Alternative dosing regimens of liposomal amphotericin B (AmBisome) effective in treating murine systemic candidiasis.
OBJECTIVE
This study was done to determine whether high dose AmBisome (4-20 mg/kg), given intermittently, could reduce the frequency of dosing needed to treat murine systemic candidiasis when compared with conventional daily treatment.


METHODS
Mice were immunosuppressed with cyclophosphamide every 3 days, beginning day -3 before challenge with log(10) 5.0 cfu Candida albicans. Treatment was begun 48-72 h post-challenge with daily or intermittent dose regimens of AmBisome, followed by determination of kidney cfu for up to 1 month post-treatment.


RESULTS
A single AmBisome dose of 4 mg/kg was as effective as four daily, 1 mg/kg treatments. A total of 8 mg/kg, given as 4 mg/kg on days 2 and 4, or as 5 mg/kg on day 2 followed by 1 mg/kg on days 3, 4, and 5, also produced comparable efficacy. While 20 mg/kg given day 2, 4 and 6 post-challenge as a 1 week loading dose, followed by one 10 mg/kg treatment on day 13, decreased the fungal burden by up to 5 logs compared with controls (log(10) 2.3 cfu/g and log(10) 7.5 cfu/g, respectively), 20 mg/kg given Monday, Wednesday and Friday for 5 weeks, reduced the fungal burden to undetectable levels (i.e. log(10) 1.0 cfu).


CONCLUSIONS
Significant reduction or clearance of kidney cfu, following intermittent, high dose AmBisome treatment, indicated that non-daily dosing regimens could be successfully used instead of conventional daily dosing to treat established C. albicans infection in immunosuppressed mice.
Adler-Moore
Jill P
JP
Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768, USA. jpadler@csupomona.edu
Olson
Jon A
JA
Proffitt
Richard T
RT
D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D016867:Immunocompromised Host; D007668:Kidney / Q000382:microbiology; D008081:Liposomes / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome
D000935:Antifungal Agents; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B