Table 2.
MSW-derived PD indices of polymyxin B alone and in combination against A. baumannii strains.
| Strain | Polymyxin B dosage regimena | Monotherapy | Double-combination of polymyxin B regimen/2 g q8h meropenemb | Triple-combination of polymyxin B regimen/2 g q8h meropenem/8 g q8h fosfomycinb | |||
|---|---|---|---|---|---|---|---|
| %TMSWc | %T>MPCc | %TMSW | %T>MPC | %TMSW | %T>MPC | ||
| ATCC 19606 | 1 mg/kg q12h | 12.5 ± 12.7 | 0.23 ± 1.26 | 0 | 48.7 ± 19.3 | 0 | 48.7 ± 19.3 |
| 1.5 mg/kg q12h | 68.1 ± 31.1 | 14.5 ± 24.8 | 0 | 96.0 ± 11.5 | 0 | 96.0 ± 11.5 | |
| LD plus 0.5 mg/kg q12h | 22.0 ± 12.7 | 2.94 ± 4.82 | 0 | 56.9 ± 19.7 | 0 | 56.9 ± 19.7 | |
| LD plus 1 mg/kg q12h | 57.5 ± 29.5 | 6.75 ± 14.5 | 0 | 97.6 ± 6.7 | 0 | 97.6 ± 6.7 | |
| LD plus 100 mg q12h | 27.6 ± 13.6 | 4.25 ± 6.6 | 0 | 64.4 ± 19.4 | 0 | 64.4 ± 19.4 | |
| Ac-PMBs/Mi | 1 mg/kg q12h | 10.8 ± 16.2 | NC | 0 | 94.1 ± 15.7 | 0 | 94.1 ± 15.7 |
| 1.5 mg/kg q12h | 24.4 ± 25.8 | 0.1 ± 1.1 | 0 | 98.2 ± 8.08 | 0 | 98.2 ± 8.08 | |
| LD plus 0.5 mg/kg q12h | 34.1 ± 31.2 | 1.2 ± 4.8 | 0 | 99.3 ± 4.8 | 0 | 99.3 ± 4.8 | |
| LD plus 1 mg/kg q12h | 40.3 ± 33.9 | 1.3 ± 4.2 | 0 | 99.6 ± 3.5 | 0 | 99.6 ± 3.5 | |
| LD plus 100 mg q12h | 44.5 ± 34.3 | 1.5 ± 4.6 | 0 | 99.8 ± 2.6 | 0 | 99.8 ± 2.6 | |
| Ac-PMBs/Mr | 1 mg/kg q12h | 10.8 ± 16.3 | NC | 93.3 ± 15.8 | 0.8 ± 3.3 | 0 | 94.1 ± 15.7 |
| 1.5 mg/kg q12h | 24.5 ± 26.1 | NC | 93.6 ± 12.1 | 4.7 ± 9.8 | 0 | 98.2 ± 8.1 | |
| LD plus 0.5 mg/kg q12h | 35.4 ± 32.9 | NC | 89.2 ± 16.3 | 10.1 ± 16.0 | 0 | 99.3 ± 4.8 | |
| LD plus 1 mg/kg q12h | 41.7 ± 35.5 | NC | 87.2 ± 19.6 | 12.4 ± 19.4 | 0 | 99.6 ± 3.5 | |
| LD plus 100 mg q12h | 46.0 ± 35.8 | NC | 85.4 ± 20.8 | 14.3 ± 20.7 | 0 | 99.8 ± 2.6 | |
| Ac-PMBr/Mr | 1 mg/kg q12h | NC | NC | 35.2 ± 21.4 | 37.5 ± 31.6 | 0 | 94.1 ± 15.7 |
| 1.5 mg/kg q12h | NC | NC | 29.2 ± 23.3 | 58.5 ± 33.8 | 0 | 98.2 ± 8.1 | |
| LD plus 0.5 mg/kg q12h | NC | NC | 22.1 ± 25.0 | 71.6 ± 32.3 | 0 | 99.3 ± 4.8 | |
| LD plus 1 mg/kg q12h | NC | NC | 18.2 ± 26.0 | 77.9 ± 31.1 | 0 | 99.6 ± 3.5 | |
| LD plus 100 mg q12h | NC | NC | 15.5 ± 24.8 | 81.7 ± 29.0 | 0 | 99.8 ± 2.9 | |
MSW mutant selection window, MPC mutant prevention concentration, LD loading dose of 3.0 mg/kg, NC not computable because polymyxin B MIC is higher than maximum. Values reported as mean ± SD.
aAll regimens were 1-h infusions.
bMeropenem and fosfomycin regimens were administered as 3-h prolonged infusions.
cTMSW or T>MPC was calculated as the percentage of the first 24 h.