Comparative effects of cilofungin and amphotericin B on experimental murine candidiasis.
The effectiveness of cilofungin (LY121019, referred to hereafter as LY), a lipopeptide, was studied in a murine candidiasis model. CD-1 mice (5 weeks old) were injected intravenously with 3 x 10(5) Candida albicans yeast cells. Intraperitoneal LY or amphotericin B (AmB) therapy was begun 4 days after infection and was continued daily for 2 weeks. LY and AmB were compared at 62.5, 6.25, and 0.625 mg/kg per day, with the LY dose split into two treatments per day. Mice were observed for 30 days postinfection, and survivors were necropsied. AmB at 62.5 mg/kg per day was lethal in the absence of infection. Cumulative mortality for infected controls was 94% (17 of 18). Survival of mice treated with the control diluent for LY was the same as survival with no treatment. Survival after 0.625 mg of LY per kg per day was the same as that of the controls, and 6.25 or 62.5 mg of LY per kg per day was significantly superior. AmB treatment at 0.625 or 6.25 mg/kg per day was protective and superior to the same LY doses. Atrophied kidneys were common in AmB-treated mice, and mice treated with 6.25 mg of AmB per kg per day appeared ill during therapy. The number of CFU recovered from kidneys and spleens of surviving mice reflected the same relationships between drugs and doses as those described for mortality. C. albicans was not cleared from the kidneys of mice in any group, and only in the 6.25-mg/kg-per-day AmB treatment group was not detectable C. albicans found in the spleens. These data indicate that LY or AmB suppresses candida infection but neither is curative in this model.
Department of Medicine, Santa Clara Valley Medical Center, San Jose, California.
C J
CJ
Morrison
D A
DA
Stevens
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D054714:Echinocandins; D006207:Half-Life; D007674:Kidney Diseases / Q000473:pathology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D010456:Peptides, Cyclic; D013154:Spleen / Q000382:microbiology
D000935:Antifungal Agents; D054714:Echinocandins; D010455:Peptides; D010456:Peptides, Cyclic; D000666:Amphotericin B; C042101:cilofungin