Table 3.

Efficacy of delayed therapy against disseminated C. albicans MY1055 infection in ICR mice with CY-induced, chronic immunosuppressiona

CompoundDose (mg/kg)Log10CFU/g kidneys (% sterilizationb [% reduction from control]c) at time point after challenge
Day 4Day 8Day 14Day 21Day 28
Caspofungin1.003.64* ± 0.18 (0 [99.85])2.30* ± 0.83 (90 [99.98])2.07* ± 0.07 (70 [99.99])2.07* ± 0.07 (100 [99.99])2.09* ± 0.08 (100 [99.99])
0.503.94* ± 0.28 (0 [99.70])2.10* ± 0.04 (100 [99.99])2.06* ± 0.06 (100 [99.99])2.08* ± 0.08 (100 [99.99])2.10* ± 0.05 (90 [99.99])
0.254.34* ± 0.34 (0 [99.26])2.10* ± 0.15 (90 [99.99])2.78* ± 0.96 (60 [99.97])3.44* ± 1.66 (50 [99.68])3.80* ± 1.74 (40 [99.93])
AmB1.005.09* ± 0.80 (0 [95.82])2.07* ± 0.07 (80 [99.99])2.46* ± 0.79 (60 [99.98])2.37* ± 0.82 (80 [99.97])3.41* ± 2.11 (80 [99.97])
0.505.63* ± 0.92 (0 [85.49])2.91* ± 0.49 (60 [99.93])2.93* ± 1.00 (50 [99.95])3.47* ± 1.40 (20 [99.66])4.14* ± 2.11 (40 [99.84])
0.256.20 ± 0.39 (0 [46.79])3.58* ± 0.51 (10 [99.67])4.08* ± 0.93 (10 [99.33])4.56 ± 1.30 (10 [95.78])4.44* ± 2.57 (50 [99.68])
FCZ80.005.57* ± 0.51 (0 [90.53])3.51* ± 1.35 (20 [99.87])4.37* ± 0.38 (0 [99.69])6.75 ± 0.91 (0 [NC]d)6.01 ± 2.26 (20 [NC])
40.005.91* ± 0.18 (0 [79.26])3.45* ± 0.30 (0 [99.89])5.35 ± 0.48 (0 [97.11])6.97 ± 0.41 (0 [NC])6.17 ± 2.36 (20 [NC])
20.005.70* ± 0.36 (0 [87.12])2.87 ± 0.59 (20 [99.97])5.22 ± 1.01 (0 [97.85])4.15 ± 2.01 (40 [NC])7.68 (0 [NC])
Sham treated6.47 ± 0.30 (0)6.06 ± 0.30 (0)6.26 ± 1.28 (0)5.94 ± 2.24 (0)6.93 ± 0.41 (0)
  • a Mice were challenged i.v. with C. albicans MY1055 at 5.6 × 104 CFU/mouse (study 1) and 1.22 × 105 CFU/mouse (study 2). Mice received the first treatment 24 h after challenge (delayed therapy) and were treated i.p., q.d., for 7 days. Mice were immunosuppressed throughout the experimental period (28 days). Kidneys were aseptically collected at days 4, 8, 14, 21, and 28 after challenge.

  • b Mean log10 CFU/gram ± standard deviation at time points after challenge for paired kidneys. There were 10 mice per group except as follows. For FCZ-treated mice, there were five mice per group, except for the 20-mg/kg dose at day 28 (one mouse). Groups of sham-treated mice contained eight, five, and two mice on days 14, 21, and 28, respectively. Percent sterilization indicates the number of mice with no detectable yeast, where the limit of detection was 50 yeast cells per pair of kidneys. Data for caspofungin are pooled from studies 1 and 2.

  • c Percent reduction calculated based on reduction in CFU/g of kidneys of treated groups compared to sham-treated control animals.

  • d NC, not calculated.

  • e *, significantly different from result for sham-treated control (P < 0.05; Excel ttest).