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aspergillosis

  • Pharmacodynamics of Posaconazole in Experimental Invasive Pulmonary Aspergillosis: Utility of Serum Galactomannan as a Dynamic Endpoint of Antifungal Efficacy
    Clinical Therapeutics
    Pharmacodynamics of Posaconazole in Experimental Invasive Pulmonary Aspergillosis: Utility of Serum Galactomannan as a Dynamic Endpoint of Antifungal Efficacy

    Aspergillus galactomannan antigenemia is an accepted tool for the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Little is known, however, about the utility of this biomarker to assess the efficacy of antifungal therapies. The pharmacokinetics (PK) and pharmacodynamics (PD) of posaconazole in treatment and prophylaxis were investigated in the persistently neutropenic rabbit model of...

    Silke Gastine, William Hope, Georg Hempel, Ruta Petraitiene, Vidmantas Petraitis, Diana Mickiene, John Bacher, Thomas J. Walsh, Andreas H. Groll
  • Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis
    Pharmacology
    Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis

    Isavuconazole is the newest triazole antifungal, and it displays a favorable pharmacokinetic and safety profile. Less is known about its long-term use in immunocompetent hosts. We performed a retrospective service evaluation of isavuconazole therapeutic drug monitoring in patients with chronic pulmonary aspergillosis. Adverse events (AEs) and dose adjustments made during routine clinical practice were recorded, and AEs were classified...

    Chris Kosmidis, Akan Otu, Caroline B. Moore, Malcolm D. Richardson, Riina Rautemaa-Richardson
  • <em>In Vitro</em> Evaluation of Radiolabeled Amphotericin B for Molecular Imaging of Mold Infections
    Chemistry; Biosynthesis
    In Vitro Evaluation of Radiolabeled Amphotericin B for Molecular Imaging of Mold Infections

    Invasive pulmonary aspergillosis and mucormycosis are life-threatening complications in immunocompromised patients. A rapid diagnosis followed by early antifungal treatment is essential for patient survival. Given the limited spectrum of biomarkers for invasive mold infections, recent studies have proposed the use of radiolabeled siderophores or antibodies as molecular probes to increase the specificity of radiological findings by...

    Lukas Page, Andrew J. Ullmann, Fabian Schadt, Sebastian Wurster, Samuel Samnick
  • ASP2397 Is a Novel Natural Compound That Exhibits Rapid and Potent Fungicidal Activity against <em>Aspergillus</em> Species through a Specific Transporter
    Pharmacology
    ASP2397 Is a Novel Natural Compound That Exhibits Rapid and Potent Fungicidal Activity against Aspergillus Species through a Specific Transporter

    Current therapies against invasive pulmonary aspergillosis (IPA) have a limited cure rate. Given that a delay in treatment initiation may be fatal, a new drug with rapid-onset and potent fungicidal activity is needed. The novel cyclic hexapeptide ASP2397 (currently known as VL-2397) exhibited antifungal activity against Aspergillus fumigatus (including azole-sensitive...

    Ikuko Nakamura, Keisuke Ohsumi, Shinobu Takeda, Kiyomitsu Katsumata, Satoru Matsumoto, Souichiro Akamatsu, Hikaru Mitori, Toru Nakai
  • <em>Candida</em> in the Respiratory Tract Potentially Triggers Galactomannan Positivity in Nonhematological Patients
    Analytical Procedures
    Candida in the Respiratory Tract Potentially Triggers Galactomannan Positivity in Nonhematological Patients

    BAL fluid samples from critically ill patients shared a rate of 29% false-positive galactomannan results. We aimed to determine whether Candida species abundance in BAL fluid causes galactomannan (GM) positivity.

    M. Aigner, M. Wanner, P. Kreidl, C. Lass-Flörl, M. Lackner
  • Population Pharmacokinetic Modeling of VL-2397, a Novel Systemic Antifungal Agent: Analysis of a Single- and Multiple-Ascending-Dose Study in Healthy Subjects
    Clinical Therapeutics
    Population Pharmacokinetic Modeling of VL-2397, a Novel Systemic Antifungal Agent: Analysis of a Single- and Multiple-Ascending-Dose Study in Healthy Subjects

    VL-2397, a novel, systemic antifungal agent, has potent in vitro and in vivo fungicidal activity against Aspergillus species. Plasma concentrations from a phase 1 study were used to construct a population pharmacokinetic (PPK) model for VL-2397.

    Laura L. Kovanda, Sean M. Sullivan, Larry R. Smith, Amit V. Desai, Pete L. Bonate, William W. Hope
  • Magnitude of Voriconazole Resistance in Clinical and Environmental Isolates of <span class="named-content genus-species" id="named-content-1">Aspergillus flavus</span> and Investigation into the Role of Multidrug Efflux Pumps
    Mechanisms of Resistance
    Magnitude of Voriconazole Resistance in Clinical and Environmental Isolates of Aspergillus flavus and Investigation into the Role of Multidrug Efflux Pumps

    The magnitude of azole resistance in Aspergillus flavus and its underlying mechanism is obscure. We evaluated the frequency of azole resistance in a collection of clinical (n = 121) and environmental isolates (n = 68) of A. flavus by the broth microdilution method.

    ...
    Raees A. Paul, Shivaprakash M. Rudramurthy, Manpreet Dhaliwal, Pankaj Singh, Anup K. Ghosh, Harsimran Kaur, Subhash Varma, Ritesh Agarwal, Arunaloke Chakrabarti
  • Susceptibility
    Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study)

    Antifungal resistance is increasing by the emergence of intrinsically resistant species and by the development of secondary resistance in susceptible species. A previous study performed in Spain revealed levels of azole resistance in molds of between 10 and 12.7%, but secondary resistance in Aspergillus fumigatus was not detected.

    Ana Alastruey-Izquierdo, Laura Alcazar-Fuoli, Olga Rivero-Menéndez, Josefina Ayats, Carmen Castro, Julio García-Rodríguez, Lidia Goterris-Bonet, Elisa Ibáñez-Martínez, María José Linares-Sicilia, M. Teresa Martin-Gomez, Estrella Martín-Mazuelos, Teresa Pelaez, Javier Peman, Antonio Rezusta, Susana Rojo, Rocio Tejero, Diego Vicente Anza, Jesús Viñuelas, Maria Soledad Zapico, Manuel Cuenca-Estrella
    and on behalf of the FILPOP2 Project from GEMICOMED (SEIMC) and REIPI
  • Susceptibility
    Effect of the Novel Antifungal Drug F901318 (Olorofim) on Growth and Viability of Aspergillus fumigatus

    F901318 (olorofim) is a novel antifungal drug that is highly active against Aspergillus species. Belonging to a new class of antifungals called the orotomides, F901318 targets dihydroorotate dehydrogenase (DHODH) in the de novo pyrimidine biosynthesis pathway.

    Saskia du Pré, Nicola Beckmann, Mariana Cruz Almeida, Graham E. M. Sibley, Derek Law, Alexandra C. Brand, Mike Birch, Nick D. Read, Jason D. Oliver
  • Experimental Therapeutics
    Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis
    Alicia López-Sánchez, Alba Pérez-Cantero, Carlos Torrado-Salmerón, Adela Martin-Vicente, Víctor García-Herrero, María Ángeles González-Nicolás, Alberto Lázaro, Alberto Tejedor, Santiago Torrado-Santiago, Juan José García-Rodríguez, Javier Capilla, Susana Torrado

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