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Cryptococcus neoformans

  • The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection
    Experimental Therapeutics
    The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection

    Invasive fungal diseases represent an unmet clinical need that could benefit from novel immunotherapeutic approaches. Host pattern recognition receptors (e.g., Toll-like receptors, C-type lectins, or scavenger receptors) that sense conserved fungal cell wall constituents may provide suitable immunotherapeutic antifungal agents. Thus, we explored the therapeutic potential of the lymphocyte class I scavenger receptor CD5, a nonredundant...

    María Velasco-de Andrés, Cristina Català, Sergi Casadó-Llombart, Mario Martínez-Florensa, Inês Simões, Joaquín García-Luna, Gustavo Mourglia-Ettlin, Óscar Zaragoza, Esther Carreras, Francisco Lozano
  • Comparison of MIC Test Strip and Sensititre YeastOne with the CLSI and EUCAST Broth Microdilution Reference Methods for <em>In Vitro</em> Antifungal Susceptibility Testing of <span class="named-content genus-species" id="named-content-1">Cryptococcus neoformans</span>
    Susceptibility
    Comparison of MIC Test Strip and Sensititre YeastOne with the CLSI and EUCAST Broth Microdilution Reference Methods for In Vitro Antifungal Susceptibility Testing of Cryptococcus neoformans

    We compared MIC test strip (MTS) and Sensititre YeastOne (SYO) methods with EUCAST and CLSI methods for amphotericin B, 5-fluocytosine, fluconazole, voriconazole, and isavuconazole against 106 Cryptococcus neoformans isolates. The overall essential agreement between the EUCAST and CLSI methods was >72% and >94% at ±1 and ±2 dilutions, respectively. The essential...

    Fatima Zohra Delma, Abdullah M. S. Al-Hatmi, Jochem B. Buil, Hein van der Lee, Marlou Tehupeiory-Kooreman, G. Sybren de Hoog, Joseph Meletiadis, Paul E. Verweij
  • Identification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against <span class="named-content genus-species" id="named-content-1">Cryptococcus neoformans</span> and <em>Candida</em> spp.
    Experimental Therapeutics
    Identification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against Cryptococcus neoformans and Candida spp.

    Amphotericin B (AmB) is the antifungal with the strongest fungicidal activity, but its use has several limitations, mainly associated with its toxicity. Although some lipidic and liposomal formulations that present reduced toxicity are available, their price limits their application in developing countries. Flucytosine (5FC) has shown synergistic effect with AmB for treatment of some fungal infections, such as cryptococcosis, but again...

    Suélen Andreia Rossi, Haroldo Cesar de Oliveira, Daniel Agreda-Mellon, José Lucio, Maria José Soares Mendes-Giannini, Jesús Pablo García-Cambero, Oscar Zaragoza
  • Derivatives of the Antimalarial Drug Mefloquine Are Broad-Spectrum Antifungal Molecules with Activity against Drug-Resistant Clinical Isolates
    Experimental Therapeutics
    Derivatives of the Antimalarial Drug Mefloquine Are Broad-Spectrum Antifungal Molecules with Activity against Drug-Resistant Clinical Isolates

    The antifungal pharmacopeia is critically small, particularly in light of the recent emergence of multidrug-resistant pathogens, such as Candida auris. Here, we report that derivatives of the antimalarial drug mefloquine have broad-spectrum antifungal activity against pathogenic yeasts and molds.

    Marhiah C. Montoya, Sarah Beattie, Kathryn M. Alden, Damian J. Krysan
  • New Triazole NT-a9 Has Potent Antifungal Efficacy against <span class="named-content genus-species" id="named-content-1">Cryptococcus neoformans</span> <em>In Vitro</em> and <em>In Vivo</em>
    Experimental Therapeutics
    New Triazole NT-a9 Has Potent Antifungal Efficacy against Cryptococcus neoformans In Vitro and In Vivo

    In the past decades, the incidence of cryptococcosis has increased dramatically, which poses a new threat to human health. However, only a few drugs are available for the treatment of cryptococcosis. Here, we described a leading compound, NT-a9, an analogue of isavuconazole, that showed strong antifungal activities in vitro and in vivo.

    Ren-Yi Lu, Ting-Jun-Hong Ni, Jing Wu, Lan Yan, Quan-Zhen Lv, Li-Ping Li, Da-Zhi Zhang, Yuan-Ying Jiang
  • Open Access
    Pharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal Meningoencephalitis
    Pharmacology
    Pharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal Meningoencephalitis

    Cryptococcus spp., important fungal pathogens, are the leading cause of fungus-related mortality in human immunodeficiency virus-infected patients, and new therapeutic options are desperately needed. Isavuconazonium sulfate, a newer triazole antifungal agent, was studied to characterize the exposure-response relationship in a rabbit model of cryptococcal meningoencephalitis. Rabbits treated with isavuconazonium sulfate were...

    Laura L. Kovanda, Charles Giamberardino, Laura McEntee, Dena L. Toffaletti, Kelly S. Franke, Andrew Bartuska, Gordon Smilnak, George C. de Castro, Katelyn Ripple, William W. Hope, John R. Perfect
  • <em>In Vivo</em> Efficacy of VT-1129 against Experimental Cryptococcal Meningitis with the Use of a Loading Dose-Maintenance Dose Administration Strategy
    Experimental Therapeutics
    In Vivo Efficacy of VT-1129 against Experimental Cryptococcal Meningitis with the Use of a Loading Dose-Maintenance Dose Administration Strategy

    VT-1129 is a novel fungal enzyme-specific Cyp51 inhibitor with potent cryptococcal activity. Because of its long half-life (>6 days in mice) and our desire to quickly reach potent efficacy, we evaluated a VT-1129 loading dose-maintenance dose strategy against cryptococcal meningitis.

    Nathan P. Wiederhold, Xin Xu, Amy Wang, Laura K. Najvar, Edward P. Garvey, Elizabeth A. Ottinger, Asaf Alimardanov, Jim Cradock, Mark Behnke, William J. Hoekstra, Stephen R. Brand, Robert J. Schotzinger, Rosie Jaramillo, Marcos Olivo, William R. Kirkpatrick, Thomas F. Patterson
  • Experimental Therapeutics
    The Fungal Cyp51 Inhibitor VT-1129 Is Efficacious in an Experimental Model of Cryptococcal Meningitis

    Cryptococcal meningitis is a significant cause of morbidity and mortality in immunocompromised patients. VT-1129 is a novel fungus-specific Cyp51 inhibitor with potent in vitro activity against Cryptococcus species.

    Nathan P. Wiederhold, Laura K. Najvar, Edward P. Garvey, Stephen R. Brand, Xin Xu, Elizabeth A. Ottinger, Asaf Alimardanov, Jim Cradock, Mark Behnke, William J. Hoekstra, Robert J. Schotzinger, Rosie Jaramillo, Marcos Olivo, William R. Kirkpatrick, Thomas F. Patterson
  • Open Access
    Experimental Therapeutics
    Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids
    Cristina Lazzarini, Krupanandan Haranahalli, Robert Rieger, Hari Krishna Ananthula, Pankaj B. Desai, Alan Ashbaugh, Michael J. Linke, Melanie T. Cushion, Bela Ruzsicska, John Haley, Iwao Ojima, Maurizio Del Poeta
  • Open Access
    Pharmacology
    Repurposing and Reformulation of the Antiparasitic Agent Flubendazole for Treatment of Cryptococcal Meningoencephalitis, a Neglected Fungal Disease
    Gemma L. Nixon, Laura McEntee, Adam Johnson, Nicola Farrington, Sarah Whalley, Joanne Livermore, Cristien Natal, Gina Washbourn, Jaclyn Bibby, Neil Berry, Jodi Lestner, Megan Truong, Andrew Owen, David Lalloo, Ian Charles, William Hope

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