Table 3.
In vivo activities of anidulafungin, caspofungin, and micafungin against fks mutant C. glabrata isolates in a neutropenic murine disseminated candidiasis model
| Antifungal agent and C. glabrata isolate no. | MIC (μg/ml) | Static dose (mg/kg/24 h) | 1-log kill (mg/kg/24 h) | AUCf/MIC based on: |
|
|---|---|---|---|---|---|
| Static dose | 1-log kill | ||||
| Anidulafungin | |||||
| CG 4747 | 0.06 | 1.31 | NAa | 4.19 | NA |
| CG 4720 | 4 | NA | NA | NA | NA |
| CG 10956 | 1 | 5.69 | NA | 1.09 | NA |
| CG 729 | 4 | NA | NA | NA | NA |
| CG 14378 | 2 | NA | NA | NA | NA |
| CG 211 | 1 | 18.8 | NA | 3.59 | NA |
| CG 760 | 1 | 34.9 | NA | 7.77 | NA |
| CG 2092 | 0.50 | 3.38 | 11.2 | 1.30 | 4.29 |
| CG 4742 | 0.25 | 3.45 | 17.6 | 2.65 | 13.5 |
| CG 33616 | 1 | NA | NA | NA | NA |
| CG 37661 | 2 | NA | NA | NA | NA |
| Meanb | 1.53 | 11.3 | 14.4 | 3.43 | 8.87 |
| Median | 1.00 | 4.57 | 14.4 | 3.12 | 8.87 |
| SD | 1.36 | 13.2 | 4.53 | 2.45 | 6.49 |
| Caspofungin | |||||
| CG 4747 | 1 | 0.25 | 0.43 | 0.25 | 0.42 |
| CG 4720 | 8 | 14.9 | NA | 1.06 | NA |
| CG 10956 | 2 | 2.38 | 20.3 | 1.17 | 5.20 |
| CG 729 | 16 | NA | NA | NA | NA |
| CG 14378 | 4 | NA | NA | NA | NA |
| CG 211 | 1 | 4.26 | 24.8 | 4.19 | 11.1 |
| CG 760 | 1 | 7.47 | 52.4 | 5.81 | 15.6 |
| CG 2092 | 1 | 0.36 | 0.81 | 0.36 | 0.79 |
| CG 4742 | 1 | 0.32 | 2.40 | 0.31 | 2.36 |
| CG 33616 | 0.25 | 2.08 | 6.64 | 8.19 | 22.1 |
| Meanb | 3.53 | 4.01 | 15.4 | 2.67 | 8.21 |
| Median | 1.00 | 2.23 | 6.64 | 1.12 | 5.20 |
| SD | 4.95 | 5.06 | 19.0 | 3.03 | 8.30 |
| Micafungin | |||||
| CG 4747 | 0.25 | 1.12 | 1.77 | 0.31 | 0.49 |
| CG 4720 | 4 | NA | NA | NA | NA |
| CG 10956 | 0.25 | 0.22 | 2.63 | 0.06 | 0.73 |
| CG 729 | 8 | NA | NA | NA | NA |
| CG 14378 | 2 | NA | NA | NA | NA |
| CG 211 | 0.25 | 4.83 | NA | 1.33 | NA |
| CG 760 | 0.25 | 4.24 | NA | 1.17 | NA |
| CG 2092 | 0.13 | 0.94 | 2.65 | 0.52 | 1.47 |
| CG 4742 | 0.50 | 1.30 | 10.28 | 0.18 | 1.36 |
| CG 33616 | 0.25 | 3.88 | 7.89 | 1.1 | 2.2 |
| CG 37661 | 0.25 | 9.25 | 20.60 | 2.5 | 5.2 |
| Meanb | 1.47 | 3.22 | 7.64 | 0.90 | 1.91 |
| Median | 0.25 | 2.59 | 5.27 | 0.81 | 1.41 |
| SD | 2.47 | 2.99 | 7.20 | 0.81 | 1.72 |
a
NA, not achieved.
b
There was not a statistical difference between the median static dose or 1-log kill free drug AUC/MIC target endpoint for any of the three drugs.