Combination efficacy of voriconazole and amphotericin B in the experimental disease in immunodeficient mice caused by fluconazole-resistant Cryptococcus neoformans.
The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 × 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.
Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Professor Lineu Prestes 1374, 2º andar, sala 247, São Paulo (USP), 05508-900, Brazil. eriques@usp.br
Eriques Gonçalves
EG
Silva
Claudete Rodrigues
CR
Paula
Amanda Latercia Tranches
AL
Dias
Marilene Rodrigues
MR
Chang
Luciana da Silva
Lda S
Ruiz
Valderez
V
Gambale
Renato Araujo
RA
Prates
Martha Simões
MS
Ribeiro
D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001921:Brain / Q000382:microbiology; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000188:drug therapy*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D004359:Drug Therapy, Combination / Q000379:methods; D015725:Fluconazole / Q000494:pharmacology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011743:Pyrimidines / Q000008:administration & dosage*; D012376:Rodent Diseases / Q000188:drug therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D065819:Voriconazole; D015003:Yeasts
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D015725:Fluconazole; D065819:Voriconazole