title: Combined antifungal therapy in a murine infection by Candida glabrata.
abstract: OBJECTIVE
  To develop proper treatments for patients who do not respond to current antifungal treatments, we tested new combinations of antifungal drugs for treating disseminated infections by Candida glabrata in a murine model.
  
  
  METHODS
  Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous 5-fluorouracil administration. The animals were infected intravenously with 2 x 10(8) cfu of C. glabrata. The efficacies of micafungin combined with amphotericin B, fluconazole or flucytosine, and of amphotericin B combined with fluconazole were evaluated by survival and tissue burden reduction.
  
  
  CONCLUSIONS
  Micafungin plus amphotericin B was the most effective combination at reducing tissue burden. Micafungin at 10 mg/kg combined with amphotericin B at 0.75, 1.5 or 3 mg/kg prolonged survival with respect to the monotherapies, but only the second combination showed a synergistic effect in reducing fungal load in spleen and kidney. Amphotericin B at 1.5 mg/kg combined with micafungin at 5, 10 or 20 mg/kg reduced tissue burden with respect to the monotherapies, but the effects of the three combinations were very similar. These results suggest that amphotericin B in combination with micafungin is promising for the treatment of disseminated C. glabrata infections.
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Marçal
authors.initials: M
authors.lastname: Mariné
authors.forename: Carolina
authors.initials: C
authors.lastname: Serena
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Pastor
authors.forename: Josep
authors.initials: J
authors.lastname: Guarro
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D041221:Candida glabrata / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D054714:Echinocandins; D015725:Fluconazole / Q000627:therapeutic use; D005437:Flucytosine / Q000627:therapeutic use; D016867:Immunocompromised Host; D007668:Kidney / Q000382:microbiology; D055666:Lipopeptides; D008074:Lipoproteins / Q000627:therapeutic use; D000077551:Micafungin; D051379:Mice; D010456:Peptides, Cyclic / Q000627:therapeutic use; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine; D000077551:Micafungin