Combined antifungal therapy in a murine model of disseminated infection by Cladophialophora bantiana.
We tested ten day courses of amphotericin B (AMB), micafungin (MFG), voriconazole (VRC), flucytosine (5FC) and posaconazole (PSC) alone and in double or triple combinations in the treatment of disseminated infections caused by Cladophialophora bantiana in a murine model. Animals were monitored for survival for 40 days. We found that PSC at 100 mg/kg or 5FC at 180 mg/kg prolonged survival over controls. The combinations PSC+MFG and PSC+5FC improved survival compared to MFG and 5FC alone, but were not superior to PSC alone. The triple combination of PSC+MFG+5FC improved the survival with respect to both the control group and the component monotherapies, but all the animals died during the experiment. When treatment with this triple therapy was extended up to 30 days, half of the animals survived for at least 10 months. Combination therapy with the three drugs (PSC, MFG and 5FC) appears to be a promising option for the treatment of C. bantiana infections.
Mariné
Marçal
M
Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Spain.
Pastor
F Javier
FJ
Guarro
Josep
J
D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001203:Ascomycota / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage / Q000627:therapeutic use; D005437:Flucytosine / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D055666:Lipopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D051379:Mice; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; D000666:Amphotericin B; D005437:Flucytosine; D000077551:Micafungin