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.