[In vivo activity of liposomal amphotericin B against Exophiala dermatitidis in a murine lethal infection model].
This study evaluated the in vivo activity of liposomal amphotericin B (L-AMB) and deoxycholate amphotericin B (D-AMB) in a murine model of disseminated infection caused by Exophiala dermatitidis. Cyclophosphamide-treated neutropenic ddY mice were inoculated intravenously with conidial suspensions of E. dermatitidis IFM 4827 or IFM 53409. The maximum tolerated doses of L-AMB and D-AMB were set at 10 mg/kg and 1 mg/kg, respectively. Four hours after infection, a single dose of L-AMB (0.3 to 10 mg/kg) or D-AMB (0.1 to 1 mg/kg) was administered intravenously. The efficacy of the antifungal treatment was assessed by the survival time over two weeks and the tissue fungal burdens 4 days after infection. L-AMB at a dose of > or =1 mg/kg significantly prolonged the survival time of mice infected with either strain compared with that of the control group. Percent survivals in the 10 mg/kg L-AMB-treated group (100% and 75%) were higher than those in the 1 mg/kg D-AMB-treated group (20% and 37.5%) in the IFM 4827 and IFM 53409 models, respectively. In the IFM 4827 model, 10 mg/kg L-AMB exhibited greater efficacy than 1 mg/kg D-AMB in terms of reducing the tissue fungal burdens (blood, lung, liver, spleen, and kidneys). These findings suggest that L-AMB was effective in the treatment of experimental disseminated E. dermatitidis infection, and the efficacy of L-AMB was superior to that of D-AMB.
Kashimoto
Shigeki
S
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd.
Takemoto
Koji
K
Yamamoto
Yutaka
Y
Kanazawa
Katsunori
K
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000008:administration & dosage; D003872:Dermatitis / Q000188:drug therapy*; D003881:Dermatomycoses / Q000188:drug therapy*; D005093:Exophiala / Q000187:drug effects*; D008297:Male; D051379:Mice
D000935:Antifungal Agents; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B