Efficacy of amphotericin B and azoles alone and in combination against disseminated trichosporonosis in neutropenic mice.
The activities of amphotericin B, miconazole, fluconazole, and itraconazole against Trichosporon beigelii were assessed in a mouse model of disseminated infection. Cyclophosphamide plus prednisolone-immunosuppressed ICR mice, intravenously challenged with a lethal inoculum of (6 x 10(6) CFU/ mouse), were assigned to receive 7 days of therapy with amphotericin B (0.5 or 2 mg/kg/day), miconazole (10 or 40 mg/kg/day), fluconazole (10 or 40 mg/kg/day), or itraconazole (10 and 40 mg/kg/day). The efficacy of a combination of amphotericin B (1 mg/kg/day) with that fluconazole (10 mg/kg/ day) or itraconazole (20 mg/kg/day) with that of each agent alone was also compared. Both amphotericin B and azoles improved survival and reduced the fungal counts in kidneys of infected mice in a dose-dependent pattern. In general, fluconazole was superior to amphotericin B and the other azoles, whereas the latter two drugs were as effective as amphotericin B. The activity of amphotericin B combined with fluconazole appeared to be superior to that of each agent alone, especially in reducing the organ fungal burden. The other combination (amphotericin B plus itraconazole) had a weaker effect, but no antagonism was observed. In conclusion, azoles may be an alternative to amphotericin B for the treatment of T. beigelii infection. Furthermore, their combination with amphotericin B may improve the poor outcome seen in profoundly neutropenic patients with disseminated trichosporonosis.
Kamberi
P
P
Second Department of Internal Medicine, Oita Medical University, Japan.
Atsuro
H
H
Takayoshi
T
T
Masaru
N
N
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000494:pharmacology; D017964:Itraconazole / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008825:Miconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000097:blood* / Q000188:drug therapy*; D009503:Neutropenia / Q000382:microbiology*; D014250:Trichosporon / Q000187:drug effects*
D000935:Antifungal Agents; D001393:Azoles; D017964:Itraconazole; D008825:Miconazole; D000666:Amphotericin B; D015725:Fluconazole