In Vitro Evaluation of Radiolabeled Amphotericin B for Molecular Imaging of Mold Infections.

In Vitro Evaluation of Radiolabeled Amphotericin B for Molecular Imaging of Mold Infections. Antimicrob Agents Chemother. 2020 May 11;: Authors: Page L, Ullmann AJ, Schadt F, Wurster S, Samnick S Abstract 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 radiolabeled siderophores or antibodies as molecular probes to increase the specificity of radiological findings by nuclear imaging modalities. While holding enormous diagnostic potential, most of the currently available molecular probes are tailored to the detection of Aspergillus species and their cost-intensive and sophisticated implementation restrict the accessibility at less specialized centers. In order to develop cost-efficient and broadly applicable tracers for pulmonary mold infections, this study established streamlined and high-yielding protocols to radiolabel amphotericin B (AMB) with the gamma-emitter technetium-99m (99mTc-AMB) and the positron-emitter gallium-68 (68Ga-AMB). Radiochemical purity of the resulting tracers consistently exceeded 99 % and both probes displayed excellent stability in human serum (> 98 % after 60-240 min at 37 °C). The uptake kinetics by representative mold pathogens were assessed in an in vitro Transwel...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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Conference abstracts
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
ron G Abstract 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 of three Aspergillus fumigatus clinical strains isolated from an Argentinian cystic fibrosis patient under long-term triazole treatment.Strain susceptibilities were assessed and CYP51A gene sequences were analyzed. Two of the studied Asp...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In conclusion, A. niger should be considered as a minority species in the section Nigri The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and gradient concentration strips methods require further investigation. PMID: 32312779 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated ...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Fungal and Parasitic Infections Source Type: research
Combination Therapy with Ibrexafungerp (formerly SCY-078), a First-in-Class Triterpenoid Inhibitor of (1→3)-β-D-Glucan Synthesis, and Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis. Antimicrob Agents Chemother. 2020 Mar 16;: Authors: Petraitis V, Petraitiene R, Katragkou A, Maung BBW, Naing E, Kavaliauskas P, Barat S, Borroto-Esoda K, Azie N, Angulo D, Walsh TJ Abstract Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1→3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo eff...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In this study, we have characterized recombinant AfERG10A as a functional acetyl-CoA acetyltransferase catalyzing both synthetic and degradative reactions. Unexpectedly, AfERG10A localizes to mitochondria in A. fumigatus as shown by C-terminal GFP-tag fusion. Both knockout and inducible promoter strategies demonstrate that Aferg10A is essential for the survival of A. fumigatus Reduced expression of Aferg10A leads to severe morphological defects and increased susceptibility to oxidative and cell wall stresses. Although the catalytic mechanism of acetyl-CoA acetyltransferase family is highly conserved, the crystal structure ...
Source: Applied and Environmental Microbiology - Category: Microbiology Authors: Tags: Appl Environ Microbiol Source Type: research
Abstract Azole antifungals 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 years retrospective azole antifungal resistance screening revealed the two azole-resistant A. fumigatus clinical isolates carrying CYP51A TR34/L98H/S297T/F495I mutation resistance mechanism obtained from two unrelated patients. Broth microdilution antifungal susceptibility showed high MICs for Itraconazole, Posaconazole, and Miconazole. STR typing analysis presented high similarity betw...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Conference abstracts
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Abstract 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 safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous (IV) doses of VL-2397. All dosing cohorts were fully enrolled; all subjects completed the safety follow-up. A safety committee reviewed the safety data for each dosing coh...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
h S Abstract Isavuconazole plasma concentrations were measured before and after Sustained Low-Efficiency Dialysis (SLED) treatment in 22 adult critically ill patients with probabale invasive aspergillosis and underlying hematological malignancies. Isavuconazole levels were significantly lower after SLED treatment (5.73 μg/ml vs. 3.36 μg/ml; p
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
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