Table 3.
Magnitude of Durlobactam fAUC0–24/MIC Associated With 1- and 2-Log10 CFU Reductions From Baseline and EC80 Based on Data From In Vitro and In Vivo Studies
| Model | No. of Isolates | r 2 | Durlobactam fAUC0–24/MIC by Endpoint | ||
|---|---|---|---|---|---|
| CFU Reduction From Baseline | EC80 | ||||
| 1-Log10 CFU Reduction | 2-Log10 CFU Reduction | ||||
| In vitro chemostata | 1 | 0.87 | 7.6 | 33.4 | NC |
| In vivo thigh (4:1 dose)b | 5 | 0.86 | 8.0 | 16.0 | 15.1 |
| In vivo lung (4:1 dose)c | 4 | 0.91 | 10.6 | 22.4 | 78.6 |
| In vivo thigh (fixed SUL dose)d | 6 | 0.82 | 7.5 | 31.8 | 38.2 |
| Mean ± SD | … | … | 8.4 ± 1.5 | 25.9 ± 8.2 | 44.0 ± 32.1 |
Data from reference (O'Donnell et al., Unpublished data). PK-PD analysis of 24-hour net CFU reduction vs fAUC0–24/MIC. EC80, the percentage of time required for unbound concentrations to remain above the MIC in order to achieve 80% of the maximum activity. Abbreviations: CFU, colony-forming units; fAUC0–24/MIC, ratio of unbound area under the concentration-time curve over 0 to 24 hours to the minimum inhibitory concentration; NC, not calculated; PK/PD, pharmacokinetic/pharmacodynamic; SD, standard deviation; SUL, sulbactam.
SUL exposure at >50% fT > MIC.
SUL mean exposure of 32.9% to 43.5% fT > MIC; sulbactam:durlobactam, 4:1.
SUL mean exposure of 43.9% to 81.5% fT > MIC; sulbactam:durlobactam, 4:1.
SUL exposure range of 18.2% to 52.7% fT > MIC; sulbactam dose held constant.