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Efficacy of amphotericin B and azoles alone and in combination against disseminated trichosporonosis in neutropenic mice.

Abstract
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.
AuthorsP Kamberi, H Atsuro, T Takayoshi, N Masaru
JournalChemotherapy (Chemotherapy) 1998 Jan-Feb Vol. 44 Issue 1 Pg. 55-62 ISSN: 0009-3157 [Print] Switzerland
PMID9444410 (Publication Type: Journal Article)
Chemical References
  • Antifungal Agents
  • Azoles
  • Itraconazole
  • Miconazole
  • Amphotericin B
  • Fluconazole
Topics
  • Amphotericin B (pharmacology)
  • Animals
  • Antifungal Agents (pharmacology)
  • Azoles (pharmacology)
  • Drug Therapy, Combination
  • Fluconazole (pharmacology)
  • Itraconazole (pharmacology)
  • Male
  • Mice
  • Mice, Inbred ICR
  • Miconazole (pharmacology)
  • Microbial Sensitivity Tests
  • Mycoses (blood, drug therapy)
  • Neutropenia (microbiology)
  • Trichosporon (drug effects)

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