Table 1.
Inoculation method and tissue |
C. neoformans USC1597 fungal burden (log10 CFU/gram) by treatmenta |
||||||||
---|---|---|---|---|---|---|---|---|---|
Control | MTF (mg/kg) |
FLC | AMB | MTF (45 mg/kg) + FLC | MTF (45 mg/kg) + AMB | ||||
5 | 10 | 15 | 45 | ||||||
Intracranialb | |||||||||
Brain | 6.04 ± 0.51 | 5.57 ± 0.35 | 5.98 ± 0.51 | 5.61 ± 0.54 | 6.03 ± 0.42 | 2.64 ± 1.05* | 2.20 ± 0.92* | 3.32 ± 0.90* | 2.83 ± 1.32* |
Intravenousc | |||||||||
Lung | 7.22 ± 0.62 | 7.46 ± 0.28 | 5.77 ± 1.99** | 5.67 ± 1.61** | |||||
Brain | 6.23 ± 0.23 | 6.34 ± 0.15 | 4.35 ± 1.20* | 4.04 ± 1.02* |
MTF, miltefosine; FLC, fluconazole; AMB, amphotericin B. Values are means ± standard deviations. Fluconazole was administered at 10 mg/kg, and amphotericin B was administered at 3 mg/kg. * P < 0.001; **, P < 0.05 (versus untreated controls and all-miltefosine monotherapy).
In the cryptococcal meningoencephalitis model, antifungal therapy with miltefosine, fluconazole, or amphotericin B was continued through day 7, and brains were collected on day 8 for fungal burden quantification (n = 19 to 20 mice per group for untreated controls, fluconazole, and amphotericin B and 8 to 10 mice per miltefosine dose).
In the disseminated cryptococcosis model, miltefosine therapy was continued through day 7 while amphotericin B was administered for two doses. The lungs and brains were collected on day 8 for fungal burden quantification (n = 10 mice per group).