TABLE 3.
In vivo pharmacodynamic target identification of anidulafungin, caspofungin, and micafungin against C. albicans, C. glabrata, and C. parapsilosis in a neutropenic murine disseminated candidiasis model
| Drug | Organism | Mean ± SDa |
|||||
|---|---|---|---|---|---|---|---|
| Static dose (mg/kg/24 h) | Static dose 24-h AUC/MIC | Static dose 24-h fAUC/MIC | 1 log kill (mg/kg/24 h) | 1 log kill 24-h AUC/MIC | 1 log kill 24-h fAUC/MIC | ||
| Anidulafungin | C. albicans | 2.32 ± 1.48 | 2,782 ± 2116 | 27.8 ± 21.1 | 4.25 ± 8.17 | 9,125 ± 8,144 | 91 ± 81 |
| C. glabrata | 21.1 ± 33.5 | 1,366 ± 1100 | 13.7 ± 11.0 | 39 ± 39 | 3,188 ± 2,256 | 32 ± 23 | |
| C. parapsilosis | 51.0 ± 35 | 1,154 ± 1091 | 11.5 ± 10.9 | 47 ± 46 | 2,244 ± 2,384 | 22 ± 24 | |
| Caspofungin | C. albicans | 0.72 ± 1.51 | 748 ± 1,675 | 22.4 ± 50.2 | 2.91 ± 6.66 | 865 ± 1,831 | 25.9 ± 54.9 |
| C. glabrata | 0.33 ± 0.71 | 96.2 ± 96 | 2.9 ± 2.8 | 1.16 ± 2.15 | 450 ± 448 | 13.5 ± 13.4 | |
| C. parapsilosis | 3.56 ± 3.08 | 559 ± 879 | 16.8 ± 26.4 | 9.84 ± 7.40 | 1,185 ± 1,385 | 35.5 ± 41.5 | |
| Micafungin | C. albicans | 2.79 ± 0.65 | 5,299 ± 1,860 | 12.7 ± 4.8 | 5.63 ± 3.08 | 10,088 ± 5,416 | 25.2 ± 13.5 |
| C. glabrata | 2.47 ± 2.79 | 1,542 ± 1,252 | 3.90 ± 3.1 | 5.88 ± 6.33 | 3,778 ± 3,003 | 9.45 ± 8.24 | |
| C. parapsilosis | 32.3 ± 24.0 | 1,981 ± 1,439 | 4.95 ± 3.6 | 55.8 ± 23.9 | 3,090 ± 1,781 | 7.73 ± 4.45 | |
Comparisons were statistically significant as follows. Static dose C. albicans caspofungin versus micafungin and anidulafungin, P = 0.01 and 0.04, respectively. Static dose C. glabrata caspofungin versus micafungin and anidulafungin, P < 0.001 and P = 0.05, respectively. Static dose C. parapsilosis caspofungin versus micafungin and anidulafungin, P = 0.0001 and P = 0.04, respectively. 1 Log kill dose C. glabrata caspofungin versus micafungin and anidulafungin, P = 0.001 and 0.005, respectively. 1 Log kill dose C. parapsilosis caspofungin versus micafungin and anidulafungin, P = 0.0001 and 0.001, respectively. Caspofungin static dose C. parapsilosis versus C. albicans and C. glabrata, P = 0.01 and 0.003, respectively. Caspofungin 1 log kill dose C. parapsilosis versus C. albicans and C. glabrata, P = 0.03 and 0.002, respectively. Anidulafungin static dose C. parapsilosis versus C. albicans and C. glabrata, P = 0.002 and 0.03, respectively. Micafungin static dose C. albicans versus C. parapsilosis and C. glabrata, P = 0.001 and P < 0.001, respectively. Micafungin 1 log kill dose C. albicans versus C. parapsilosis and C. glabrata, P < 0.001 and P < 0.001, respectively. tAUC/MIC static dose C. albicans anidulafungin versus caspofungin, P = 0.03; micafungin versus caspofungin, P < 0.001. tAUC/MIC static dose C glabrata anidulafungin versus caspofungin, P = 0.01; micafungin versus caspofungin, P = 0.001. tAUC/MIC static dose C parapsilosis micafungin versus caspofungin, P = 0.001. tAUC/MIC anidulafungin C. albicans versus C. parapsilosis, P = 0.01. tAUC/MIC 1 log kill anidulafungin C. albicans versus C. glabrata and C. parapsilosis, P = 0.01 and 0.001, respectively. fAUC static dose C. glabrata anidulafungin versus caspofungin and micafungin, P = 0.002 and 0.005, respectively. fAUC/MIC 1 log kill dose C. glabrata anidulafungin versus caspofungin and micafungin, P = 0.007 and 0.02, respectively. fAUC/MIC 1 log kill dose C. parapsilosis caspofungin versus micafungin, P = 0.009. fAUC/MIC static dose micafungin C. albicans versus C. glabrata and C. parapsilosis, P < 0.001 and P < 0.001, respectively. fAUC/MIC 1 log kill micafungin C. albicans versus C. glabrata and C. parapsilosis, P < 0.001 and P < 0.001, respectively.