Interactions of liposomal amphotericin B with extracellular and intracellular Candida albicans.
The in-vitro activities of liposomal amphotericin B (AmBisome) and amphotericin B-desoxycholate (AmB-DOC) against extracellular Candida albicans during 6 h of incubation in the presence of human serum were determined. With AmB-DOC inhibition of germ tube formation and effective killing were observed at AmB-concentrations of 0.8 and 3.2 mg/L, respectively. With AmBisome for both parameters tested, 32-fold increased AmB concentrations were needed. Preincubation of AmBisome in human serum for 6 h did not influence the rate of killing of C. albicans. Antifungal activity against intracellular C. albicans was assessed at 4 h and 24 h after incubation of C. albicans-infected monolayers of mouse peritoneal macrophages with antifungal agent. In the absence of antifungal agent C. albicans grows intracellularly by formation of germ tubes, and within 24 h mycelium is formed. Antifungal activity was evaluated in terms of both stabilization of the state of infection, as well as eradication of C. albicans from infected macrophages. For AmBisome stabilization only was observed at a concentration of 102 mg/L after 24 h of incubation. For AmB-DOC stabilization and eradication were observed only after 24 h of incubation at 0.8 and 1.6 mg/L, respectively. After previous exposure of macrophages to AmBisome for 6 h before infection, increased antifungal activity of AmBisome was observed: stabilization was observed at 4 h of incubation at 102 mg/L; at 24 h of incubation stabilization and eradication were observed at 25.6 mg/L and 102 mg/L, respectively. Prolongation of the exposure time before C. albicans infection from 6 h up to 24 h resulted in a further increase in antifungal activity of AmBisome. Localization studies of AmBisome and C. albicans in macrophages were performed using fluorescent-labelled C. albicans and fluorescent-labelled AmBisome. The presence of AmBisome within a macrophage was found not to influence uptake of C. albicans by the same macrophage, or vice versa.
van Etten
E W
EW
Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, Netherlands.
Chander
H R
HR
Snijders
S V
SV
Bakker-Woudenberg
I A
IA
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D004337:Drug Carriers; D004338:Drug Combinations; D008081:Liposomes; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination