Fig. 3.

Deterministic PK/PD estimates for a 10 day period: an example. a As in the references, asterisks denote calculated concentrations 1 h after each dose (simulated as a 5-min infusion). For the dosing regimen in this example, peak and trough concentrations are predicted to decrease. b Most bacteria are predicted to acquire reversible adaptive drug resistance within 10 h after the first dose. In addition, the drug clearance gradually increases during the 10-day period. Both factors tend to make later doses less effective than early ones. c This panel illustrates some key properties. First, deterministic PK/PD models sometimes predict that the average total CFU number in S becomes less than 1. Here, the minimum (at time z) is only about 0.255 CFU per patient. Second, we here have u < 36 h for the time u where the predicted CFU number is less than 100 for the last time. Third, a simplified model, in which the rate ksr = 0, is very nearly exact until a time greater than u when the predicted CFU number has grown very large. Such properties facilitate the comparison of stochastic to deterministic PD predictions (see text)