European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study.

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.

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Declaration of Competing Interest Outside this work the authors have the following potential conflicts to declare: MaCA has received research grants/contract work (paid to the SSI) from Amplyx, Basilea, Cidara, F2G, Gilead, Novabiotics and Scynexis, and speaker honoraria (personal fee) from Astellas, Chiesi, Gilead, MSD, and SEGES over the past 5 years. She is the current chairman of the EUCAST-AFST. SAA reports research grant from Cidara, lecture honoraria from Gilead, and travel grant from Astellas. MH reports research funding from Astellas, Gilead, MSD, Pfizer, Euroimmun, and Scynexis. PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. JSG reports speaker honoraria from Gilead and Pfizer outside of the submitted work. OAC reports grants or contracts from Amplyx, Basilea, Cidara, F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pardes, Pfizer, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Abbvie, Al-Jazeera Pharmaceuticals/Hikma, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, MedScape, MedUpdate, MSD, Mylan, Noscendo, Pfizer, Shionogi; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board of Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, The Prime Meridian Group; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7). CLF has received research grants from Pfizer, Basilea, F2G, Gilead, and Scynexis, and speaker honoraria from Gilead, MSD, and Pfizer over the past 5 years. RK received research grants from Merck and Pfizer and served on the speakers’ bureau of Pfizer, Gilead, Astellas, Basilea, Merck, Angelini, and Shionogi. GD has received lecture honoraria from Gilead and Pfizer, outside of the submitted work. He was also invited to symposia and congresses by the two aforementioned companies. AFT has received grants and speaker honoraria from Pfizer and Gilead outside of this work. PLW performed diagnostic evaluations and received meeting sponsorship from Bruker, Dynamiker, and Launch Diagnostics; Speakers fees, expert advice fees and meeting sponsorship from Gilead; Speaker and expert advice fees from F2G and speaker fees MSD and Pfizer: Speakers fees and performed diagnostic evaluations for Associates of Cape Cod and IMMY. JPG has received lecture honoraria from Gilead, MundiPharma and Pfizer. NK is a member of the Gilead, Merck Sharp & Dohme AG (MSD) and Pfizer advisory boards for invasive fungal infections, chair of the DSMB of Pulmicide, and reports grants from The Swiss National Science Foundation (grant number 32003B_204944 and the National Centre of Competence in Research AntiResist Grant 51NF40_180541), outside the submitted work. ER reports grants to his institutions from Astellas, MSD, Scynexis, Shionogi, GSK, Pfizer, Gilead and Allergan. He has served as consultant to Amplyx, Astellas, Gilead, MSD, Pfizer, Scynexis, GSK and Shionogi. CL reports conference sponsorship from Gilead Sciences. BD reports consulting fees from Gilead, Pfizer and travel grant from Gilead. KL received consultancy fees from MRM Health, MSD and Gilead, speaker fees from FUJIFILM WAKO, Pfizer and Gilead and a service fee from Thermo fisher Scientific and TECOmedical. MB reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Bayer, BioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, and Shionogi. VÖ reports research funding and/or collaborations with Abbott, Accelerate diagnostics, Astrego AB, Becton, Dickinson and Company (BD), BioFire Diagnostics, bioMérieux, Bruker, Nittobo Medical Co, QuantaMatrix, Quidel, SD Biosensor, SSI Diagnostica, and T2 Biosystems. BW reports research grant from Pfizer and Schülke & Mayr, advisory board for Merck Sharp & Dohme and Pfizer and speaker honoraria from Gilead, Pfizer, bioMerieux, Euro Immun, CapeCod, Immy and Diasorin. VAA reports research funding from Pfizer. JS has received lecture honoraria from Gilead and Pfizer, outside of the submitted work. JBB has received research grants from F2G and Gilead outside of the submitted work. The following authors had no potential conflicts to declare: Tadeja Matos, Eelco F.J. Meijer, Beyza Ener, Ebru EVREN, Laura Loughlin, Riina Rautemaa-Richardson, Suleyha Hilmioglu-Polat, Deborah E. A. Lockhart, Benedict R.S. Rogers, Ulrike Scharmann, Filip Růžička, Axel Hamprecht, Karin Van Dijk, Anna Grancini, Petr Hamal, Tuğçe Ünalan-Altıntop, Yasemin OZ, Aleksandra Barac, Assunta SARTOR, Faruk Aydin, Özlem Koyuncu Özyurt.