TABLE 3.
Pharmacodynamic model parameter estimatesa
| Parameter | Abbreviation | Mean CTAP23 (SD) | Mean CTAP40 (SD) |
|---|---|---|---|
| Susceptible growth rate constant (log10 CFU/ml/h) | Kgs | 1.31 (0.11) | 1.08 (0.20) |
| Intermediate growth rate constant (log10 CFU/ml/h) | Kgr | 0.40 (0.13) | 0.60 (0.26) |
| Resistant growth rate constant (log10 CFU/ml/h) | Kgrr | 0.69 (0.11) | 0.55 (0.13) |
| Central compartment HFIM vol (liters) | Vc | 0.32 (0.01) | 0.26 (0.05) |
| Amikacin clearance (liters/h) | Cl | 0.03 (0.00) | 0.03 (0.00) |
| Susceptible killing rate constant (log10 CFU/ml/h) | Emax,s | 5.34 (1.50) | 4.00 (3.01) |
| Intermediate killing rate constant (log10 CFU/ml/h) | Emax,r | 9.43 (3.19) | 11.20 (2.10) |
| Amikacin conc. causing 50% Emax,s (mg/liter) | EC50s | 11.61 (3.49) | 11.10 (2.53) |
| Amikacin conc. causing 50% Emax,r (mg/liter) | EC50r | 244.09 (149.73) | 349.63 (79.19) |
| Susceptible Hill coefficient | Hs | 6.00 (4.27) | 11.04 (5.80) |
| Resistant Hill coefficient | Hr | 3.42 (2.47) | 7.71 (2.61) |
| Intermediate population initial condition (CFU/ml) | ICRe | 211.05 (119.12) | 320.48 (50.57) |
| Resistant population initial condition (CFU/ml) | ICRRe | 29.46 (48.23) | 25.81 (16.70) |
| Maximum substrate consumption | Qmax | 0.81 (0.18) | 0.59 (0.29) |
| Maximum available substrate | Substrate | 3.33 × 1010 (2.22 × 1010) | 4.92 × 1010 (2.75 × 1010) |
| Substrate conc. causing 50% Qmax | Qs | 8.15 × 105 (9.61 × 104) | 5.3 × 105 (1.69 × 105) |
| Death rate constant susceptible population | Kds | 0.25 (0.15) | 0.05 (0.04) |
| Death rate constant intermediate population | Kdi | 0.24 (0.18) | 0.02 (0.03) |
| Death rate constant resistant population | Kdr | 0.03 (0.02) | 0.11 (0.32) |
a
The mean and standard deviation (SD) for each parameter and isolate were determined using the average and bootstrapped estimates, respectively, of the posterior model estimates for each dosing regimen.