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Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study - 25/05/23

Doi : 10.1016/S1473-3099(22)00872-6 
Martin Hoenigl, ProfMD a, b, c, , Jon Salmanton-García, PhD d, f, h, Matthias Egger, MD a, b, Jean-Pierre Gangneux, ProfMD i, Tihana Bicanic, MD j, Sevtap Arikan-Akdagli, ProfMD k, Ana Alastruey-Izquierdo, PhD m, Nikolai Klimko, ProfMD n, Aleksandra Barac, MD o, Volkan Özenci, ProfMD q, r, Eelco F J Meijer, MD t, u, v, Nina Khanna, MD w, Matteo Bassetti, ProfMD x, y, Riina Rautemaa-Richardson, MD z, aa, Katrien Lagrou, ProfPharmD ab, ac, Kai-Manuel Adam, MD w, Emin Halis Akalin, ProfMD ad, Murat Akova, ProfMD l, Valentina Arsic Arsenijevic, MD p, ae, Avinash Aujayeb, MD af, Ola Blennow, MD s, Stéphane Bretagne, ProfMD ag, François Danion, MD aj, Blandine Denis, MD ah, Nick Alexander de Jonge, MD ak, Guillaume Desoubeaux, ProfMD al, Lubos Drgona, MD am, Nurettin Erben, MD an, Andrea Gori, MD ao, ap, Julio García Rodríguez, PhD aq, Carolina Garcia-Vidal, MD ar, Daniele Roberto Giacobbe, MD x, y, Anna L Goodman, MD as, at, Petr Hamal, MD au, Helena Hammarström, MD av, Cristina Toscano, MD aw, Fanny Lanternier, ProfMD ai, Cornelia Lass-Flörl, ProfMD ax, Deborah E A Lockhart, PhD ay, az, Thomas Longval, MD ba, Laura Loughlin, MD bb, Tadeja Matos, MD bc, Malgorzata Mikulska, ProfMD x, y, Manjusha Narayanan, FRCPath bd, Sonia Martín-Pérez, MD be, Juergen Prattes, MD a, b, c, f, Benedict Rogers, MBChB bf, Laman Rahimli, MD d, f, h, Maite Ruiz, PhD bg, bh, Emmanuel Roilides, ProfMD bi, Michael Samarkos, ProfMD bj, Ulrike Scharmann, MD bk, Uluhan Sili, ProfMD bl, Oguz Resat Sipahi, ProfMD bm, Alena Sivakova, MD bn, Joerg Steinmann, ProfMD bk, bo, Janina Trauth, MD bp, Ozge Turhan, ProfMD bq, Jens Van Praet, MD br, Antonio Vena, PhD x, y, P Lewis White, ProfPhD bs, bt, Birgit Willinger, ProfMD bu, Anna Maria Tortorano, PhD bv, Maiken C Arendrup, ProfMD bw, bx, by, Philipp Koehler, MD d, f, h, bz, *, Oliver A Cornely, ProfMD d, e, f, g, h, bz, *
on behalf of the

ECMM Candida III Study Group

  Members listed at the end of the Article
Mario Tumbarello, Alida Fe Talento, Alba C Ruiz, Zdenek Racil, Igor Stoma, Maria Calbacho, Eric Van Wijngaerden, Júlia Henriques, Harriett Jordan, Valentina Ferroni, Ozlem Koyuncu Ozyurt, Christopher Milacek, Robert Krause, Christoph Zurl, Matthijs Backx, Ang Li, Raphael Seufert, Rok Tomazin, Yael Blankenheim, Julio Dávila-Valls, Paloma García-Clemente, Tomas Freiberger, Jochem Buil, Jacques F Meis, Deniz Akyol, Hélène Guegan, Clare Logan

a Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria 
b Translational Medical Mycology Research Unit, European Confederation of Medical Mycology Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria 
c BioTechMed, Graz, Austria 
d Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany 
e Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany 
f Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, and European Confederation of Medical Mycology Excellence Center for Medical Mycology, University of Cologne, Cologne, Germany 
g Centre for Molecular Medicine Cologne, University of Cologne, Cologne, Germany 
h Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany 
i Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), UMR_S 1085, Rennes, France 
j Institute of Infection and Immunity, St George’s University of London, London, UK 
k Department of Medical Microbiology, Hacettepe University Medical School, Ankara, Türkiye 
l Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Medical School, Ankara, Türkiye 
m Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain 
n Department of Clinical Mycology, Allergy and Immunology, North Western State Medical University, St Petersburg, Russia 
o Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 
p Medical Mycology Reference Laboratory, Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 
q Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden 
r Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden 
s Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden 
t Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, Netherlands 
u Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, Netherlands 
v Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands 
w Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland 
x Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy 
y Infectious Diseases Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 
z Mycology Reference Centre Manchester and Department of Infectious Diseases, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK 
aa Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK 
ab Laboratory of Clinical Microbiology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium 
ac Department of Laboratory Medicine and National Reference Center for Mycosis, UZ Leuven, Leuven, Belgium 
ad Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bursa Uludağ University, Bursa, Türkiye 
ae Centre for Microbiology, Institute of Public Health of Vojvodina, Novi Sad, Serbia 
af Northumbria Healthcare NHS Foundation Trust, North Shields, UK 
ag Laboratory of Parasitology and Mycology, Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France 
ah Department of Infectious Diseases, Hôpital Saint-Louis, Fernand Widal, Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France 
ai Paris Cité Université, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France 
aj Department of Infectious Diseases, Centre Hospitalier Universitaire de Strasbourg, Université de Strasbourg, Strasbourg, France 
ak Department of Hematology, Amsterdam University Medical Centers, Amsterdam, Netherlands 
al Department of Parasitology-Mycology-Tropical Medicine, Centre Hospitalier Régional Universitaire de Tours, Tours, France 
am Department of Oncohematology, Comenius University and National Cancer Institute, Bratislava, Slovakia 
an Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Türkiye 
ao Department of Internal Medicine, Infectious Diseases Unit, FondazioneIRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy 
ap Department of Pathophysiology and Transplantation and Centre for Multidisciplinary Research in Health Science (MACH), University of Milan, Milan, Italy 
aq Microbiology Department, La Paz University Hospital, Madrid, Spain 
ar Department of Infectious Diseases, Hospital Clínic de Barcelona, Barcelona, Spain 
as Department of Infection, Guy’s and St Thomas’ NHS Foundation Trust, London, UK 
at Medical Research Council Clinical Trials Unit, University College London, London, UK 
au Department of Microbiology, Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic 
av Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 
aw Laboratory of Clinical Microbiology and Molecular Biology, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal 
ax Institute of Hygiene and Medical Microbiology, European Confederation of Medical Mycology Excellence Center for Medical Mycology, Innsbruck Medical University, Innsbruck, Austria 
ay Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK 
az Institute of Medical Sciences, School of Medicine Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK 
ba Centre Hospitalier de Versailles, Hématologie, Le Chesnay, France 
bb Belfast Health and Social Care Trust, Belfast, UK 
bc Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 
bd Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK 
be Hospital Nuestra Señora de Sonsoles, Ávila, Spain 
bf Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, UK 
bg Unit of Infectious Diseases and Microbiology, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío, Seville, Spain 
bh Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Madrid, Spain 
bi Infectious Diseases Department, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece 
bj First Department of Medicine, Laikon General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece 
bk Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany 
bl Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Marmara University, Istanbul, Türkiye 
bm Department of Infectious Diseases and Clinical Microbiology, Ege University Medical School, Izmir, Türkiye 
bn Department of Microbiology, St Anne’s Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic 
bo Institute for Clinical Hygiene, Medical Microbiology and Infectiology, Paracelsus Medical University, Klinikum Nürnberg, Nuremberg, Germany 
bp Section of Infectious Diseases, Department of Medicine II, Justus-Liebig-University Giessen, Giessen, Germany 
bq Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Akdeniz University, Antalya, Türkiye 
br Division of Nephrology and Infectious Diseases, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium 
bs Microbiology Division, Public Health Wales, Cardiff, UK 
bt Centre for Trials Research and Division of Infection and Immunity, Cardiff University, Cardiff, UK 
bu Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria 
bv Department of Public Health, Microbiology, and Virology, Università degli Studi di Milano, Milan, Italy 
bw Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark 
bx Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark 
by Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 
bz German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany 

* Correspondence to: Prof Martin Hoenigl, Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria Division of Infectious Diseases Department of Internal Medicine Medical University of Graz Graz 8036 Austria

Summary

Background

The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes.

Methods

In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines.

Findings

632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04–1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05–1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4–30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals.

Interpretation

Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay.

Funding

Scynexis.

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