Table 3.
Effects of 1.4 mg/kg/day of DAMB alone or in combination with three dosages of the Mycograb C28Y variant on the fungal densities in the kidneys, livers, and spleens of neutropenic mice with systemic candidiasis
| Organ | Exptl group | Fungal density (log CFU/g ± SD) after indicated duration (h) of treatmenta |
|||
|---|---|---|---|---|---|
| 0 | 24 | 72 | 120 | ||
| Kidney | No-treatment control | 3.52 ± 0.15 (3) | 5.34 ± 0.22 (5) | 5.64 ± 0.18b (10) | |
| Vehicle control | 5.23 ± 0.08 (5) | 5.71 ± 0.27b (13) | |||
| Myc-C28Y, 15 mg/kg/day control | 5.31 ± 0.09 (5) | 5.83 ± 0.28b (13) | |||
| DAMB alone | 4.18 ± 0.12c (5) | 4.29 ± 0.16d (5) | 4.15 ± 0.46d (5) | ||
| DAMB + vehicle | 4.24 ± 0.05c (5) | 4.33 ± 0.31d (5) | 4.19 ± 0.48d (8) | ||
| DAMB + Myc-C28Y at 0.15 mg/kg/day | 4.29 ± 0.16c (5) | 4.19 ± 0.48d (5) | 3.94 ± 0.43d (7)e | ||
| DAMB + Myc-C28Y at 1.5 mg/kg/day | 3.96 ± 0.20c (5) | 4.26 ± 0.37d (5) | 4.03 ± 0.74d (8) | ||
| DAMB + Myc-C28Y at 15 mg/kg/day | 3.74 ± 0.64c (5) | 4.41 ± 0.14d (5) | 3.95 ± 0.64d (8) | ||
| Liver | No-treatment control | 3.81 ± 0.05 (3) | 3.83 ± 0.10 (5) | 3.75 ± 0.21b (10) | |
| Vehicle control | 3.73 ± 0.11 (5) | 3.80 ± 0.23b (13) | |||
| Myc-C28Y, 15 mg/kg/day control | 3.63 ± 0.16 (5) | 3.98 ± 0.36b (13) | |||
| DAMB alone | 2.91 ± 0.42c (5) | 1.18 ± 0.67d (5) | 0.28 ± 0.63d (5) | ||
| DAMB + vehicle | 2.69 ± 0.46c (5) | 1.55 ± 0.90d (5) | 0.81 ± 0.92d (8) | ||
| DAMB + Myc-C28Y at 0.15 mg/kg/day | 2.80 ± 0.44c (5) | 1.06 ± 1.00d (5) | 0.44 ± 0.76d (7)e | ||
| DAMB + Myc-C28Y at 1.5 mg/kg/day | 2.78 ± 0.44c (5) | 1.36 ± 1.35d (5) | 0.83 ± 1.20d (8) | ||
| DAMB + Myc-C28Y at 15 mg/kg/day | 2.53 ± 0.66c (5) | 1.02 ± 0.95d (5) | 0.45 ± 0.83d (8) | ||
| Spleen | No-treatment control | 3.05 ± 0.17 (3) | 3.89 ± 0.28 (5) | 4.05 ± 0.34b (10) | |
| Vehicle control | 3.65 ± 0.34 (5) | 4.12 ± 0.60b (13) | |||
| Myc-C28Y, 15 mg/kg/day control | 3.60 ± 0.15 (5) | 4.04 ± 0.27b (13) | |||
| DAMB alone | 3.21 ± 0.27 (5) | 2.36 ± 0.19d (5) | 1.52 ± 0.87d (5) | ||
| DAMB + vehicle | 3.32 ± 0.24 (5) | 2.67 ± 0.42d (5) | 2.01 ± 0.90d (7)g | ||
| DAMB + Myc-C28Y at 0.15 mg/kg/day | 3.15 ± 0.52 (5) | 2.66 ± 0.16d (5) | 1.32 ± 0.92d (7)e | ||
| DAMB + Myc-C28Y at 1.5 mg/kg/day | 2.93 ± 0.25f (5) | 3.01 ± 0.74d (5) | 2.15 ± 0.55d (8) | ||
| DAMB + Myc-C28Y at 15 mg/kg/day | 2.77 ± 0.82f (5) | 2.65 ± 0.29d (5) | 2.23 ± 0.23d (8) | ||
Numbers in parentheses are the numbers of animals evaluated at each time point.
The 72- and 120-h controls were sacrificed at 48 h because of progressive disease. They were recorded with the 72-h data groups. There were three additional animals in all groups that received vehicle or the antibody fragment by the intravenous route, to increase the probability that at least five mice could be evaluated at the last time point in which the mice in that group survived. This accounts for the higher number of animals at the last evaluable time point in these groups.
The DAMB, DAMB plus vehicle, and the three DAMB plus Myc-C28Y treatment groups were statistically significantly different from the three control groups at 24 h (P < 0.05) but were different from each other (Tukey-Kramer test for multiple comparisons).
The DAMB, DAMB plus vehicle, and the three DAMB plus Myc-C28Y treatment groups were statistically significantly different from the three 72-h control groups (based on the Tukey-Kramer test for multiple comparisons).
One mouse in the DAMB plus Myc-C28Y at 0.15 mg/kg/day group did not receive a full dose of the antibody fragment on day 4 of treatment and was therefore removed from the study.
The DAMB plus Myc-C28Y at 1.5 or 15 mg/kg/day groups were statistically significantly different from the no-treatment controls at 24 h based on the Tukey-Kramer test for multiple comparisons. The DAMB plus Myc-C28Y at 15 mg/kg/day regimen was also statistically different from the vehicle control group at this time point based on the Tukey-Kramer test.
One mouse in this group did not have a spleen. Thus, only 7 of 8 mice in this group were assessed for fungal densities in spleens.