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Eris Tollkuci
Midostaurin is the first approved FMS-related tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 mutated acute myeloid leukemia. Midostaurin is a major cytochrome P450 3A4 (CYP3A4) substrate. Coadministration with a strong CYP3A4 inhibitor or inducer can lead to a potential increase or decrease in midostaurin exposure. This report describes a 43-year-old patient with FLT3-internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia who initially presented with leukocytosis and concern for acute leukemia...
January 1, 2018: Journal of Oncology Pharmacy Practice
M-P Ledoux, J Denis, Y Nivoix, R Herbrecht
Isavuconazole, the active moiety of its prodrug isavuconazonium, is a new extended-spectrum triazole whose activity against yeasts, molds, including Aspergillus and mucorales, and dimorphic fungi has been shown in vitro and in preclinical models. The most relevant pharmacokinetics features are water-solubility of the prodrug, rapid cleavage of the prodrug into active moiety and cleavage product by plasmatic esterases, high oral bioavailability of isavuconazole with an extensive penetration into most tissues and a good safety profile even in case of renal impairment...
March 15, 2018: Journal de Mycologie Médicale
A J Ullmann, J M Aguado, S Arikan-Akdagli, D W Denning, A H Groll, K Lagrou, C Lass-Flörl, R E Lewis, P Munoz, P E Verweij, A Warris, F Ader, M Akova, M C Arendrup, R A Barnes, C Beigelman-Aubry, S Blot, E Bouza, R J M Brüggemann, D Buchheidt, J Cadranel, E Castagnola, A Chakrabarti, M Cuenca-Estrella, G Dimopoulos, J Fortun, J-P Gangneux, J Garbino, W J Heinz, R Herbrecht, C P Heussel, C C Kibbler, N Klimko, B J Kullberg, C Lange, T Lehrnbecher, J Löffler, O Lortholary, J Maertens, O Marchetti, J F Meis, L Pagano, P Ribaud, M Richardson, E Roilides, M Ruhnke, M Sanguinetti, D C Sheppard, J Sinkó, A Skiada, M J G T Vehreschild, C Viscoli, O A Cornely
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended...
March 12, 2018: Clinical Microbiology and Infection
A Skiada, C Lass-Floerl, N Klimko, A Ibrahim, E Roilides, G Petrikkos
The diagnosis and treatment of mucormycosis are challenging. The incidence of the disease seems to be increasing. Hematological malignancies are the most common underlying disease in countries with high income and uncontrolled diabetes in developing countries. Clinical approach to diagnosis lacks sensitivity and specificity. Radiologically, multiple (≥10) nodules and pleural effusion are reportedly associated with pulmonary mucormycosis. Another finding on computerized tomography (CT) scan, which seems to indicate the presence of mucormycosis, is the reverse halo sign...
April 1, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
J Denis, M-P Ledoux, Y Nivoix, R Herbrecht
Triazoles compounds are first-line agents for the treatment of invasive fungal diseases. Isavuconazole is the most recent triazole compound, approved in 2015 by the FDA and the EMA to treat invasive aspergillosis and mucormycosis. We reviewed here the in vitro activity of isavuconazole against a vast spectrum of species. Isavuconazole MICs were evaluated using CLSI, EUCAST or Etest methods, with no significant differences between the technics. Low MIC50 and MIC90 (<1μg/mL) were described for isavuconazole against the majority of Candida spp...
March 10, 2018: Journal de Mycologie Médicale
Galen M Kabulski, Shawn H MacVane
Previous studies of patients with cystic fibrosis (CF) treated with azole antifungals have shown altered pharmacokinetics relative to healthy patients. Data regarding the pharmacokinetic profile of isavuconazole in patients with CF undergoing lung transplantation is currently not available. Serum trough concentrations assessed in a single CF patient following transplant revealed significantly lower values relative to available literature. Larger studies are required to validate CF population pharmacokinetics of isavuconazole...
March 7, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Evgeny A Idelevich, Uwe Groß, Karsten Becker, Oliver Bader
Gradient diffusion assays Etest and MIC Test Strip for itraconazole, posaconazole and voriconazole as well as isavuconazole (MIC Test Strip) were evaluated for Aspergillus fumigatus against EUCAST broth microdilution. Both assays demonstrated generally good performance; however, posaconazole MIC Test Strip showed low agreement with broth microdilution due to MIC overestimation.
January 9, 2018: Diagnostic Microbiology and Infectious Disease
Chayanika Biswas, Derek Law, Michael Birch, Catriona Halliday, Tania C Sorrell, John Rex, Monica Slavin, Sharon C-A Chen
We determined the in vitro activity of the novel orotomide antifungal, F901318, against 30 Lomentospora prolificans, 20 Scedosporium apiospermum, 7 S. aurantiacum, and 3 S. boydii, isolates in comparison with standard antifungals. Against L. prolificans, F901318 was the most potent compound (MIC90 0.25 μg/ml); the geometric mean MIC (0.26 μg/ml) was significantly lower (23-80-fold) than those of itraconazole, voriconazole, posaconazole, and isavuconazole (all P < .001), and amphotericin B (P < .05)...
January 22, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
James M Kidd, Lindsay M Avery, Tomefa E Asempa, David P Nicolau, Joseph L Kuti
PURPOSE: Meropenem/vaborbactam is a novel intravenous antibiotic combining the carbapenem, meropenem, with a novel β-lactamase inhibitor, vaborbactam. Meropenem/vaborbactam is administered as a 3-hour infusion given every 8 hours, thereby potentially restricting an intravenous line for 9 h/d. Intravenous medications may be given concurrently via Y-site when compatibility data are available. Herein, physical compatibility was determined for the identification which medications can be coadministered with meropenem/vaborbactam via Y-site...
December 28, 2017: Clinical Therapeutics
Alessio Mesini, Giuliana Cangemi, Elena Palmisani, Carlo Dufour, Elio Castagnola
No abstract text is available yet for this article.
December 26, 2017: Journal of Chemotherapy
Dimitrios P Kontoyiannis, Dominik Selleslag, Kathleen Mullane, Oliver A Cornely, William Hope, Olivier Lortholary, Rodney Croos-Dabrera, Christopher Lademacher, Marc Engelhardt, Thomas F Patterson
Background: Historically, baseline neutropenia and lack of neutrophil recovery have been associated with poor outcomes in invasive aspergillosis (IA). It is unclear how treatment with the new Aspergillus-active triazoles isavuconazole and voriconazole affects outcomes in neutropenic patients with IA. Methods: A post hoc analysis of the Phase 3 SECURE trial assessed patients with neutropenia (neutrophil count <0.5 × 109/L for >10 days at baseline) with IA (proven/probable) who had received either isavuconazole or voriconazole...
November 29, 2017: Journal of Antimicrobial Chemotherapy
Ana Daniela Castrejón-Pérez, Esperanza C Welsh, Ivett Miranda, Jorge Ocampo-Candiani, Oliverio Welsh
Cutaneous mucormycosis is an emerging fungal infection caused by opportunistic fungi of the phylum Glomeromycota. It is frequent in poorly controlled diabetic patients and individuals with immunosuppression. It is usually acquired by direct inoculation through trauma. The clinical presentation is nonspecific, but an indurated plaque that rapidly evolves to necrosis is a common finding. Diagnosis should be confirmed by demonstration of the etiological agent and new molecular diagnostic tools have recently been described...
May 2017: Anais Brasileiros de Dermatologia
Sibylle C Mellinghoff, Matteo Bassetti, Daniela Dörfel, Stefan Hagel, Nicola Lehners, Andrzej Plis, Enrico Schalk, Antonio Vena, Oliver A Cornely
Isavuconazole is a novel antifungal drug approved for the treatment of adults with invasive aspergillosis and mucormycosis. While azoles as a class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in a dose-related manner. Here, we assessed the effects of isavuconazole on the length of QTc interval. The objective of the study was to describe changes in the QTc interval induced by isavuconazole treatment. A total of 26 adult patients from 7 hospitals were included...
November 25, 2017: Mycoses
Jochem B Buil, Roger J M Brüggemann, Roeland E Wasmann, Jan Zoll, Jacques F Meis, Willem J G Melchers, Johan W Mouton, Paul E Verweij
No abstract text is available yet for this article.
January 1, 2018: Journal of Antimicrobial Chemotherapy
Martin Hoenigl, Juergen Prattes, Peter Neumeister, Albert Wölfler, Robert Krause
Recent years have seen important advances in the diagnosis of invasive pulmonary aspergillosis (IPA), complemented by the introduction of new therapies. Despite this, IPA remains a major cause of infection-related mortality in patients with haematological diseases. There are two main reasons for this. First, diagnosis of IPA remains a challenge, since risk factors and the clinical, radiological and mycological presentations vary not only by fungal disease stage, but also by patient group (eg neutropenic vs non-neutropenic patients)...
March 2018: Mycoses
Kyle John Wilby
Invasive fungal infections are a major cause of morbidity and mortality, especially for immunocompromised patients. Treatment options are few and most are limited by safety and formulation concerns. Isavuconazole is a new triazole antifungal agent with official indications for the treatment of invasive fungal infections caused by Aspergillus and Mucormycosis. Its clinical efficacy has been proven in two landmark trials, SECURE and VITAL. This review aims to summarize and evaluate the published literature reporting clinical pharmacokinetic and pharmacodynamic outcome data of isavuconazole in humans...
November 4, 2017: European Journal of Drug Metabolism and Pharmacokinetics
Jochem B Buil, Roger J M Brüggemann, Roeland E Wasmann, Jan Zoll, Jacques F Meis, Willem J G Melchers, Johan W Mouton, Paul E Verweij
Introduction: Isavuconazole is a new triazole approved for the treatment of invasive aspergillosis. We investigated isavuconazole MIC distributions, isavuconazole MIC correlations with those of other azoles and pharmacodynamics of isavuconazole in low-level resistant Aspergillus fumigatus isolates. Methods: Isavuconazole, voriconazole, itraconazole and posaconazole susceptibility of 487 clinical A. fumigatus isolates was determined by EUCAST broth microdilution methodology...
January 1, 2018: Journal of Antimicrobial Chemotherapy
A Raffetin, V Courbin, V Jullien, E Dannaoui
The in vitro combinations of isavuconazole with echinocandins were evaluated against 30 Aspergillus spp. by a two-dimensional checkerboard microdilution method and an agar-based diffusion method. With the checkerboard method, the three combinations showed indifferent interactions for all the strains. With the agar-based method, indifferent interactions were found for all the strains for isavuconazole-micafungin and isavuconazole-anidulafungin. For the isavuconazole-caspofungin combination, indifference was found in 24/30 strains, synergy in 4/30 strains, and antagonism in 2/30 strains...
October 16, 2017: Antimicrobial Agents and Chemotherapy
Jarrett R Amsden, Paul O Gubbins
Triazole antifungal agents are prescribed to treat invasive fungal infections in neutropenic and non-neutropenic patients. These antifungal agents are substrates and inhibitors of cytochrome P450 (CYP). Genetic polymorphisms in CYP2C9, CYP2C19 and CYP3A5 can lead to large population-specific variations in drug efficacy and safety, optimal dosing, or contribute to drug interactions associated with this class. Areas covered: This manuscript reviews the pharmacogenomics (i.e. the influence of genetics on drug disposition) of triazole antifungal agents related to their CYP-mediated metabolism and summarizes their implications on triazole efficacy, safety, and tolerability...
November 2017: Expert Opinion on Drug Metabolism & Toxicology
Anne-Hortense Schmitt-Hoffmann, Kota Kato, Robert Townsend, Michael J Potchoiba, William W Hope, David Andes, Jochen Spickermann, Marlowe J Schneidkraut
Quantitative whole-body autoradiography was used to assess the distribution and tissue penetration of isavuconazole in rats following single and repeated oral-dose administration of radiolabeled isavuconazonium sulfate, the prodrug of isavuconazole. Following a single-dose administration of radiolabeled isavuconazonium sulfate (labeled on the active moiety), radioactivity was detectable within 1 h postdose in 56 of 65 tissue/fluid specimens. The highest maximum concentrations ( C max ) were observed in bile and liver (66...
December 2017: Antimicrobial Agents and Chemotherapy
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