Attributable mortality of candidemia – Results from the ECMM Candida III multinational European Observational Cohort Study - 10/08/24

Doi : 10.1016/j.jinf.2024.106229

Jon Salmanton-García ^a,^b,^c, Oliver A. Cornely ^a,^b,^c,^d,^⁎ , Jannik Stemler ^a,^b, Aleksandra Barać ^e, Jörg Steinmann ^f, Alena Siváková ^g, Emin Halis Akalin ^h, Sevtap Arikan-Akdagli ⁱ, Laura Loughlin ^j, Cristina Toscano ^k, Manjusha Narayanan ^l, Benedict Rogers ^m, Birgit Willinger ⁿ, Deniz Akyol ^o, Emmanuel Roilides ^p, Katrien Lagrou ^q, Malgorzata Mikulska ^r, Blandine Denis ^s, Diane Ponscarme ^t, Urlike Scharmann ^u, Alpay Azap ^v, Deborah Lockhart ^w,^x, Tihana Bicanic ^y, Florian Kron ^z,^aa,^ab,^ac, Nurettin Erben ^ad, Riina Rautemaa-Richardson ^ae, Anna L. Goodman ^af, Carolina Garcia-Vidal ^ag, Cornelia Lass-Flörl ^ah, Jean-Pierre Gangneux ^ai, Lucia Taramasso ^aj, Maite Ruiz ^ak,^al,^am, Yael Schick ^a,^b, Eric Van Wijngaerden ^q, Christopher Milacek ⁿ, Daniele Roberto Giacobbe ^r, Clare Logan ^y, Emily Rooney ^an, Andrea Gori ^aj, Murat Akova ^ao, Matteo Bassetti ^r, Martin Hoenigl ^ap,^aq,^ar,^⁎,^{^{1
Shared senior authors.}} , Philipp Koehler ^a,^b,^c,^{^{1
Shared senior authors.}}
^a University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
^b University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany
^c German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
^d Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
^e Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
^f Institute for Clinical Hygiene and Medical Microbiology, Paracelsus Medical University, Nuremberg, Germany
^g Department of Microbiology, St Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
^h Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bursa Uludağ University, Bursa, Turkey
ⁱ Department of Medical Microbiology, Hacettepe University Medical School, Ankara, Turkey
^j Belfast Health and Social Care Trust, Belfast, United Kingdom
^k Laboratory of Clinical Microbiology and Molecular Biology, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal
^l Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
^m Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
ⁿ Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
^o Ege Univerisity Infectious Diseases and Clinical Microbiology, Izmir, Turkey
^p Infectious Diseases Department, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
^q Laboratory of Clinical Microbiology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
^r IRCCS Ospedale Policlinico San Martino di Genova, Genoa, Italy
^s Department of Infectious Diseases, Hôpital Saint-Louis, Fernand Widal, Lariboisière, AP-HP, 1 Avenue Claude Vellefaux, 75010 Paris, France
^t Saint Louis Hospital, Paris, France
^u Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
^v Ankara University, IDCM, Ankara, Turkey
^w Institute of Medical Sciences, School of Medicine Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
^x Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK, School of Medicine Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
^y Clinical Academic Group in Infection and Immunity, St. George’s University Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
^z VITIS Healthcare Group, Cologne, Germany
^aa Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
^ab Center for Integrated Oncology (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
^ac FOM University of Applied Sciences, Essen, Germany
^ad Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
^ae Mycology Reference Centre Manchester, ECMM Centre of Excellence, and Department of Infectious Diseases, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
^af Department of Infectious Diseases, Centre for Clinical Infection and Diagnostics Research (CIDR), Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London, and Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom
^ag Department of Infectious Diseases, Hospital Clínic de Barcelona, Barcelona, Spain
^ah Institute of Hygiene and Medical Microbiology, European Confederation of Medical Mycology Excellence Center for Medical Mycology, Innsbruck Medical University, Innsbruck, Austria
^ai University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), UMR_S 1085, Rennes, France
^aj Departement of Internal Medicine Fondazione IRCCS Cà Granda Osepdale Maggiore Policlinico, Milan, Italy
^ak UGC Enfermedades Infecciosas, Microbiología y Parasitología, University Hospital Virgen del Rocío, Seville, Spain
^al Grupo Microbiología Clínica y Molecular, Instituto de Biomedicina de Sevilla, HUVR/CSIC/Universidad de Sevilla, Seville, Spain
^am Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Madrid, Spain
^an Department of Infectious Diseases, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
^ao Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Medical School, Ankara, Turkey
^ap Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria
^aq Translational Medical Mycology Research Unit, European Confederation of Medical Mycology Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria
^ar BioTechMed, Graz, Austria

^⁎Correspondence to: University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), and University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Herderstraße 52-54, 50931 Cologne, Germany.University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), and University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM)Herderstraße 52-54Cologne50931Germany^⁎⁎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

Introduction

Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections.

Methods

In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed.

Results

One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10–33) vs 15 days (IQR 7–28); p = 0.004).

Conclusions

Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality.

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Highlights

•	Candidemia remains a significant challenge with a mortality rate of 40.4%.
•	Non-albicans Candida species show higher resistance rates to antifungals.
•	Attributable mortality in candidemia is 18.2%, emphasizing its impact on patient outcomes.
•	Candida tropicalis exhibits the highest species-specific mortality at 63.6%.
•	ICU admission is major risk factor associated with candidemia mortality.

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Keywords : Candidaemia, Mortality, Epidemiology, Risk factors, Candida, Hospitalization

Plan

Introduction

Methods

Results

Case-control analysis

Attributable mortality depending on causative Candida spp

Analysis of treatment strategies and characteristics of survivors vs.non-survivor of candidemia

Discussion

Funding

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Vol 89 - N° 3

Article 106229- septembre 2024 Retour au numéro

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Attributable mortality of candidemia – Results from the ECMM Candida III multinational European Observational Cohort Study - 10/08/24

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