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Global Guideline for the Diagnosis and Management of Mucormycosis

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Global Guideline for the Diagnosis and Management of Mucormycosis Review 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, Martin Hoenigl, Henrik E 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 L Colombo, Dora E Corzo-León, Lubos Drgona, Andreas H Groll, Jesus Guinea, Claus-Peter Heussel, Ashraf S Ibrahim, Souha S Kanj, Nikolay Klimko, Michaela Lackner, Frederic Lamoth, Fanny Lanternier, Cornelia Lass-Floerl, Dong-Gun Lee, Thomas Lehrnbecher, Badre E Lmimouni, Mihai Mares, Georg Maschmeyer, Jacques F Meis, Joseph Meletiadis, C Orla Morrissey, Marcio Nucci, Rita Oladele, Livio Pagano, Alessandro Pasqualotto, Atul Patel, Zdenek Racil, Malcolm Richardson, Emmanuel Roilides, Markus Ruhnke, Seyedmojtaba Seyedmousavi, Neeraj Sidharthan, Nina Singh, János Sinko, Anna Skiada, Monica Slavin, Rajeev Soman, Brad Spellberg, William Steinbach, Ban Hock Tan, Andrew J Ullmann, Jörg J Vehreschild, Maria J G T Vehreschild, Thomas J Walsh, P Lewis White, Nathan P Wiederhold, Theoklis Zaoutis, Arunaloke Chakrabarti, for the Mucormycosis ECMM MSG Global Guideline Writing Group Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, Lancet Infect Dis 2019 and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex Published Online multidisciplinary management has potential to improve prognosis, but approaches differ between health-care November 4, 2019 https://doi.org/10.1016/ settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence S1473-3099(19)30312-3 on mucormycosis management and provided consensus recommendations addressing differences between the Department I of Internal regions of the world as part of the “One World One Guideline” initiative of the European Confederation of Medical Medicine, University Hospital Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of of Cologne, Cologne, Germany mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by (O A Cornely MD, D Arenz PhD, strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is J J Vehreschild MD, M J G T Vehreschild MD, strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are S C Mellinghoff MD, recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B D Seidel PhD); German Centre deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited for Infection Research (DZIF) partner site Bonn-Cologne, settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited Cologne, Germany (O A Cornely, availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty J J Vehreschild, were identified and future research directions specified. M J G T Vehreschild); CECAD Cluster of Excellence, University of Cologne, Cologne, Introduction availability of new formulations of posaconazole. More­ Germany (O A Cornely, D Arenz, Suspected mucormycosis requires urgent intervention, over, previous guide lines did not include comprehensive S C Mellinghoff, D Seidel); because of the often rapidly progressive and destructive clinical and radio logical imaging, pathological and Clinical Trials Center Cologne, nature of the infection.1,2 Delayed initiation of therapy histological findings, nor did they provide details University Hospital of Cologne, 1 Cologne, Germany is associated with increased mortality. Maximising on surgery as a core element of mucormycosis (O A Cornely); Mycology survival rates requires rapid diagnostic and therapeutic management. Reference Laboratory, National inter vention, including immediate involvement of a multi­ The European Confederation of Medical Mycology Centre for Microbiology, disciplinary medical, surgical, radiological, and laboratory­ (ECMM), together with the Mycoses Study Group Instituto de Salud Carlos III, 3 Madrid, Spain based team. Readily available guidance is important to Education & Research Consortium (MSG ERC), issues (A Alastruey-Izquierdo PhD); ensure efficient diagnosis and treatment, and to optimise this comprehensive guidance document to facilitate Centre for Infectious Diseases patient prognosis. Optimal management depends on clinical decision­making, and simultaneously provides and Microbiology Laboratory recognising disease patterns and the available diagnostic an overview of the areas of uncertainty in the field.9,10 Services, New South Wales Health Pathology, and the and therapeutic options, which differ between the regions We aimed to address limitations of previous recom­ Department of Infectious of the world. mendations, by engaging physicians and scientists Diseases, Westmead Hospital, Currently available guidelines are limited to specific involved in various aspects of mucormycosis manage­ School of Medicine, University patient groups in haematology,4 or a specific geographical ment, representing the fields of microbiology, pathology, of Sydney, Sydney, NSW, Australia (S C-A Chen PhD); 5 6–8 region, or require an update. Recently, several critical radio logy, infectious diseases, surgery, paediatrics, haema­ Université Paris-Descartes, developments have fundamentally changed the manage­ tology, intensive care, dermatology, and pharm cology. In Faculté de Médecine, APHP, ment of this condition. These include the development addi tion, the guideline group comprises experts from Hôpital Européen Georges of new and more widely used molecular techniques all parts of the world and provides management Pompidou, Unité de Parasitologie-Mycologie, for the diagnosis of mucormycosis, the licensing of pathways for different regional environ ments (panel; for Service de Microbiologie, Paris, isavuconazole for treatment of mucormycosis, and the further infor mation on guideline development, systematic France (E Dannaoui MD); www.thelancet.com/infection Published online November 4, 2019 http://dx.doi.org/10.1016/S1473-3099(19)30312-3 1 Review Radiology, Hospital São Lucas da Pontificia Universidade Panel: How the guideline group worked Catolica do Rio Grande do Sul (PUCRS), Escola de Medicina, In December, 2017, experts were identified based on their OR zygomyc* AND (case*[Title/Abstract] OR patient*[Title/ Porto Alegre, Brazil publication activity in the field of mucormycosis in the previous Abstract] OR report[Title/Abstract]) AND (“2013/01/01”[PDat] : (B Hochhegger MD); Radiology, 5 years, their involvement in patient management, and their “2017/12/31”[PDat])”. Universidade Federal de distribution over world regions defined by the United Nations. Ciências da Saúde de Porto From January to February, 2018, video conferences on the Alegre (UFCSPA), Porto Alegre, Experts were invited to develop this guideline in January, 2018. methodology were held, and a video tutorial added in Brazil (B Hochhegger); Section This guideline follows the structure and definitions of previous March, 2018. Assistance and supervision to the group were of Infectious Diseases and Tropical Medicine and Division guidelines on invasive fungal infections which are in accordance provided by the coordinators (OAC, AC). Documents were of Pulmonology, Medical with the Grading of Recommendations Assessment, shared among the authors on a password-protected OneDrive University of Graz, Graz, Development and Evaluation (GRADE) and Appraisal (Microsoft Corp, Redmont WA, USA) repository, and were Austria (M Hoenigl MD); of Guidelines for Research & Evaluation (AGREE) updated several times per day. Updates on PICO tables were Division of Infectious Diseases and Global Public Health, systems. The PICO (population, intervention, comparison, written in red font; after spellcheck and formatting font colour Department of Medicine, and outcome) approach is reflected by the tables. was changed to blue for consideration by the group. Contents University of California Both, diagnostic assays and treatment strategies might alter discussed and agreed on were changed to black font. Once all San Diego, San Diego, USA tables were finalised, a writing group (OAC, AAI, DA, SCAC, ED, (M Hoenigl); Faculty of Health patient course, and are thus regarded as interventions. First, a and Medical Sciences, population is defined; then the intention or objective is stated, BH, MH, HEJ, KL, REL, SCM, MMe, ZP, DS, DCS, RW, AC) University of Copenhagen, followed by the intervention. For such logical sequence, contributed the first draft, which was circulated to all Copenhagen, Denmark participants for approval in October, 2018. Recommendations (H E Jensen PhD); Department strength of recommendation (SOR) and quality of evidence were consensus-based. If no consensus was found, majority of Microbiology, Immunology (QOE) are provided, followed by the references on which the
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