Journal ArticleDOI
Isavuconazole Treatment for Mucormycosis: A Single-Arm Open-Label Trial and Case-Control Analysis
Francisco M. Marty,Luis Ostrosky-Zeichner,Oliver A. Cornely,Kathleen M. Mullane,John R. Perfect,George Richard Thompson,George J Alangaden,Janice M. Brown,David N. Fredricks,Werner J. Heinz,Raoul Herbrecht,Nikolai Klimko,Galina Klyasova,Johan Maertens,Sameer R. Melinkeri,Ilana Oren,Peter G. Pappas,Zdeněk Ráčil,Galia Rahav,Rodrigo Ribeiro dos Santos,Stefan Schwartz,Jörg Janne Vehreschild,Jo Anne H. Young,Ploenchan Chetchotisakd,Sutep Jaruratanasirikul,Souha S. Kanj,Marc Engelhardt,Achim Kaufhold,Masanori Ito,Misun Lee,Carolyn Sasse,Rochelle Maher,Bernhardt Zeiher,Maria J G T Vehreschild +33 more
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Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B, and can be used for treatment of mucormYcosis and is well tolerated.Abstract:
Summary Background Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. Methods In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response—ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)—according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Findings Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19–179, range 2–882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595). Interpretation Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated. Funding Astellas Pharma Global Development, Basilea Pharmaceutica International.read more
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Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium
Oliver A. Cornely,Ana Alastruey-Izquierdo,Dorothee Arenz,Sharon C.-A. Chen,Eric Dannaoui,Bruno Hochhegger,Bruno Hochhegger,Martin Hoenigl,Martin Hoenigl,Henrik Jeldtoft Jensen,Katrien Lagrou,Russell E. Lewis,Sibylle C. Mellinghoff,Mervyn Mer,Zoi D. Pana,Danila Seidel,Donald C. Sheppard,Roger Wahba,Murat Akova,Alexandre Alanio,Abdullah M. S. Al-Hatmi,Sevtap Arikan-Akdagli,Hamid Badali,Ronen Ben-Ami,Alexandro Bonifaz,Stéphane Bretagne,Elio Castagnola,Methee Chayakulkeeree,Arnaldo Lopes Colombo,Dora E. Corzo-Leon,Lubos Drgona,Andreas H. Groll,Jesús Guinea,Jesús Guinea,Claus Peter Heussel,Ashraf S. Ibrahim,Souha S. Kanj,Nikolay Klimko,Michaela Lackner,Frédéric Lamoth,Fanny Lanternier,Cornelia Lass-Floerl,Dong-Gun Lee,Thomas Lehrnbecher,Badre E. Lmimouni,Mihai Mares,Georg Maschmeyer,Jacques F. Meis,Joseph Meletiadis,Joseph Meletiadis,C. Orla Morrissey,Marcio Nucci,Rita O. Oladele,Livio Pagano,Alessandro C. Pasqualotto,Atul Patel,Zdenek Racil,Malcolm Richardson,Emmanuel Roilides,Markus Ruhnke,Seyedmojtaba Seyedmousavi,Seyedmojtaba Seyedmousavi,Neeraj Sidharthan,Nina Singh,Janos Sinko,Anna Skiada,Monica A. Slavin,Monica A. Slavin,Rajeev Soman,Brad Spellberg,William J. Steinbach,Ban Hock Tan,Andrew J. Ullmann,Joerg J. Vehreschild,Maria J G T Vehreschild,Thomas J. Walsh,P. Lewis White,Nathan P. Wiederhold,Theoklis E. Zaoutis,Arunaloke Chakrabarti +79 more
TL;DR: Management of mucormycosis depends on recognising disease patterns and on early diagnosis, and limited availability of contemporary treatments burdens patients in low and middle income settings.
Journal ArticleDOI
Global Epidemiology of Mucormycosis
TL;DR: With the change in epidemiology of mucormycosis country-wise studies are warranted to estimate disease burden in different risk groups, analyse the clinical disease pattern and identify the new etiological agents.
Journal ArticleDOI
Challenges in the diagnosis and treatment of mucormycosis.
Anna Skiada,Cornelia Lass-Floerl,Nikolay Klimko,Ashraf S. Ibrahim,Ashraf S. Ibrahim,Emmanuel Roilides,George Petrikkos +6 more
TL;DR: The armamentarium of antifungals is slightly enriched by the addition of two newer azoles (posaconazole and isavuconazole) to liposomal amphotericin B, which remains the drug of choice for the initial antIfungal treatment, according to the recently published guidelines by ECIL-6.
Journal ArticleDOI
A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment
Hariprasath Prakash,Anup K. Ghosh,Shivaprakash M Rudramurthy,Pankaj Singh,Immaculata Xess,Jayanthi Savio,Umabala Pamidimukkala,Joseph Jillwin,Subhash Varma,Ashim Das,Naresh K. Panda,Surjit Singh,Amanjit Bal,Arunaloke Chakrabarti +13 more
TL;DR: Higher number of mucormycosis cases in uncontrolled diabetics of north India and emergence of R. microsporus and R. homothallicus across India causing the disease are highlighted.
Journal ArticleDOI
Epidemiology of Mucormycosis in India.
TL;DR: The exact incidence of mucormycosis in India is unknown due to the lack of population-based studies as discussed by the authors, however, the estimated prevalence of the disease is around 70 times higher in India than that in global data.
References
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Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group
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Epidemiology and Outcome of Zygomycosis: A Review of 929 Reported Cases
Maureen Roden,Theoklis E. Zaoutis,Wendy Buchanan,Tena A. Knudsen,Tatyana A. Sarkisova,Robert L. Schaufele,Michael Sein,Tin Sein,Christine C. Chiou,Jaclyn H. Chu,Dimitrios P. Kontoyiannis,Thomas J. Walsh +11 more
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Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database
Dimitrios P. Kontoyiennis,Kieren A. Marr,Benjamin J. Park,Barbara D. Alexander,Elias Anaissie,Thomas J. Walsh,James I. Ito,David R. Andes,John W. Baddley,Janice M. Brown,Lisa Brumble,Alison G. Freifeld,Susan Hadley,Loreen A. Herwaldt,Carol A. Kauffman,Katherine M. Knapp,G. Marshall Lyon,Vicki A. Morrison,Genovefa A. Papanicolaou,Thomas F. Patterson,Trish M. Perl,Mindy G. Schuster,Randall C. Walker,Kathleen A. Wannemuehler,John R. Wingard,Tom M. Chiller,Peter G. Pappas +26 more
TL;DR: In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis, and understanding the epidemiologic trends and burden of IFI may lead to improved management strategies and study design.
Journal ArticleDOI
Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.
Thomas J. Walsh,Hedy Teppler,Gerald R. Donowitz,Johan Maertens,Lindsey R. Baden,Anna Dmoszynska,Oliver A. Cornely,Michael R. Bourque,Robert J. Lupinacci,Carole A. Sable,Ben E. dePauw +10 more
TL;DR: Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.
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