TABLE 3.
Doses and PD indices associated with a net static effect of anidulafungin against multiple Candida organisms in a murine neutropenic disseminated candidiasis modela
| Strain | Static dose (mg/kg/24 h) | Cmax/MIC | F1 Cmax/MIC | F2 Cmax/MIC | AUC0-24/MIC | F1 AUC0-24/MIC | F2 AUC0-24/MIC |
|---|---|---|---|---|---|---|---|
| C. albicans K-1 | 1.25 | 9 (72) | 0.09 (0.72) | 1.89 (14.4) | 200 (1,600) | 2.0 (16) | 42 (320) |
| C. albicans 98-17 | 1.15 | 42 (165) | 0.42 (1.65) | 8.66 (33) | 184 (736) | 1.84 (7.37) | 38.6 (147) |
| C. albicans 98-210 | 3.37 | 48 (193) | 0.48 (1.93) | 10.2 (39) | 1,078 (4,313) | 10.8 (43.1) | 226 (863) |
| C. albicans 580 | 0.94 | 27 (53) | 0.27 (0.53) | 5.6 (10.7) | 600 (1,200) | 6.0 (12) | 126 (240) |
| C. tropicals 98-234 | 3.81 | 27 (216) | 0.27 (2.16) | 5.4 (43.2) | 610 (4,880) | 6.1 (48.8) | 122 (976) |
| C. glabrata 570 | 1.97 | 14 (57) | 0.14 (0.57) | 2.97 (11.3) | 315 (1,260) | 3.15 (12.6) | 66.2 (252) |
| C. glabrata 513 | 2.45 | 18 (35) | 0.18 (0.35) | 3.69 (7.0) | 392 (783) | 3.92 (7.83) | 82.3 (157) |
| C. glabrata 33609 | 2.00 | 14 (57) | 0.14 (0.57) | 2.86 (11.5) | 317 (1,267) | 3.17 (12.7) | 63.4 (253) |
| C. glabrata 32930 | 1.58 | 11.3 (23) | 0.11 (0.23) | 2.26 (4.53) | 250 (500) | 2.5 (5.0) | 50 (100) |
| C. glabrata 33616 | NA | NA | NA | NA | NA | NA | |
| C. glabrata 34341 | 6.9 | 6.9 (58) | 0.07 (0.58) | 1.38 (11.5) | 132 (1,100) | 1.32 (11) | 26.4 (220) |
| C. glabrata 37661 | NA | NA | NA | NA | NA | NA | |
| C. glabrata 35315 | 6.4 | 6.2 (25) | 0.06 (0.25) | 1.24 (4.96) | 123 (492) | 1.23 (4.92) | 24.6 (98.4) |
| C. glabrata 5592 | 3.57 | 25 (50) | 0.25 (0.50) | 5.0 (10) | 570 (1,141) | 5.7 (11.4) | 114 (228) |
| C. glabrata 5376 | 6.8 | 92 (183) | 0.92 (1.83) | 18.3 (36.7) | 2,033 (4,047) | 20.3 (40.6) | 407 (813) |
| Mean ± SD | 26.1 ± 22 (91 ± 70) | 0.26 ± 0.22 (0.91 ± 0.70) | 5.47 ± 4.94 (18 ± 14) | 523 ± 521 (1,795 ± 1,538) | 5.23 ± 5.01 (18 ± 15) | 108 ± 110 (359 ± 307) |
a
NA indicates that the end point was not achieved. The static dose is the dose needed to maintain the organism burden at the same level as that at the start of therapy. F1 and F2 indicate that values were determined using free-drug concentrations of 1 and 20%, respectively. Values in parentheses are those determined using the partial-inhibition end point; other values were calculated using the complete-inhibition end point.