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Combination Efficacy of Voriconazole and Amphotericin B in the Experimental Disease in Immunodeficient Mice Caused by Fluconazole-resistant Cryptococcus neoformans

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Abstract

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 × 105 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.

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Acknowledgments

The authors are grateful to Pfizer for providing pure voriconazole, to Mr. Carlos Augusto da Silva, the Animal Center Technician, for his valuable assistance and FAPESP and CNPq/for financial support.

Conflict of interest

No conflict of interest with the present study.

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Authors and Affiliations

  1. Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), Av. Professor Lineu Prestes 1374, 2º andar, sala 247, São Paulo (USP), 05508-900, Brazil

    Eriques Gonçalves Silva, Claudete Rodrigues Paula, Luciana da Silva Ruiz & Valderez Gambale

  2. Universidade Federal de Alfenas-UNIFAL, Alfenas, Minas Gerais, Brazil

    Amanda Latercia Tranches Dias

  3. Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil

    Marilene Rodrigues Chang

  4. IPEN/CNEN, Centro de Lasers e Aplicações (CLA)-Instituto de Pesquisas Energéticas e Nucleares, São Paulo, Brazil

    Renato Araujo Prates & Martha Simões Ribeiro

Authors
  1. Eriques Gonçalves Silva
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  2. Claudete Rodrigues Paula
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  3. Amanda Latercia Tranches Dias
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  4. Marilene Rodrigues Chang
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  5. Luciana da Silva Ruiz
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  6. Valderez Gambale
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  7. Renato Araujo Prates
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  8. Martha Simões Ribeiro
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Correspondence to Eriques Gonçalves Silva.

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Silva, E.G., Paula, C.R., Dias, A.L.T. et al. Combination Efficacy of Voriconazole and Amphotericin B in the Experimental Disease in Immunodeficient Mice Caused by Fluconazole-resistant Cryptococcus neoformans . Mycopathologia 171, 261–266 (2011). https://doi.org/10.1007/s11046-010-9375-5

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  • DOI: https://doi.org/10.1007/s11046-010-9375-5

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