level (Cmax), the trough level (Cmin), and the Area Under the serum concentration time Curve (AUC). While these parameters quantify the serum level time course, they do not describe the killing activity of an antibiotic.
The primary measure of antibiotic activity is the minimum inhibitory concentration (MIC). The MIC is the lowest concentration of an antibiotic that completely inhibits the growth of a microorganism in vitro. While the MIC is a good indicator of the potency of an antibiotic, it indicates nothing about the time course of antimicrobial activity.
Integrating the Pk parameters with the MIC gives us three Pk/PD parameters which quantify the activity of an antibiotic:
For Type I antibiotics (aminoglycosides, fluoroquinolones, daptomycin and the ketolides), the ideal dosing regimen would maximize concentration, because the higher the concentration, the more extensive and the faster is the degree of killing. Therefore, the 24h-AUC/MIC ratio, and the Peak/MIC ratio are important predictors of antibiotic efficacy. For aminoglycosides, it is best to have a Peak/MIC ratio of at least 8-10 to prevent resistence. For fluoroquinolones vs gram negative bacteria, the optimal 24h-AUC/MIC ratio is approximately 125. For gram positives bacteria, 40 appears to be optimal. However, the ideal 24h-AUC/MIC ratio for FQ's varies widely in the literature as research continues to define the optimal target.
Type II antibiotics (beta-lactams, clindamycin, erythromcyin, and linezolid) demonstrate the complete opposite properties. The ideal dosing regimen for these antibiotics maximizes the duration of exposure. The T>MIC is the parameter that best correlates with efficacy. For beta-lactams and erythromycin, maximum killing is seen when the time above MIC is at least 70% of the dosing interval.
Type III antibiotics (vancomycin, tetracyclines, azithromycin, and the dalfopristin-quinupristin combination) have mixed properties, they have time-dependent killing and moderate persistent effects. The ideal dosing regimen for these antibiotics maximizes the amount of drug received. Therefore, the 24hr-AUC/MIC ratio is the parameter that correlates with efficacy. For vancomycin, a 24hr-AUC/MIC ratio of at least 400 is necessary to ensure efficacy.
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