Combined antifungal therapy in a murine infection by Candida glabrata.
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.
Mariné
Marçal
M
Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201, Reus, Spain.
Serena
Carolina
C
Pastor
F Javier
FJ
Guarro
Josep
J
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
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine; D000077551:Micafungin