Effects of amphotericin B incorporated into liposomes and in lipid suspensions in the treatment of murine candidiasis.
The effects of similar amounts of amphotericin B (CAS 1397-89-3, AmB) in different preparations either as conventional amphotericin B (des-AmB), or liposomal AmB (lipos-AmB), or des-AmB dissolved in a lipid emulsion (lipid-AmB) on Candida albicans and other Candida species were compared in several in vitro and in vivo models. The minimal inhibitory concentration (MIC) of des-AmB was equal to the MIC of lipid-AmB when determined after 24 h. In contrast, the MIC of lipos-AmB was 4-8 times the MIC of des-AmB. When tested at 4 times the MIC of the respective preparations suspension of lipid-AmB led to a reduced ability to kill the fungi whereas des-AmB reduced the inoculum by 99% within 6 h. Four times the MIC of lipos-AmB failed completely to kill the fungi in the same time, but was only fungistatic. At 24 h all preparations had killed the yeasts at concentrations 4 times the MIC. In contrast to the in vitro data, lipos-AmB was more active in the treatment of murine candidiasis than lipid-AmB and des-AmB. Lipos-AmB but not lipid-AmB or des-AmB was able to significantly reduce the amount of Candida albicans in the liver when given in the same dosage. Concomitantly, AmB measured by HPLC was highly concentrated in the livers of the mice treated with lipos-AmB. It is concluded that even when given in the same dosage as des-AmB and lipid-AmB, lipos-AmB is more effective in the treatment of murine candidiasis, although it is less effective in vitro. Lipid-AmB is no alternative to lipos-AmB in this model of systemic infection of mice with Candida albicans.
Kretschmar
M
M
Institute of Medical Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
Nichterlein
T
T
Hannak
D
D
Hof
H
H
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D005260:Female; D007378:Interleukins / Q000378:metabolism; D008055:Lipids; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D013535:Suspensions; D014018:Tissue Distribution
D000935:Antifungal Agents; D007378:Interleukins; D008055:Lipids; D008081:Liposomes; D013535:Suspensions; D000666:Amphotericin B