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echinocandins

  • Manogepix (APX001A) <em>In Vitro</em> Activity against <span class="named-content genus-species" id="named-content-1">Candida auris</span>: Head-to-Head Comparison of EUCAST and CLSI MICs
    Susceptibility
    Manogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICs

    Fosmanogepix is a novel prodrug in a new class of antifungal agents. Manogepix is the active moiety. We evaluated the CLSI and EUCAST MICs of manogepix and eight comparators against Candida auris. CLSI M27-A3 susceptibility testing of manogepix was performed for 122 C. auris isolates and compared to...

    Maiken Cavling Arendrup, Anuradha Chowdhary, Karin Meinike Jørgensen, Joseph Meletiadis
  • Unexpected Cell Wall Alteration-Mediated Bactericidal Activity of the Antifungal Caspofungin against Vancomycin-Resistant <span class="named-content genus-species" id="named-content-1">Enterococcus faecium</span>
    Editor's Pick Mechanisms of Action: Physiological Effects
    Unexpected Cell Wall Alteration-Mediated Bactericidal Activity of the Antifungal Caspofungin against Vancomycin-Resistant Enterococcus faecium

    Enterococcus faecium has become a major opportunistic pathogen with the emergence of vancomycin-resistant enterococci (VRE). As part of the gut microbiota, they have to cope with numerous stresses, including effects of antibiotics and other xenobiotics, especially in patients hospitalized in intensive care units (ICUs) who receive many medications. The aim of this...

    Christophe Isnard, Sara B. Hernandez, François Guérin, Fanny Joalland, Didier Goux, François Gravey, Michel Auzou, David Enot, Pierrick Meignen, Jean-Christophe Giard, Felipe Cava, Vincent Cattoir
  • Open Access
    Anidulafungin and Micafungin Concentrations in Cerebrospinal Fluid and in Cerebral Cortex
    Pharmacology
    Anidulafungin and Micafungin Concentrations in Cerebrospinal Fluid and in Cerebral Cortex

    Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01 to 0.66 μg/ml) and micafungin levels (<0.01 to 0.16 μg/ml) were lower than those in plasma concentrations (0.77 to 5.07 and 1.21 to 8.70 μg/ml, respectively) drawn simultaneously. In cerebral cortex, anidulafungin and micafungin levels were 0.21 to 2.34...

    Jana Marx, René Welte, Tiziana Gasperetti, Patrizia Moser, Ronny Beer, Martin Ortler, Martina Jeske, Ramona Stern, Andreas Pomaroli, Michael Joannidis, Romuald Bellmann
  • Detection of <span class="named-content genus-species" id="named-content-1">Candida auris</span> Antifungal Drug Resistance Markers Directly from Clinical Skin Swabs
    Mechanisms of Resistance
    Detection of Candida auris Antifungal Drug Resistance Markers Directly from Clinical Skin Swabs

    Accurate and rapid assessment of Candida auris antifungal drug resistance is crucial for effective infection prevention and control actions, as well as for patient management. Here, performance of a molecular diagnostic platform, enabling rapid identification of FKS1 and ERG11 mutations conferring echinocandin and azole resistance, respectively, was...

    Milena Kordalewska, Annie Lee, Yanan Zhao, David S. Perlin
  • <em>In Vitro</em> Activity of Ibrexafungerp, a Novel Glucan Synthase Inhibitor against <span class="named-content genus-species" id="named-content-1">Candida glabrata</span> Isolates with <em>FKS</em> Mutations
    Susceptibility
    In Vitro Activity of Ibrexafungerp, a Novel Glucan Synthase Inhibitor against Candida glabrata Isolates with FKS Mutations

    Ibrexafungerp is a first-in-class glucan synthase inhibitor. In vitro activity was determined for 89 Candida glabrata isolates with molecularly identified FKS1 or FKS2 mutations conferring resistance to the echinocandins. All isolates were resistant to at least one echinocandin (i.e., anidulafungin, caspofungin, or micafungin) by broth...

    Natalie S. Nunnally, Kizee A. Etienne, David Angulo, Shawn R. Lockhart, Elizabeth L. Berkow
  • EUCAST Reference Testing of Rezafungin Susceptibility and Impact of Choice of Plastic Plates
    Susceptibility
    EUCAST Reference Testing of Rezafungin Susceptibility and Impact of Choice of Plastic Plates

    Rezafungin is a new long-acting echinocandin currently in phase 3 development. Epidemiological cutoff values are necessary for breakpoint setting but have not been established due to unexplained interlaboratory MIC variations observed in a prior multicenter study. Here we investigated if the choice of microtiter plates affected the variability when anidulafungin was included as a comparator.

    Maiken Cavling Arendrup, Karin Meinike Jørgensen, Rasmus Krøger Hare, Manuel Cuenca-Estrella, Oscar Zaragoza
  • Link between Heat Shock Protein 90 and the Mitochondrial Respiratory Chain in the Caspofungin Stress Response of <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span>
    Mechanisms of Resistance
    Link between Heat Shock Protein 90 and the Mitochondrial Respiratory Chain in the Caspofungin Stress Response of Aspergillus fumigatus

    Aspergillus fumigatus is an opportunistic mold responsible for invasive aspergillosis. Triazoles (e.g., voriconazole) represent the first-line treatment, but emerging resistance is of concern.

    M. Aruanno, D. Bachmann, D. Sanglard, F. Lamoth
  • A Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in <em>Candida</em> Species
    Mechanisms of Resistance
    A Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida Species

    The increasing incidence of and high mortality rates associated with invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. In addition to microbiological resistance to existing antifungal drugs, the large number of unexplained treatment failures is a serious concern.

    Arielle Butts, Parker Reitler, Andrew T. Nishimoto, Christian DeJarnette, Leanna R. Estredge, Tracy L. Peters, Michael P. Veve, P. David Rogers, Glen E. Palmer
  • Detection of Echinocandin-Resistant <em>Candida glabrata</em> in Blood Cultures Spiked with Different Percentages of <em>FKS2</em> Mutants
    Susceptibility
    Detection of Echinocandin-Resistant Candida glabrata in Blood Cultures Spiked with Different Percentages of FKS2 Mutants

    Infections caused by the coexistence of Candida glabrata echinocandin-resistant and echinocandin-susceptible cells may be possible, and the detection of FKS mutants when the proportions of FKS mutants are underrepresented poses a problem. We assessed the role of EUCAST and methods directly performed on positive blood cultures—Etest (ETDIR...

    María Ángeles Bordallo-Cardona, Carlos Sánchez-Carrillo, Emilio Bouza, Patricia Muñoz, Pilar Escribano, Jesús Guinea
  • Site-Directed Mutagenesis of the 1,3-β-Glucan Synthase Catalytic Subunit of <em>Pneumocystis jirovecii</em> and Susceptibility Assays Suggest Its Sensitivity to Caspofungin
    Susceptibility
    Site-Directed Mutagenesis of the 1,3-β-Glucan Synthase Catalytic Subunit of Pneumocystis jirovecii and Susceptibility Assays Suggest Its Sensitivity to Caspofungin

    The echinocandin caspofungin inhibits the catalytic subunit Gsc1 of the enzymatic complex synthesizing 1,3-β-glucan, an essential compound of the fungal wall. Studies with rodents showed that caspofungin is effective against Pneumocystis asci.

    A. Luraschi, S. Richard, P. M. Hauser

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