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Aspergillus fumigatus

  • Azole and Amphotericin B MIC Values against <em>Aspergillus fumigatus</em>: High Agreement between Spectrophotometric and Visual Readings Using the EUCAST EDef 9.3.2 Procedure
    Susceptibility
    Azole and Amphotericin B MIC Values against Aspergillus fumigatus: High Agreement between Spectrophotometric and Visual Readings Using the EUCAST EDef 9.3.2 Procedure

    The EUCAST EDef 9.3.2 procedure recommends visual readings of azole and amphotericin B MICs against Aspergillus spp. Visual determination of MICs may be challenging. In this work, we aim to obtain and compare visual and spectrophotometric MIC readings of azoles and amphotericin B against Aspergillus fumigatus sensu lato isolates. A total of 847...

    Julia Serrano-Lobo, Ana Gómez, Waldo Sánchez-Yebra, Miguel Fajardo, Belén Lorenzo, Ferrán Sánchez-Reus, Inmaculada Vidal, Marina Fernández-Torres, Isabel Sánchez-Romero, Carlos Ruiz de Alegría-Puig, José Luis del Pozo, Patricia Muñoz, Pilar Escribano, Jesús Guinea
    and on behalf of the ASPEIN Study Group
  • <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> Cyp51A and Cyp51B Proteins Are Compensatory in Function and Localize Differentially in Response to Antifungals and Cell Wall Inhibitors
    Mechanisms of Resistance
    Aspergillus fumigatus Cyp51A and Cyp51B Proteins Are Compensatory in Function and Localize Differentially in Response to Antifungals and Cell Wall Inhibitors

    Triazole antifungals are the primary therapeutic option against invasive aspergillosis. However, resistance to azoles has increased dramatically over the last decade. Azole resistance is known to primarily occur due to point mutations in the azole target protein Cyp51A, one of two paralogous 14-α sterol demethylases found in Aspergillus fumigatus. Despite the...

    Mark T. Roundtree, Praveen R. Juvvadi, E. Keats Shwab, D. Christopher Cole, William J. Steinbach
  • Five-Year Survey (2014 to 2018) of Azole Resistance in Environmental <em>Aspergillus fumigatus</em> Isolates from China
    Susceptibility
    Five-Year Survey (2014 to 2018) of Azole Resistance in Environmental Aspergillus fumigatus Isolates from China

    A total of 191 soil samples from Hangzhou, China, were submitted to detect non-wild-type (non-WT) Aspergillus fumigatus and its associated mechanisms. There were 2 (4.7%), 13 (12.4%), and 31 (23.1%) isolates identified as non-WT in 2014, 2016, and 2018, respectively. The resistant mutations of TR34/L98H, TR46/Y121F/T289A, and TR34/L98H/S297T/F495I were found in 3, 5,...

    Duantao Cao, Ruilin Wu, Suxia Dong, Feiyan Wang, Chao Ju, Sumei Yu, Shiji Xu, Hua Fang, Yunlong Yu
  • A Simple Method To Detect Point Mutations in <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> <em>cyp51A</em> Gene Using a Surveyor Nuclease Assay
    Analytical Procedures
    A Simple Method To Detect Point Mutations in Aspergillus fumigatus cyp51A Gene Using a Surveyor Nuclease Assay

    One of the main mechanisms of azole resistance of Aspergillus fumigatus is thought to be a reduction in the drug’s affinity for the target molecule, Cyp51A, due to its amino acid mutation(s). It is known that the azole resistance pattern is closely related to the mutation site(s) of the molecule. In this study, we tried to develop a simple and rapid detection method...

    Teppei Arai, Hidetaka Majima, Akira Watanabe, Katsuhiko Kamei
  • <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> Clinical Isolates Carrying CYP51A with TR34/L98H/S297T/F495I Substitutions Detected after Four-Year Retrospective Azole Resistance Screening in Brazil
    Susceptibility
    Aspergillus fumigatus Clinical Isolates Carrying CYP51A with TR34/L98H/S297T/F495I Substitutions Detected after Four-Year Retrospective Azole Resistance Screening in Brazil

    Azole antifungal resistance in Aspergillus fumigatus is a worldwide concern. As in most public hospitals in Brazil, antifungal susceptibility tests are not routinely performed for filamentous fungi at our institution. A 4-year retrospective azole antifungal resistance screening revealed two azole-resistant...

    Laís Pontes, Caio Augusto Gualtieri Beraquet, Teppei Arai, Guilherme Leite Pigolli, Luzia Lyra, Akira Watanabe, Maria Luiza Moretti, Angélica Zaninelli Schreiber
  • Comparison of the MICs Obtained by Gradient Concentration Strip and EUCAST Methods for Four Azole Drugs and Amphotericin B against Azole-Susceptible and -Resistant <em>Aspergillus</em> Section <em>Fumigati</em> Clinical Isolates
    Susceptibility
    Comparison of the MICs Obtained by Gradient Concentration Strip and EUCAST Methods for Four Azole Drugs and Amphotericin B against Azole-Susceptible and -Resistant Aspergillus Section Fumigati Clinical Isolates

    Reference methods used to assess the drug susceptibilities of Aspergillus fumigatus isolates consisted of EUCAST and CLSI standardized broth microdilution techniques. Considering the increasing rate and the potential impact on the clinical outcome of azole resistance in A. fumigatus, more suitable...

    S. Dellière, L. Verdurme, J. Bigot, E. Dannaoui, Y. Senghor, F. Botterel, A. Fekkar, M. E. Bougnoux, C. Hennequin, J. Guitard
  • Efficacy of Voriconazole against <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> Infection Depends on Host Immune Function
    Mechanisms of Action: Physiological Effects
    Efficacy of Voriconazole against Aspergillus fumigatus Infection Depends on Host Immune Function

    Antifungal therapy can fail in a remarkable number of patients with invasive fungal disease, resulting in significant morbidity worldwide. A major contributor to this failure is that while these drugs have high potency in vitro, we do not fully understand how they work inside infected hosts.

    Emily E. Rosowski, Jiaye He, Jan Huisken, Nancy P. Keller, Anna Huttenlocher
  • Comparison of Two Typing Methods for Characterization of Azole Resistance in <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> from Potting Soil Samples in a Chinese Hospital
    Epidemiology and Surveillance
    Comparison of Two Typing Methods for Characterization of Azole Resistance in Aspergillus fumigatus from Potting Soil Samples in a Chinese Hospital

    To understand the characterizations of azole resistance in Aspergillus fumigatus from potting soil samples in the hospital, a total of 58 samples were collected. Among 106 A. fumigatus samples obtained, 5 isolates from 4 soil samples located in the gerontology department were identified as azole-...

    Hong Fan, Yong Chen, Liping Duan, Jingya Zhao, Chunping Qin, Haifeng Li, Jinke Sun, Li Han
  • 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
  • First-in-Human Phase 1 Study To Assess Safety, Tolerability, and Pharmacokinetics of a Novel Antifungal Drug, VL-2397, in Healthy Adults
    Clinical Therapeutics
    First-in-Human Phase 1 Study To Assess Safety, Tolerability, and Pharmacokinetics of a Novel Antifungal Drug, VL-2397, in Healthy Adults

    VL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal in vitro activity, and potent in vivo activity against Aspergillus fumigatus, including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study, was conducted in healthy adults to determine the...

    Mammen P. Mammen, Danielle Armas, Frank H. Hughes, Andrew M. Hopkins, Cindy L. Fisher, Pamela A. Resch, Denis Rusalov, Sean M. Sullivan, Larry R. Smith

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