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European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study - 13/10/23

Doi : 10.1016/j.jinf.2023.08.001 
Maiken Cavling Arendrup a, b, c, , 1 , Sevtap Arikan-Akdagli d, 2, Karin Meinike Jørgensen a, Aleksandra Barac e, 3, Jörg Steinmann f, 4, Cristina Toscano g, Valentina Arsic Arsenijevic h, 5, Assunta Sartor i, 6, Cornelia Lass-Flörl j, 7, Axel Hamprecht k, l, 8, Tadeja Matos m, 9, Benedict R.S. Rogers n, 10, Inmaculada Quiles o, Jochem Buil p, q, r, 11, Volkan Özenci s, t, 12, Robert Krause u, v, Matteo Bassetti w, x, 13, Laura Loughlin y, 14, Blandine Denis z, Anna Grancini aa, P. Lewis White ab, 15, Katrien Lagrou ac, ad, 16, Birgit Willinger ae, Riina Rautemaa-Richardson af, ag, 17, Petr Hamal ah, 18, Beyza Ener ai, 19, Tugce Unalan-Altintop d, 20, Ebru Evren aj, 21, Suleyha Hilmioglu-Polat ak, 22, Yasemin Oz al, 23, Ozlem Koyuncu Ozyurt am, 24, Faruk Aydin an, 25, Filip Růžička ao, 26, Eelco F.J. Meijer p, q, r, 27, Jean Pierre Gangneux ap, 28, Deborah E.A. Lockhart aq, ar, 29, Nina Khanna as, 30, Clare Logan at, au, 31, Ulrike Scharmann av, 32, Guillaume Desoubeaux aw, 33, Emmanuel Roilides ax, 34, Alida Fe Talento ay, 35, Karin van Dijk az, 36, Philipp Koehler ba, bb, 37, Jon Salmanton-García ba, bb, 38, Oliver A. Cornely ba, bb, 39, Martin Hoenigl u, v, , 40
a Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark 
b Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark 
c Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 
d Department of Medical Microbiology, Hacettepe University Medical School, Ankara, Turkey 
e Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Belgrade, Serbia 
f Institute for Clincal Hygiene, Medical Microbiology and Infectiology, Paracelsus Medical University, Klinikum Nürnberg, Nuremberg, Germany 
g Microbiology Laboratory, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal 
h Faculty of Medicine University of Belgrade, Institute of Microbiology and Immunology, Medical Mycology Reference Laboratory (MMRL), Belgrade, Serbia 
i SC Microbiology, Department of Laboratory Medicine, Friuli Centrale University Health Authority, Udin, Italy 
j Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria 
k University of Cologne, University Hospital Cologne, Institute for Medical Microbiology, Immunology and Hygiene, Cologne, Germany 
l University of Oldenburg, Institute for Medical Microbiology and Virology, Oldenburg, Germany 
m Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Slovenia 
n Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom 
o Department of Microbiology, La Paz University Hospital, Madrid, Spain 
p Canisius Wilhelmina Hospital (CWZ), Medical Microbiology and Infectious Diseases, Nijmegen, the Netherlands 
q Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands 
r Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands 
s Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Sweden 
t Department of Clinical Microbiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden 
u Biotech Med, Graz, Austria 
v Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria 
w Infectious Diseases Unit, IRCCS San Martino Polyclinic Hospital, Genoa, Italy 
x Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy 
y Belfast Health and Social Care Trust, Belfast, United Kingdom 
z Department of Infectious Diseases, Hôpital Saint-Louis, Fernand Widal, Lariboisière, AP-HP, Paris, France 
aa U.O.S Microbiology – Analysis Laboratory, IRCCS Foundation, Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy 
ab Public Health Wales Microbiology Cardiff and Cardiff University School of Medicine, United Kingdom 
ac Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium 
ad Department of Laboratory Medicine and National Reference Center for Mycosis University Hospitals Leuven, Leuven, Belgium 
ae Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria 
af Mycology Reference Centre Manchester and Department of Infectious Diseases, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom 
ag Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, United Kingdom 
ah Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic 
ai Department of Medical Microbiology, Bursa Uludağ University Medical School, Bursa, Turkey 
aj Department of Medical Microbiology, Ankara University Medical School, Ankara, Turkey 
ak Department of Medical Microbiology, Ege University Medical School, Izmir, Turkey 
al Department of Medical Microbiology, Eskisehir Osmangazi University Medical School, Eskisehir, Turkey 
am Department of Medical Microbiology, Akdeniz University Medical School, Antalya, Turkey 
an KTÜ Tıp Fakültesi Tıbbi Mikrobiyoloji AbD, Trabzon, Turkey 
ao Masaryk University, Faculty of Medicine and St. Anne’s Faculty Hospital, Department of Microbiology, Brno, Czech Republic 
ap Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), UMR_S 1085, F-35000 Rennes, France 
aq Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, United Kingdom 
ar Institute of Medical Sciences, School of Medicine Medical Sciences & Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom 
as Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland 
at Clinical Infection Unit, St Georges University NHS Hospital Foundation Trust, Blackshaw Road, London, United Kingdom 
au Institute of Infection & Immunity, St Georges University London, Cranmer Terrace, London, United Kingdom 
av Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany 
aw Department of Parasitology-Mycology-Tropical medicine, CHRU Tours, Tours, France 
ax Hippokration General Hospital, Infectious Diseases Department, Medical School, Aristotle University of Thessaloniki, Greece 
ay Department of Microbiology, Beaumont Hospital, Dublin, Ireland 
az Department of Medical Microbiology and Infection Control, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands 
ba University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, and Excellence Center for Medical Mycology (ECMM), Cologne, Germany 
bb University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Institute of Translational Research, Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany 

Correspondence to: Statens Serum Institut, Artillerivej 5, Unit for Mycology (Building 45-112), DK-2300 Copenhagen S, Denmark.Statens Serum InstitutArtillerivej 5, Unit for Mycology (Building 45-112)Copenhagen SDK-2300Denmark⁎⁎Correspondence to: Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.Division of Infectious Diseases, Department of Internal Medicine, Medical University of GrazAuenbruggerplatz 15Graz8036Austria

Summary

The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25–33%) while Italy and Turkey had the highest C. parapsilosis proportions (24–26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.

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Highlights

Candidaemia epidemiology differs notably across 41 centres in 17 countries.
C. albicans proportions varied from 77% in Austria to 36% in Turkey.
Acquired fluconazole resistance emerges in C. parapsilosis in southern Europe.
A novel echinocandin resistance mutation and MDR was demonstrated in C. parapsilosis.
Antifungal stewardship and infection control is of utmost importance.

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Keywords : Candida, C. parapsilosis, Fluconazole resistance, Echinocandin resistance, Fks1, EUCAST


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Vol 87 - N° 5

P. 428-437 - novembre 2023 Retour au numéro
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