TABLE 3.
Studies evaluating the fAUC/MIC targets of polymyxins with different magnitudes of bacterial killing
| Experimental Model | Species | Antibiotic | PK/PD Index | PK/PD Target |
|---|---|---|---|---|
| IVM (Bergen et al., 2010) | P. aeruginosa (n = 3) | Colistin | fAUC/MIC | 1-log10 kill: 5.04–27.1 |
| 2-log10 kill: 6.81–35.7 | ||||
| Neutropenic mouse thigh infection model (Cheah et al., 2015) | P. aeruginosa (n = 3) | Colistin (subcutaneous administration) | fAUC/MIC | Plasma |
| Stasis: 6.0–8.7 | ||||
| 1-log10 kill: 6.6–10.9 | ||||
| 2-log10 kill: 7.4–13.7 | ||||
| Neutropenic mouse lung infection model (Cheah et al., 2015) | P. aeruginosa (n = 3) | Colistin (subcutaneous administration) | fAUC/MIC | Plasma |
| Stasis: 15.2–38.6 | ||||
| 1-log10 kill: 43.3–57.9 | ||||
| 2-log10 kill: 51.8–105 | ||||
| Neutropenic mouse lung infection model (Lin et al., 2017b) | P. aeruginosa (n = 3) | Colistin (pulmonary administration) | AUC/MIC, fAUC/MIC | ELF (AUC/MIC) |
| Stasis: 684–1050 | ||||
| 1-log10 kill: 796–1236 | ||||
| Plasma (fAUC/MIC) | ||||
| Stasis: 2.15–3.29 | ||||
| 1-log10 kill: 2.6–4.68 | ||||
| Neutropenic mouse lung infection model (Lin et al., 2017a) | P. aeruginosa (n = 3) | Polymyxin B (pulmonary administration) | AUC/MIC, fAUC/MIC | ELF (AUC/MIC) |
| Stasis: 1326–1506 | ||||
| 1-log10 kill: 1453–1922 | ||||
| 2-log10 kill: 1693–1778 | ||||
| Plasma (fAUC/MIC) | ||||
| Stasis: 3.14–4.03 | ||||
| 1-log10 kill: 3.73–5.24 | ||||
| 2-log10 kill: 4.49–6.7 | ||||
| Biofilm lung infection model (Hengzhuang et al., 2012) | P. aeruginosa (n = 1) | Colistin (intraperitoneal administration) | AUC/MIC | Serum |
| Stasis: 167 (planktonic), 500 (biofilm) | ||||
| 1-log10 kill: 297 (planktonic), 867 (biofilm) | ||||
| 2-log10 kill: 433 (planktonic), 867 (biofilm) | ||||
| Neutropenic mouse thigh infection model (Cheah et al., 2015) | A. baumannii (n = 3) | Colistin (subcutaneous administration) | fAUC/MIC | Plasma |
| Stasis: 1.4–9.3 | ||||
| 1-log10 kill: 3.5–13.9 | ||||
| 2-log10 kill: 7.4–17.6 | ||||
| Neutropenic mouse lung infection model (Cheah et al., 2015) | A. baumannii (n = 1a) | Colistin (subcutaneous administration) | fAUC/MIC | Plasma |
| Stasis: 11.6 | ||||
| 1-log10 kill: 20.8 | ||||
| 2-log10 kill: 36.8 | ||||
| Neutropenic mouse lung infection model (Lin et al., 2018) | A. baumannii (n = 3) | Colistin (pulmonary administration) | AUC/MIC, fAUC/MIC | ELF (AUC/MIC) |
| Stasis: 326–989 | ||||
| 1-log10 kill: 430–1213 | ||||
| 2-log10 kill: 540–1404 | ||||
| Plasma (fAUC/MIC) | ||||
| Stasis: 0.86–2.18 | ||||
| 1-log10 kill: 1.2–3.29 | ||||
| 2-log10 kill: 1.58–4.45 | ||||
| Neutropenic mouse thigh infection model (Landersdorfer et al., 2018) | K. pneumoniae (n = 3) | Polymyxin B (subcutaneous administration) | fAUC/MIC | Plasma |
| Stasis: 1.22–13.5 | ||||
| 1-log10 kill: 3.72–28 | ||||
| Neutropenic mouse lung infection model (Lin et al., 2018) | K. pneumoniae (n = 3) | Colistin (pulmonary administration) | AUC/MIC, fAUC/MIC | ELF (AUC/MIC) |
| Stasis: 525–2924 | ||||
| 1-log10 kill: 597b | ||||
| 2-log10 kill: 866b | ||||
| Plasma (fAUC/MIC) | ||||
| Stasis: 1.34–6.62 | ||||
| 1-log10 kill: 1.74b | ||||
| 2-log10 kill: 2.44b |
a
Only one isolate was included, as stasis was not achieved with the highest tolerable dose of colistin against the other two isolates.
b
Determined with only one isolate.