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Aspergillus

  • Open Access
    Antifungal Effect of All-<em>trans</em> Retinoic Acid against <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> <em>In Vitro</em> and in a Pulmonary Aspergillosis <em>In Vivo</em> Model
    Experimental Therapeutics
    Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo Model

    Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro.

    Elena Campione, Roberta Gaziano, Elena Doldo, Daniele Marino, Mattia Falconi, Federico Iacovelli, Daniela Tagliaferri, Lucrezia Pacello, Luca Bianchi, Caterina Lanna, Luigi Aurisicchio, Federica Centofanti, Paolo Di Francesco, Ilaria Del Principe, Francesca Del Bufalo, Franco Locatelli, Enrico Salvatore Pistoia, Emanuele Marra, Augusto Orlandi
  • Open Access
    Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and <em>Pneumocystis</em> Pneumonia
    Experimental Therapeutics
    Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis Pneumonia

    Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive...

    Lynn Miesel, Melanie T. Cushion, Alan Ashbaugh, Santiago R. Lopez, Voon Ong
  • Olorofim Susceptibility Testing of 1,423 Danish Mold Isolates Obtained in 2018-2019 Confirms Uniform and Broad-Spectrum Activity
    Susceptibility
    Olorofim Susceptibility Testing of 1,423 Danish Mold Isolates Obtained in 2018-2019 Confirms Uniform and Broad-Spectrum Activity

    Olorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus. Here, we explored the MIC variability in more detail and prospectively investigated the susceptibility of contemporary clinical mold isolates...

    Karen Marie Thyssen Astvad, Karin Meinike Jørgensen, Rasmus Krøger Hare, Raluca Datcu, Maiken Cavling Arendrup
  • Preclinical Evaluation of Acylhydrazone SB-AF-1002 as a Novel Broad-Spectrum Antifungal Agent
    Experimental Therapeutics
    Preclinical Evaluation of Acylhydrazone SB-AF-1002 as a Novel Broad-Spectrum Antifungal Agent

    The incidence of invasive fungal infections is rising due to the increase in susceptible populations. Current clinically available drugs have therapeutic limitations due to toxicity, a narrow spectrum of activity, and, more importantly, the consistent rise of fungal species that are intrinsically resistant or that develop resistance due to prolonged therapy. Thus, there is an urgent need for new broad-spectrum antifungal agents with low...

    Cristina Lazzarini, Krupanandan Haranahalli, J. Brian McCarthy, John Mallamo, Iwao Ojima, Maurizio Del Poeta
  • A Novel Combination of <em>CYP51A</em> Mutations Confers Pan-Azole Resistance in <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span>
    Editor's Pick Mechanisms of Resistance
    A Novel Combination of CYP51A Mutations Confers Pan-Azole Resistance in Aspergillus fumigatus

    The treatment of invasive and chronic aspergillosis involves triazole drugs. Its intensive use has resulted in the selection of resistant isolates, and at present, azole resistance in Aspergillus fumigatus is considered an emerging threat to public health worldwide. The aim of this work is to uncover the molecular mechanism implicated in the azole resistance phenotype...

    Daiana Macedo, Tomás Brito Devoto, Santiago Pola, Jorge L. Finquelievich, María L. Cuestas, Guillermo Garcia-Effron
  • <em>In Vitro</em> Activity of Manogepix (APX001A) and Comparators against Contemporary Molds: MEC Comparison and Preliminary Experience with Colorimetric MIC Determination
    Editor's Pick Susceptibility
    In Vitro Activity of Manogepix (APX001A) and Comparators against Contemporary Molds: MEC Comparison and Preliminary Experience with Colorimetric MIC Determination

    Manogepix (APX001A) is the active moiety of the drug candidate fosmanogepix (APX001), currently in clinical development for the treatment of invasive fungal infections. We compared manogepix EUCAST minimum effective concentrations (MECs) to MICs of five comparators and CLSI MECs and MICs by a colorimetric method against contemporary molds. EUCAST susceptibility testing was performed for 161 isolates. Interlaboratory and intermethod...

    Karin Meinike Jørgensen, Karen M. T. Astvad, Maiken Cavling Arendrup
  • <em>In Vitro</em> and <em>In Vivo</em> Study on the Synergistic Effect of Minocycline and Azoles against Pathogenic Fungi
    Susceptibility
    In Vitro and In Vivo Study on the Synergistic Effect of Minocycline and Azoles against Pathogenic Fungi

    In vitro and in vivo interactions of minocycline and azoles, including itraconazole, voriconazole, and posaconazole, against filamentous pathogenic fungi were investigated. A total of 56 clinical isolates were studied in vitro via broth microdilution checkerboard technique, including 20 strains of Aspergillus fumigatus, 7 strains of...

    Lujuan Gao, Yi Sun, Mingzhu Yuan, Ming Li, Tongxiang Zeng
  • 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
  • Open Access
    Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis
    Experimental Therapeutics
    Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis

    Galactomannan (GM) detection in biological samples has been shown to predict therapeutic response by azoles and polyenes. In a murine invasive pulmonary aspergillosis model, fosmanogepix or posaconazole treatment resulted in an ∼6- to 7-log reduction in conidial equivalents (CE)/g lung tissue after 96 h versus placebo.

    Teclegiorgis Gebremariam, Sondus Alkhazraji, Yiyou Gu, Shakti Singh, Abdullah Alqarihi, Karen Joy Shaw, Ashraf S. Ibrahim
  • New Antifungal Susceptibility Test Based on Chitin Detection by Image Cytometry
    Susceptibility
    New Antifungal Susceptibility Test Based on Chitin Detection by Image Cytometry

    The antifungal susceptibility tests used in clinical laboratories have several limitations. We developed a new test, SensiFONG, based on the detection of chitin levels after exposure to antifungal drugs. The optimal culture conditions were 30°C for 6 h for yeast strains and 26°C for 16 h for molds. The strains were exposed to a range of echinocandin or azole concentrations. Chitin was stained with calcofluor white.

    Yan Wang, Arisandy N. Andriampamonjy, Sebastien Bailly, Cécile Garnaud, Danièle Maubon, Muriel Cornet, Delphine Aldebert

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