title: In vivo activity of micafungin in a persistently neutropenic murine model of disseminated infection caused by Candida tropicalis.
abstract: Micafungin is a new echinocandin with broad-spectrum in vitro and in vivo antifungal activity against both Aspergillus and Candida species. We compared the activity of micafungin with that of amphotericin B and fluconazole in a persistently immunocompromised murine model of disseminated candidiasis against a strain of Candida tropicalis that was resistant to amphotericin B and fluconazole in vitro. Mice were rendered persistently neutropenic with multiple doses of cyclophosphamide and infected intravenously with C. tropicalis. Mice were treated with either intraperitoneal amphotericin B (0.5-5 mg/kg per dose), oral fluconazole (50 mg/kg twice a day), intravenous micafungin (1-10 mg/kg per dose) or solvent control for 7 days. Mice were killed at 11 days post-infection and kidneys, lungs, brain and liver removed for quantitative culture. Overall mortality in the model was low, with rates varying between 10% and 25% in treatment groups. Micafungin at doses between 2 and 10 mg/kg were the only regimes able to reduce cfu below the level of detection of tissues infected with C. tropicalis. Micafungin was well tolerated by the mice and was much more effective than amphotericin B or fluconazole against an amphotericin B- and fluconazole-resistant C. tropicalis.
authors.affiliation: School of Medicine, University of Manchester, UK. pwarn@fs1.ho.man.ac.uk
authors.forename: Peter A
authors.initials: PA
authors.lastname: Warn
authors.forename: Andrew
authors.initials: A
authors.lastname: Sharp
authors.forename: Graham
authors.initials: G
authors.lastname: Morrissey
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D041022:Candida tropicalis / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D004195:Disease Models, Animal; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D000077551:Micafungin; D051379:Mice; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077551:Micafungin