Decoding candidemia in critically ill patients: unsupervised clustering identifies three unique phenotypes

BACKGROUND: Candidemia displays significant clinical heterogeneity in critically ill patients. This study aimed to identify distinct clinical phenotypes and to assess their association with 90-day mortality. METHODS: We conducted a multicenter retrospective cohort study of 492 intensive care unit (ICU) patients with candidemia from 16 French ICUs (2015-2023). We performed a factor analysis of mixed data (FAMD) incorporating both categorical and continuous baseline variables, followed by hierarchical clustering on principal components (HCPC). Survival analysis was performed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Overall, 90-day mortality for the 492 patients (median age: 64 years, 69.1% male) with candidemia was 62.6%. Three different phenotypes emerged from FAMD followed by HCPC: Phenotype 1 (n = 70, 14.2%) comprised patients with severe immunosuppression, mostly due to hematological malignancies (82.9%), and high severity scores (SAPS II:70); Phenotype 2 (n = 223, 45.3%) corresponded to elderly cirrhotic patients (19.3%) with early-onset digestive candidemia; Phenotype 3 (n = 199, 40.5%) comprised younger patients with lower severity scores and catheter-related candidemia. Mortality differed significantly between phenotypes: 72.9% (Phenotype 1), 70.4% (Phenotype 2), and 50.3% (Phenotype 3) (p < 0.001). Independent predictors of mortality included age (aHR: 1.01, 95% CI: 1.00-1.02; p = 0.003), cirrhosis (aHR: 1.90, 95% CI: 1.39-2.60; p < 0.001), SAPS II (aHR: 1.01, 95% CI: 1.01-1.02; p < 0.001), echinocandin use (aHR = 0.49, 95% CI: 0.39-0.63; p < 0.001) and proven catheter-related candidemia (protective; aHR: 0.48, 95% CI: 0.33-0.69; p < 0.001). Immunodepression was not associated with mortality. CONCLUSION: Unsupervised clustering identified three clinically different candidemia phenotypes with different outcomes. Cirrhosis, higher age and illness severity were associated with mortality, whereas a catheter-related source of infection was protective.

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Journal
Critical Care
Published
2026-06-28
DOI
https://doi.org/10.1186/s13054-026-05964-4
Primary Topic
Blood disorders and treatments
Type
article
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article

Decoding candidemia in critically ill patients: unsupervised clustering identifies three unique phenotypes

Clarisse Dupin, Sébastien Imbert, Maxime Leclerc, Marc Pihet et al.
Critical Care
Blood disorders and treatments
article

Decoding candidemia in critically ill patients: unsupervised clustering identifies three unique phenotypes

Clarisse Dupin, Sébastien Imbert, Maxime Leclerc, Marc Pihet, Hélène Guegan, Julie Bonhomme, Olivier Lesieur, Nolwenn Mainguy, Jean‐Pierre Gangneux, Cécile Aubron, Juliette Henry, Paul Jaubert, Jolan Malherbe, Aurélien Frerou, Solène Le Gal, Gabriel Eustache, Luc Desmedt, Anne Cady, François Arrivé, Laurence Delhaès, Valentin Coirier, Renaud Prével, Damien du Cheyron, Florent Morio, Estelle Perraud, Pierre Fillâtre, Antoine Marc, Estelle Burban, Tony Belleville, Pierre Bouju, Christophe Camus, Yoann Launey, Florian Reizine, Agathe Delbove
article en

Abstract

BACKGROUND: Candidemia displays significant clinical heterogeneity in critically ill patients. This study aimed to identify distinct clinical phenotypes and to assess their association with 90-day mortality. METHODS: We conducted a multicenter retrospective cohort study of 492 intensive care unit (ICU) patients with candidemia from 16 French ICUs (2015-2023). We performed a factor analysis of mixed data (FAMD) incorporating both categorical and continuous baseline variables, followed by hierarchical clustering on principal components (HCPC). Survival analysis was performed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Overall, 90-day mortality for the 492 patients (median age: 64 years, 69.1% male) with candidemia was 62.6%. Three different phenotypes emerged from FAMD followed by HCPC: Phenotype 1 (n = 70, 14.2%) comprised patients with severe immunosuppression, mostly due to hematological malignancies (82.9%), and high severity scores (SAPS II:70); Phenotype 2 (n = 223, 45.3%) corresponded to elderly cirrhotic patients (19.3%) with early-onset digestive candidemia; Phenotype 3 (n = 199, 40.5%) comprised younger patients with lower severity scores and catheter-related candidemia. Mortality differed significantly between phenotypes: 72.9% (Phenotype 1), 70.4% (Phenotype 2), and 50.3% (Phenotype 3) (p < 0.001). Independent predictors of mortality included age (aHR: 1.01, 95% CI: 1.00-1.02; p = 0.003), cirrhosis (aHR: 1.90, 95% CI: 1.39-2.60; p < 0.001), SAPS II (aHR: 1.01, 95% CI: 1.01-1.02; p < 0.001), echinocandin use (aHR = 0.49, 95% CI: 0.39-0.63; p < 0.001) and proven catheter-related candidemia (protective; aHR: 0.48, 95% CI: 0.33-0.69; p < 0.001). Immunodepression was not associated with mortality. CONCLUSION: Unsupervised clustering identified three clinically different candidemia phenotypes with different outcomes. Cirrhosis, higher age and illness severity were associated with mortality, whereas a catheter-related source of infection was protective.

Critical Care
Université de Bordeaux (FR), Inserm (FR), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Nantes (FR), Université de Poitiers (FR), Centre Hospitalier de Bretagne Sud (FR), Centre Hospitalier de Saint-Brieuc (FR), Bordeaux Population Health (FR), Institut de Recherche en Santé, Environnement et Travail (FR), Centre hospitalier Bretagne Atlantique (FR), Centre Hospitalier Universitaire de Poitiers (FR), Laboratoire National de Référence (MA), Centre Hospitalier Universitaire d'Angers (FR), Centre Hospitalier de Saint-Malo (FR), Centre Hospitalier Régional Universitaire de Brest (FR), Centre Hospitalier de La Rochelle (FR), Centre Hospitalier Départemental Vendée (FR), Centre Hospitalier Universitaire de Rennes (FR), Université d'Angers (FR), Université de Rennes (FR), Imation (United States) (US), Nantes Université (FR), Université de Caen Normandie (FR)
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Blood disorders and treatments
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