Early adequate empiric antifungal therapy and 28-day mortality in ICU patients with candidemia: a pooled patient-level analysis of EUROBACT-1 and EUROBACT-2 cohorts

Abstract Background The optimal timing of empiric antifungal therapy in patients with suspected candidemia remains uncertain. In practice, many antifungal treatments initiated empirically are eventually found to be unnecessary, exposing patients to potential toxicity, selection of non- albicans Candida species, emergence of resistance, and additional costs. The objective of the study was to evaluate whether adequate empiric antifungal therapy initiated within 2 days after blood culture draw was associated with 28-day mortality. Methods We performed a pooled secondary analysis of two prospective worldwide observational cohorts (EUROBACT-1 and EUROBACT-2) including adult patients with Candida bloodstream infection. The exposure was defined as receipt of adequate antifungal therapy within 2 days after blood culture draw. Propensity scores for receiving early adequate antifungal therapy were estimated using prespecified covariates, and inverse probability of treatment weights were applied in a weighted Cox proportional hazards model to assess the association with 28-day mortality. Prespecified subgroup analyses were conducted according to study cohort, Candida species, and presence of hypotension at the time of bloodstream infection. As a sensitivity analysis, a frailty Cox proportional hazards model including a random center effect was performed. Results The final study population included 272 patients with candidemia from 158 centers, including 81 from EUROBACT-1 and 191 from EUROBACT-2. One hundred and ten patients received early adequate antifungal therapy and 162 did not. Overall, 38.6% of patients (105/272) died within 28 days, including 40.9% (45/110) in the early adequate therapy group and 37.0% (60/162) in the non-early adequate therapy group. In the weighted Cox model, early adequate antifungal therapy was not significantly associated with 28-day mortality (HR 1.23, 95% CI 0.82–1.83, p = 0.314). Results were consistent across subgroup analyses according to study cohort, Candida species, the presence of hypotension at the time of bloodstream infection, as well as in the frailty Cox sensitivity analysis. Conclusions Early adequate antifungal therapy was not independently associated with improved 28-day survival in ICU patients with candidemia. These findings support a more targeted approach to early empirical antifungal treatment and underscore the need to identify patient subgroups most likely to benefit from immediate therapy.

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Journal
Critical Care
Published
2026-10-16
DOI
https://doi.org/10.1186/s13054-026-06373-3
Primary Topic
Antifungal resistance and susceptibility
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article
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article

Early adequate empiric antifungal therapy and 28-day mortality in ICU patients with candidemia: a pooled patient-level analysis of EUROBACT-1 and EUROBACT-2 cohorts

Fadi Ali, Laurent Argaud, Elli Antypa, R. Rao Baikady et al.
Critical Care
Antifungal resistance and susceptibility
article

Early adequate empiric antifungal therapy and 28-day mortality in ICU patients with candidemia: a pooled patient-level analysis of EUROBACT-1 and EUROBACT-2 cohorts

Fadi Ali, Laurent Argaud, Elli Antypa, R. Rao Baikady, Adel Mohamed Yasin Alsisi, Ahmed Aqeelah, David Benjamin Antcliffe, Fereshteh Amiri, Stuart Baker, Abdullah Khudhur Ahmed, Esra Aykaç, Alexis Tabah, Baurzhan Babashev, José Artur Paiva, Sabahat Cagan Aktas, Joaquin Amador Amerigo, Supriya Antrolikar, Kaori Atobe, A Armaganidis, Fayez Abilama, Abd. Hamid Azman, Johann Auchabie, Massimo M. Antonelli, Amer Aldhalia, Tayfun Adanır, Kostoula Arvaniti, Sarah Amro, Türkay Akbaş, Matteo Bassetti, Adrian Davalos-Alvarez, M. J. Asensio, Ben Attwood, Irene Alonzo, Ahmed Khaled Awad, Sonia Sousa Arias, Hannah Wozniak, Dorota Banach, Eleni Antoniadou, Zoi Athanasa, José Oscar Acevedo, Murat Akova, Eman Ali Abdulwahed, Jean‐François Timsit, Fatemeh Aalinezhad, Heleen Aardema, Nilgün Altın, Reza Baghbanian, Antony George Attokaran, Manan Bajaj, François Barbier, Özlem Akdoğan, Djillali Annane, Firdevs Aksoy, Fekri Abroug, Gaëtan Badre, Candy Garcia Aguilar, Ahmet Akyol, Maher Awad, Niccolò Buetti, Yutthana Apichatbutr, Bushray Alhadi Almiqlash, Élie Azoulay, Ghaleb A. Almekhlafi, Serge Alfandari, Neriman Defne Altıntaş, Nerea López de Arbina, Christelle Aparicio, Mariota Panagiota Almiroudi, Joyce Åkerlund, Fathi A. Abousnina, Lubna Bakr, Saedah Ali, Gabriel Asiyanbi, Hollie Angell, Canan Agalar, Sailaja K. Baby, Anastasia Anderzhanova, Sylvain Anselme, Fatemeh Ahmadi, Madalena Alves, Abdullah Tarık Aslan, Nadia Baig, Fowotade Adeola, Stéphane Ruckly, Samia Ayed, Marta Aparicio, María Pilar Gracia Arnillas, Charlotte Arbelot, Ahmed Aljabbary, Arvind Kumar Baronia, Halis AKALIN, Georgios Anthopoulos, Samiul Ahmed, Fernando Armestar, Kevin Laupland, J. Ignacio Ayestaran, Almajdoub Ali Mohammed Ali, EUROBACT-1 Study Group, I. Ozkan Akinci
article en

Abstract

Abstract Background The optimal timing of empiric antifungal therapy in patients with suspected candidemia remains uncertain. In practice, many antifungal treatments initiated empirically are eventually found to be unnecessary, exposing patients to potential toxicity, selection of non- albicans Candida species, emergence of resistance, and additional costs. The objective of the study was to evaluate whether adequate empiric antifungal therapy initiated within 2 days after blood culture draw was associated with 28-day mortality. Methods We performed a pooled secondary analysis of two prospective worldwide observational cohorts (EUROBACT-1 and EUROBACT-2) including adult patients with Candida bloodstream infection. The exposure was defined as receipt of adequate antifungal therapy within 2 days after blood culture draw. Propensity scores for receiving early adequate antifungal therapy were estimated using prespecified covariates, and inverse probability of treatment weights were applied in a weighted Cox proportional hazards model to assess the association with 28-day mortality. Prespecified subgroup analyses were conducted according to study cohort, Candida species, and presence of hypotension at the time of bloodstream infection. As a sensitivity analysis, a frailty Cox proportional hazards model including a random center effect was performed. Results The final study population included 272 patients with candidemia from 158 centers, including 81 from EUROBACT-1 and 191 from EUROBACT-2. One hundred and ten patients received early adequate antifungal therapy and 162 did not. Overall, 38.6% of patients (105/272) died within 28 days, including 40.9% (45/110) in the early adequate therapy group and 37.0% (60/162) in the non-early adequate therapy group. In the weighted Cox model, early adequate antifungal therapy was not significantly associated with 28-day mortality (HR 1.23, 95% CI 0.82–1.83, p = 0.314). Results were consistent across subgroup analyses according to study cohort, Candida species, the presence of hypotension at the time of bloodstream infection, as well as in the frailty Cox sensitivity analysis. Conclusions Early adequate antifungal therapy was not independently associated with improved 28-day survival in ICU patients with candidemia. These findings support a more targeted approach to early empirical antifungal treatment and underscore the need to identify patient subgroups most likely to benefit from immediate therapy.

Critical Care
Université de Tours (FR), University of Geneva (CH), Inserm (FR), Queensland University of Technology (AU), The University of Queensland (AU), Royal Brisbane and Women's Hospital (AU), Hospital de São João (PT), Assistance Publique – Hôpitaux de Paris (FR), Clinical Investigation Center Plurithematic Tours (FR), World Health Organization (CH), University Hospital of Geneva (CH), Centre hospitalier universitaire d'Orléans (FR), Hôpital Bichat-Claude-Bernard (FR), Ospedale Policlinico San Martino (IT), Redcliffe Hospital (AU), Centro Hospitalar do Porto (PT), Infection, Anti-microbiens, Modélisation, Evolution (FR), University of Genoa (IT)
Good health and well-being
Openalex Percentile: Top 12%
Antifungal resistance and susceptibility
DOIOpen Access PDFOpenAlex
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