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Cited by 133Antifungal resistance and susceptibilityInfective Endocarditis Diagnosis and ManagementFungal Infections and Studies

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Attributable mortality of candidemia – Results from the ECMM Candida III multinational European Observational Cohort Study

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Salmanton-García, Jon, Cornely, Oliver A., Stemler, Jannik, Barać, Aleksandra, Steinmann, Jörg, Siváková, Alena, Akalin, Emin Halis, Arikan-Akdagli, Sevtap, Loughlin, Laura, Toscano, Cristina, Narayanan, Manjusha, Rogers, Benedict, Willinger, Birgit, Akyol, Deniz, Roilides, Emmanuel, Lagrou, Katrien, Mikulska, Malgorzata, Denis, Blandine, Ponscarme, Diane, Scharmann, Urlike, Azap, Alpay, Lockhart, Deborah, Bicanic, Tihana, Kron, Florian, Erben, Nurettin, Rautemaa-Richardson, Riina, Goodman, Anna L., Garcia-Vidal, Carolina, Lass-Flörl, Cornelia, Gangneux, Jean-Pierre, Taramasso, Lucia, Ruiz, Maite, Schick, Yael, Van Wijngaerden, Eric, Milacek, Christopher, Giacobbe, Daniele Roberto, Logan, Clare, Rooney, Emily, Gori, Andrea, Akova, Murat, Bassetti, Matteo, Hoenigl, Martin, Koehler, Philipp·2024·Journal of Infection
DOI 10.1016/j.jinf.2024.106229
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Abstract

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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Image 1
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Fig. 1 Participating European countries. Dark blue represents countries that are part of both the ECMM Candida III study and the case-control analysis: the analysis included documented cases and controls from the following countries: United Kingdom (n = 37 case-control pairs), Turkey (n = 34 case-control pairs), Germany (n = 29 case-control pairs), Serbia (n = 13 case-control pairs), Czech Republic (n = 10, case-control pairs), Austria, Italy and Portugal (n = 8 case-control pairs each), Belgium, France, and Greece (n = 7, casecontrol pairs each), and Spain (n = 3 case-control pairs). Light blue represents countries involved in the ECMM Candida III study but not in the case-control analysis: Belarus, Ireland, Netherlands, Russia, Slovakia, Sweden, and Switzerland.
Fig. 1 Participating European countries. Dark blue represents countries that are part of both the ECMM Candida III study and the case-control analysis: the analysis included documented cases and controls from the following countries: United Kingdom (n = 37 case-control pairs), Turkey (n = 34 case-control pairs), Germany (n = 29 case-control pairs), Serbia (n = 13 case-control pairs), Czech Republic (n = 10, case-control pairs), Austria, Italy and Portugal (n = 8 case-control pairs each), Belgium, France, and Greece (n = 7, casecontrol pairs each), and Spain (n = 3 case-control pairs). Light blue represents countries involved in the ECMM Candida III study but not in the case-control analysis: Belarus, Ireland, Netherlands, Russia, Slovakia, Sweden, and Switzerland.CC-BY · From the PDF
Fig. 2 CONSORT diagram on study enrollment.
Fig. 2 CONSORT diagram on study enrollment.CC-BY · From the PDF
Fig. 3 Kaplan Meier survival curves for candidemia patients versus control patients. a) Survival probability in candidemia versus control patients. Sensitivity analysis is provided in Supplementary figure 1a. b) Candidemia survival probability according to species. Sensitivity analysis is provided in Supplementary figure 1b. c) Survival probability in Candida albicans candidemia and matched controls. Sensitivity analysis is provided in Supplementary figure 1c. d) Survival probability in Candida glabrata/ Nakaseomyces glabratus candidemia and matched controls. Sensitivity analysis is provided in Supplementary figure 1d. e) Survival probability in Candida parapsilosis candidemia and matched controls. Sensitivity analysis is provided in Supplementary figure 1e. f) Survival probability in Candida tropicalis candidemia and matched con­ trols. Sensitivity analysis is provided in Supplementary figure 1f.
Fig. 3 Kaplan Meier survival curves for candidemia patients versus control patients. a) Survival probability in candidemia versus control patients. Sensitivity analysis is provided in Supplementary figure 1a. b) Candidemia survival probability according to species. Sensitivity analysis is provided in Supplementary figure 1b. c) Survival probability in Candida albicans candidemia and matched controls. Sensitivity analysis is provided in Supplementary figure 1c. d) Survival probability in Candida glabrata/ Nakaseomyces glabratus candidemia and matched controls. Sensitivity analysis is provided in Supplementary figure 1d. e) Survival probability in Candida parapsilosis candidemia and matched controls. Sensitivity analysis is provided in Supplementary figure 1e. f) Survival probability in Candida tropicalis candidemia and matched con­ trols. Sensitivity analysis is provided in Supplementary figure 1f.CC-BY · From the PDF
Fig. 3 ( continued )
Fig. 3 ( continued )CC-BY · From the PDF
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Image 7
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  1. Vena, 2024, Laboratory and clinical management capacity for invasive fungal infections: the Italian landscape, Infection, 52, 197, 10.1007/s15010-023-02084-x · DOI

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Metadata

Authors
Salmanton-García, J., Cornely, O. A., Stemler, J., Barać, A., Steinmann, J., Siváková, A., Akalin, E. H., Arikan-Akdagli, S., Loughlin, L., Toscano, C., Narayanan, M., Rogers, B., Willinger, B., Akyol, D., Roilides, E., Lagrou, K., Mikulska, M., Denis, B., Ponscarme, D., Scharmann, U., Azap, A., Lockhart, D., Bicanic, T., Kron, F., Erben, N., Rautemaa-Richardson, R., Goodman, A. L., Garcia-Vidal, C., Lass-Flörl, C., Gangneux, J.-P., Taramasso, L., Ruiz, M., Schick, Y., Van Wijngaerden, E., Milacek, C., Giacobbe, D. R., Logan, C., Rooney, E., Gori, A., Akova, M., Bassetti, M., Hoenigl, M., & Koehler, P.
Affiliations
  • University of Cologne (DE)
  • Paracelsus Medizinische Privatuniversität (DE)
  • Masaryk University (CZ)
  • Belfast Health and Social Care Trust (GB)
  • Hospital de Egas Moniz (PT)
  • Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
  • University Hospitals of Leicester NHS Trust (GB)
  • Medical University of Vienna (AT)
  • Ege University (TR)
  • Aristotle University of Thessaloniki (GR)
  • KU Leuven (BE)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Hôpital Saint-Louis (FR)
  • Essen University Hospital (DE)
  • Ankara University (TR)
  • University of Aberdeen (GB)
  • National Health Service (GB)
  • Eskişehir Osmangazi University (TR)
  • Inserm (FR)
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
  • Ospedale Policlinico San Martino (IT)
  • Manchester University NHS Foundation Trust (GB)
  • Hacettepe University (TR)
  • Medical University of Graz (AT)
Corresponding author
  • Cornely, Oliver A.
  • Hoenigl, Martin
ORCID
Venue
Journal of Infection
Publisher
Elsevier BV
Published
2024-09
Volume
89
Issue
3
Pages
106229
ISSN
0163-4453 (ISSN-L)
DOI
10.1016/j.jinf.2024.106229
OpenAlex
W4400673495
Cited by
127
References
43
Citations by year
2026: 61 · 2025: 61 · 2024: 5
FWCI
44.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Infection (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, cc-by)
  • St George's Online Research Archive (St George's University of London) (submittedVersion)
  • Bursa Uludag University - AVESIS (submittedVersion)
  • HAL (submittedVersion, cc-by)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • National Institute for Health and Care Research (NIHR 203308)
  • Manchester Biomedical Research Centre (NIHR 203308)
  • Medical Research Council (MC_UU_00004/05)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Infective Endocarditis Diagnosis and Management
  • Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
Keywords
candidemia, attributable mortality, Candida species, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, risk factors, central venous catheters, total parenteral nutrition, kidney disease, ICU length of stay, antifungal therapy
MeSH terms
Adult, Aged, Aged, 80 and over, Antifungal Agents, Candida, Europe, Female, Humans, Male, Middle Aged, Risk Factors, Cohort Studies, Case-Control Studies, Candidemia

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