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Antimicrobial Agents and Chemotherapy, September 2000, p. 2327-2332, Vol. 44, No. 9
California State Polytechnic University,
Pomona, California 91768,1 and
NeXstar Pharmaceuticals, Inc.,§ San Dimas,
California 917732
Received 1 March 2000/Returned for modification 18 April
2000/Accepted 31 May 2000
AmBisome is a liposomal formulation of amphotericin B that has
broad-spectrum antifungal activity and greatly reduced toxicity compared to the parent drug. In this study, amphotericin B deoxycholate (Fungizone) (1 mg/kg) and AmBisome (1 to 20 mg/kg) were tested as
single-dose prophylactic agents in both immunocompetent and immunosuppressed C57BL/6 mice challenged with either Candida
albicans or Histoplasma capsulatum. Prophylactic
efficacy was based on survival and fungal burden in the target organ
(kidneys or spleen). At 9 to 10 days after histoplasma challenge, 80 to
90% of both immunocompetent and immunosuppressed mice in the control
and Fungizone groups had died. All AmBisome-treated mice survived,
although in the AmBisome groups given 1 mg/kg, the mice became moribund by day 10 to 12. No spleen CFU were detected in the
histoplasma-challenged mice given 10 or 20 mg of AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal growth and/or death had
occurred in all immunosuppressed mice except for four mice receiving 20 mg of AmBisome per kg. There were still no detectable fungi in the
spleens of immunocompetent mice given 10 or 20 mg of AmBisome per kg.
In the C. albicans experiment at 7 days postchallenge, all
animals in both untreated and treated groups were alive with culture-positive kidneys. The kidney fungal burdens in AmBisome groups
given 5 to 20 mg/kg were at least 1 log unit lower than those in the
Fungizone group and significantly lower than those in the untreated
control group (P < 0.05). There was a trend toward decreasing fungal growth in the kidneys as the dose of AmBisome was
increased. In conclusion, these results show that a single high dose of
AmBisome (5 to 20 mg/kg) had prophylactic efficacy in immunocompetent
and immunosuppressed murine H. capsulatum and C. albicans models.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Single-Dose AmBisome (Liposomal Amphotericin B) as
Prophylaxis for Murine Systemic Candidiasis and
Histoplasmosis
*
Corresponding author. Mailing address: Dept. of
Biological Sciences, California State Polytechnic University, Pomona,
CA 91768. Phone: (909) 869-4047. Fax: (909) 869-4078. E-mail:
jpadler{at}csupomona.edu.
Present address: Sanitation Districts of Los Angeles County,
Whittier, CA 90601.
Present address: 11 N. Altura Rd., Arcadia, CA 91007.
§
Merged with Gilead Sciences, Inc., Foster City, CA 94404, in 1999.
Antimicrobial Agents and Chemotherapy, September 2000, p. 2327-2332, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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