TABLE 6.
Correlation between results of the mouse whole-blood assay and in vivo response for SMC-3176 against P. aeruginosa
| Isolate | MIC (mg/liter) in: |
MIC shift in mouse WB assaya | In vivo response | |||
|---|---|---|---|---|---|---|
| MHB | CDMHB | LB CO2 | Mouse WB CO2 | |||
| PAO1 | 0.25 | 0.12 | 0.25, 0.25, 0.25, 0.25 | 0.25, 0.25, 0.5, 0.5 | 2-fold increase | Efficacy predicted by MIC |
| ARC3502 | 0.12 | 0.25 | 0.25, 0.25, 0.25, 0.5 | 1, 2, 2, 4 | 8-fold increase | Efficacy predicted by MIC |
| ARC3506 | 0.12 | 0.25 | 0.25, 0.25, 0.5 | 2, 2, 2 | 8-fold increase | Efficacy predicted by MIC |
| ARC4659 | 8 | 0.5 | 8, 8, 8, 16 | 2, 2, 2, 2 | 4-fold decrease | Efficacy predicted by MIC |
| AZ 8-18 | 0.5 | 0.25 | 0.12, 0.25, 0.25 | 0.5, 0.5, 0.5 | 2-fold increase | Not tested |
| AZ 32-13b | 0.5 | 0.5 | 0.5, 0.5, 0.5 | 8, 16, 16 | ≥16-fold increase | Not tested |
| JJ 4-36b | 0.12 | 0.06 | 0.06, 0.12, 0.12, 0.12 | 2, 2, 2, 4 | ≥16-fold increase | Efficacy not predicted by MIC |
| JJ 5-35b | 0.5 | 0.12 | 0.25, 0.25, 0.5 | 4, 8, 16 | ≥16-fold increase | Not tested |
| JJ 8-16b | 0.12 | 0.06 | 0.25, 0.25, 0.5, 0.5 | 4, 8, 8, 16 | ≥16-fold increase | Not tested |
| JJ 11-54b | 0.5 | 0.25 | 0.25, 0.5, 0.5, 0.5 | 4, 8, 8, 8 | ≥16-fold increase | Not tested |
a
Assay results interpreted by the fold increase between the modal or central MIC in LB CO2 and the modal or central MIC in mouse WB CO2 from three or more independent tests.
b
Isolates against which in vivo failures were previously reported for siderophore-conjugated monobactam MB-1 (11).