Table 1

Fungal burden in the brains or lungs of mice with cryptococcal meningoencephalitis or disseminated cryptococcosis following intracranial or intravenous inoculation with C. neoformans USC1597

Inoculation method and tissueC. neoformans USC1597 fungal burden (log10 CFU/gram) by treatmenta
ControlMTF (mg/kg)FLCAMBMTF (45 mg/kg) + FLCMTF (45 mg/kg) + AMB
5101545
Intracranialb
    Brain6.04 ± 0.515.57 ± 0.355.98 ± 0.515.61 ± 0.546.03 ± 0.422.64 ± 1.05*2.20 ± 0.92*3.32 ± 0.90*2.83 ± 1.32*
Intravenousc
    Lung7.22 ± 0.627.46 ± 0.285.77 ± 1.99**5.67 ± 1.61**
    Brain6.23 ± 0.236.34 ± 0.154.35 ± 1.20*4.04 ± 1.02*
  • a 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).

  • b 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).

  • c 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).