A Novel Approach to Pharmacodynamic Assessment of Antimicrobial Agents: New Insights to Dosing Regimen Design
Figure 2
Concentration dependent killing; AUC/MIC most important.
Kk = 60.0 h−1. C50 = 600.0 mg/l. H = 1.0. Black solid line depicts the relationship between drug concentration and killing rate; black dotted line represents the microbial growth rate. Arrows below represent concentration ranges achieved with various dosing regimens (red – once daily; green – twice daily; blue – four times daily). Two intersecting planes are shown: a translucent surface and an opaque mesh surface (where the average kill rate = 1.0 h−1). The 3-dimensional mesh surface is made up of a collection of data points; each datum point is characterized by a value on the x, y and z axes, corresponding to the daily dose (x), dosing interval (y) and average kill rate (z). For a dosing regimen to suppress resistance development, it is imperative that the average kill rate (D) is more than the growth rate (Kg) of the target pathogen. To identify promising dosing regimens (combinations of dose and dosing interval) to suppress resistance development, D must be greater than Kg (the region where the translucent surface is above the opaque mesh plane). White area depicts dosing regimens (combinations of daily dose and dosing interval which the average kill rate is >1.0 h−1. Using a daily dose of 6000 mg, the average kill rates for different regimens are: 1.463 h−1 (q24h), 1.610 h−1 (q12h), and 1.690 h−1(q6h).