Table 2.
Parameter estimates for mechanism-based PD model.
| Parameter | Definition | Units | Estimate (%RSEa) |
|---|---|---|---|
| Pharmacokinetic parameters | |||
| CLD,PYO | Distributional clearance of PYO2b | mL/h | 2.96 (20.2%) |
| CLD,215 | Distributional clearance of E215b | mL/h | 3.66 (19.4%) |
| CLD,LUZ | Distributional clearance of LUZ19b | mL/h | 2.42 (13.9%) |
| Bacterial-specific parameters | |||
| LGCFUMX | System maximum capacityb | log10 (CFU/mL) | 9.69 (0.603%) |
| γ | Shape parameter for logistic growthc | – | 0.1 (FIXED) |
| LGINOC | Starting inoculumb | log10 (CFU/mL) | 5.46 (1.64%) |
| MGTS | Mean generation time for susceptible- or single phage-resistant subpopulationb | min | 23.1 (3.73%) |
| MGTR | Mean generation time for double phage-resistant subpopulationb | min | 56.6 (4.36%) |
| Shared phage parameters | |||
| LGRr | Log-transformed 1st order rate constant for adaptive resistance to all three phagesc | log10 (1/h) | −8.60 (0.694%) |
| LGEC50 | Log-transformed concentration for virocells-induced resistance/collateral phage effectsc | log10 (CFU/mL) | 2 (FIXED) |
| hrst | Shape parameter for virocells-induced effectsc | – | 5 (FIXED) |
| LGKrev | Log-transformed 1st order rate constant for reversion of resistant cells to susceptiblec | log10 (1/h) | −2.75 (3.52%) |
| PYO2-specific parameters | |||
| LGKpyo | Log-transformed 2nd order rate constant for phage-bacteria bindingc | log10 (mL/PFU/h) | −9.64 (0.582%) |
| LGRpyo | Log-transformed 1st order rate constant for single-phage adaptive resistancec | log10 (1/h) | −15 (FIXED) |
| τ pyo | Mean transit time for virocells maturationb | min | 20.4 (21.2%) |
| N pyo | PYO2 burst sizeb | PFU/CFU | 73.8 (25.1%) |
| E215-specific parameters | |||
| LGK215 | Log-transformed 2nd order rate constant for phage-bacteria bindingc | log10 (mL/PFU/h) | −9.48 (0.0968%) |
| LGR 215 | Log-transformed 1st order rate constant for single-phage adaptive resistancec | log10 (1/h) | −6.17 (7.56%) |
| τ 215 | Mean transit time for virocells maturationb | min | 31.7 (13.6%) |
| N 215 | PYO2 burst sizeb | PFU/CFU | 168 (12.5%) |
| Emax,EoL | Maximum effect of E215 on LUZ19 adsorption ratec | – | 4.46 (5.82%) |
| LUZ19-specific parameters | |||
| LGKluz | Log-transformed 2nd order rate constant for phage-bacteria bindingc | log10 (mL/PFU/h) | −8.43 (0.0973%) |
| LGRluz | Log-transformed 1st order rate constant for single-phage adaptive resistancec | log10 (1/h) | −5.68 (4.68%) |
| τ luz | Mean transit time for virocells maturationb | min | 27.9 (8.69%) |
| N luz | PYO2 burst sizeb | PFU/CFU | 83.0 (18.0%) |
| Emax,LoE | Maximum effect of LUZ19 on E215 adsorption ratec | – | 8.48 (13.3%) |
| Emax,LoP | Maximum effect of LUZ19 on PYO2 adsorption ratec | – | 1.41 (15.9%) |
| Residual variability | |||
| aPAO1 | Constant residual variability for PAO1 | log10 (CFU/mL) | 0.83 (4.01%) |
| apyo2 | Constant residual variability for PYO2 in the HFIM cartridge | log10 (PFU/mL) | 1.85 (7.90%) |
| apyo2,cent | Constant residual variability for PYO2 in the central reservoir | log10 (PFU/mL) | 3.30 (6.94%) |
| aE215 | Constant residual variability for E215 in the HFIM cartridge | log10 (PFU/mL) | 2.34 (6.57%) |
| aE215,cent | Constant residual variability for E215in the central reservoir | log10 (PFU/mL) | 2.33 (6.80%) |
| aLUZ19 | Constant residual variability for LUZ19 in the HFIM cartridge | log10 (PFU/mL) | 1.67 (5.61%) |
| aLUZ19,cent | Constant residual variability for LUZ19 in the central reservoir | log10 (PFU/mL) | 2.17 (5.39%) |
a
RSE% – residual standard error percent.
b
IIV fixed to ω = 0.05.
c
IIV fixed to ω = 0.