Pharmacodynamics of isavuconazole in an Aspergillus fumigatus mouse infection model

Antimicrobial Agents and Chemotherapy
Seyedmojtaba SeyedmousaviJ W Mouton

Abstract

Azole resistance is an emerging problem in Aspergillus fumigatus which translates into treatment failure. Alternative treatments with new azoles may improve therapeutic outcome in invasive aspergillosis (IA) even for strains with decreased susceptibility to current azoles. The in vivo efficacy of 0.25, 1, 4, 16, 64, 128, 256, and 512 mg/kg of body weight/day prodrug isavuconazonium sulfate (BAL8557) (isavuconazole [ISA]-equivalent doses of 0.12, 0.48, 1.92, 7.68, 30.7, 61.4, 122.9, and 245.8 mg/kg/day, respectively) administered by oral gavage was assessed in an immunocompetent murine model of IA against four clinical A. fumigatus isolates: a wild-type isolate (ISA MICEUCAST, 0.5 mg/liter) and three azole-resistant isolates harboring substitutions in the cyp51A gene: G54W (ISA MIC(EUCAST), 0.5 mg/liter), M220I (ISA MIC(EUCAST), 4 mg/liter), and TR34/L98H (ISA MIC(EUCAST), 8 mg/liter). The maximum effect (100% survival) was reached at a prodrug isavuconazonium sulfate dose of 64 mg/kg for the wild-type isolate, 128 mg/kg for the G54W mutant, and 256 mg/kg two times per day (q12) for the M220I mutant. A maximum response was not achieved with the TR34/L98H isolates with the highest dose of prodrug isavuconazonium sulfate (256 mg/k...Continue Reading

References

Jan 1, 1993·The American Review of Respiratory Disease·P Von WichertW M Franck
Sep 1, 1996·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·D W Denning
Aug 9, 2002·The New England Journal of Medicine·Raoul HerbrechtUNKNOWN Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillu
Dec 27, 2002·The New England Journal of Medicine·Adilia WarrisPaul E Verweij
Jan 7, 2003·Infectious Disease Clinics of North America·Kieren A MarrDavid Denning
Mar 11, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ross SummerAlan Fine
Jul 2, 2004·American Journal of Respiratory and Critical Care Medicine·Wouter MeerssemanEric Van Wijngaerden
Oct 13, 2006·International Journal of Antimicrobial Agents·Susan J HowardDavid W Denning
Jul 10, 2007·Lancet·Coretta van Leer-ButerPaul E Verweij
Sep 12, 2007·Antimicrobial Agents and Chemotherapy·Sungmin Kiem, Jerome J Schentag
Feb 15, 2008·The Journal of Antimicrobial Chemotherapy·A C Pasqualotto, D W Denning
Jan 8, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Thomas J WalshUNKNOWN Infectious Diseases Society of America
Jan 15, 2008·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·UNKNOWN Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility T
Mar 11, 2008·The Journal of Antimicrobial Chemotherapy·C Martín de la EscaleraE Martín-Mazuelos
May 9, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ben De PauwUNKNOWN National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group
Jan 24, 2009·Antimicrobial Agents and Chemotherapy·Susanne PerkhoferUNKNOWN European Committee on Antimicrobial Susceptibility Testing
Mar 11, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jan W M van der LindenPaul E Verweij
Jul 25, 2009·Emerging Infectious Diseases·Susan J HowardDavid W Denning
Nov 3, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Paul E VerweijDavid W Denning
Nov 18, 2009·Antimicrobial Agents and Chemotherapy·Eleftheria MavridouPaul E Verweij
Jun 5, 2010·Mycopathologia·George R Thompson, Nathan P Wiederhold
Oct 18, 2011·Emerging Infectious Diseases·Jan W M van der LindenPaul E Verweij
Oct 27, 2011·The Journal of Antimicrobial Chemotherapy·Anuradha ChowdharyJacques F Meis
Nov 16, 2011·Future Microbiology·David W Denning, David S Perlin
Apr 26, 2012·Expert Opinion on Drug Metabolism & Toxicology·Joanne Livermore, William Hope
Jul 18, 2012·Polish journal of radiology·Anna Janik-MoszantTomasz Szczepański
Aug 15, 2012·Antimicrobial Agents and Chemotherapy·P-M RathJ Steinmann

❮ Previous
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Citations

Sep 17, 2015·Current Opinion in Infectious Diseases·Nathan P Wiederhold, Thomas F Patterson
Aug 19, 2015·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Paul E VerweijJ Peter Donnelly
Apr 17, 2016·The Journal of Antimicrobial Chemotherapy·Laura L KovandaWilliam W Hope
May 11, 2016·Expert Review of Clinical Pharmacology·Laura L KovandaWilliam W Hope
Oct 22, 2016·Drugs·Matt Shirley, Lesley J Scott
Jan 29, 2017·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Balthazar ToussaintVincent Jullien
Mar 15, 2018·Medical Mycology·Agustin Resendiz SharpeUNKNOWN ISHAM/ECMM Aspergillus Resistance Surveillance working group
Oct 28, 2015·Antimicrobial Agents and Chemotherapy·Helen BoxWilliam W Hope
Sep 20, 2017·Antimicrobial Agents and Chemotherapy·Amit V DesaiPeter L Bonate
Oct 4, 2017·Antimicrobial Agents and Chemotherapy·Anne-Hortense Schmitt-HoffmannMarlowe J Schneidkraut
Jun 22, 2016·Antimicrobial Agents and Chemotherapy·Nathan P WiederholdThomas F Patterson
Nov 27, 2019·Antimicrobial Agents and Chemotherapy·Xuemei WuM Hong Nguyen
Sep 12, 2018·Antimicrobial Agents and Chemotherapy·John M GuestAshok Kumar
Sep 16, 2017·The Journal of Infectious Diseases·Russell E Lewis, Paul E Verweij
Mar 24, 2020·Current Fungal Infection Reports·Victoria M StevensTyree H Kiser
Sep 16, 2017·The Journal of Infectious Diseases·Anuradha ChowdharyJacques F Meis
May 5, 2018·Clinical Pharmacokinetics·Matthew W McCarthyVidmantas Petraitis
Oct 12, 2018·Drugs in R&D·Léa DarnaudPeggy Gandia
Nov 14, 2019·International Journal of Molecular Sciences·Hnin Phyu LwinKwang-Soo Shin
Jan 13, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Jacques F MeisPaul E Verweij
Jun 1, 2017·Frontiers in Microbiology·Guillaume Desoubeaux, Carolyn Cray
Mar 31, 2021·Antimicrobial Agents and Chemotherapy·Laura L KovandaDavid A Stevens
May 27, 2021·Studies in Mycology·A ArastehfarM Hoenigl

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