Association of antifungal treatment duration with 90-day mortality in critically ill adults with candidemia: a multicenter target trial emulation in France
Abstract
Background: The optimal duration of antifungal therapy for candidemia in intensive care unit (ICU) patients remains uncertain. We aimed to evaluate whether shorter antifungal therapy was not associated with increased mortality using a target trial emulation framework. Methods: We conducted a multicenter cohort study including adult ICU patients with candidemia from 16 ICUs in France (January 1, 2015 to January 1, 2023), emulating a target trial comparing short-course (<10 days) versus long-course (≥10 days) antifungal therapy. Patients treated for more than 21 days were excluded to minimize indication bias related to complicated candidemia. Patients who died within five days were excluded to ensure eligibility for both strategies. To account for time-dependent bias and confounding, we applied a cloning–censoring–weighting approach with inverse probability weighting. The primary outcome was all-cause mortality at day 90 after candidemia onset. Findings: Among 237 eligible patients with uncomplicated candidemia from the 492 enrolled in the CandidICU cohort, 48 (20.3%) received short-course and 189 (79.7%) long-course therapy. Overall 90-day mortality was 47.7% (113/237). Median age was 62 years [IQR 51–70], median SAPS II was 53 [40–68], and Candida albicans accounted for 66.7% of cases. After weighting, baseline characteristics were well balanced. Short-course therapy was not significantly associated with 90-day mortality (weighted HR 1.14, 95% CI 0.82–1.58). No differences were observed in secondary infections or organ support between groups. Interpretation: In this multicenter ICU cohort, among patients who survive the initial 5 days after candidemia onset and do not have obvious indication for prolonged therapy, short-course antifungal therapy was not associated with increased 90-day mortality after adjustment for time-dependent bias and confounders, although the confidence interval is wide and compatible with both clinically important benefit and harm. These findings are hypothesis-generating and should not alter current clinical practice. Randomized controlled trials are needed to definitively determine optimal treatment duration in critically ill patients.
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BibTeX
@article{reizine2026association,
title = {{Association of antifungal treatment duration with 90-day mortality in critically ill adults with candidemia: a multicenter target trial emulation in France}},
author = {Florian Reizine and Juliette Henry and Luc Desmedt and Christophe Camus and Jean-Marc Tadie and Valentin Coirier and François Arrivé and Estelle Burban and Gabriel Eustache and Tony Belleville and Antoine Marc and Jolan Malherbe and Pierre Bouju and Paul Jaubert and Olivier Lesieur and Maxime Leclerc and Pierre Fillâtre and Aurelien Frerou and Renaud Prevel and Nolwenn Mainguy and Anne Cady and Florent Morio and Solène Le Gal and Estelle Perraud and Laurence Delhaes and Sébastien Imbert and Hélène Guegan and Julie Bonhomme and Marc Pihet and Clarisse Dupin and Benjamin Gaborit and Agathe Delbove and Damien Du Cheyron and Yoann Launey and Cécile Aubron and Jean-Pierre Gangneux},
journal = {EClinicalMedicine},
year = {2026},
month = sep,
doi = {10.1016/j.eclinm.2026.104178},
url = {https://hal.science/hal-05750127v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Association of antifungal treatment duration with 90-day mortality in critically ill adults with candidemia: a multicenter target trial emulation in France
AU - Florian Reizine
AU - Juliette Henry
AU - Luc Desmedt
AU - Christophe Camus
AU - Jean-Marc Tadie
AU - Valentin Coirier
AU - François Arrivé
AU - Estelle Burban
AU - Gabriel Eustache
AU - Tony Belleville
AU - Antoine Marc
AU - Jolan Malherbe
AU - Pierre Bouju
AU - Paul Jaubert
AU - Olivier Lesieur
AU - Maxime Leclerc
AU - Pierre Fillâtre
AU - Aurelien Frerou
AU - Renaud Prevel
AU - Nolwenn Mainguy
AU - Anne Cady
AU - Florent Morio
AU - Solène Le Gal
AU - Estelle Perraud
AU - Laurence Delhaes
AU - Sébastien Imbert
AU - Hélène Guegan
AU - Julie Bonhomme
AU - Marc Pihet
AU - Clarisse Dupin
AU - Benjamin Gaborit
AU - Agathe Delbove
AU - Damien Du Cheyron
AU - Yoann Launey
AU - Cécile Aubron
AU - Jean-Pierre Gangneux
PY - 2026
DA - 2026/09/05
JO - EClinicalMedicine
DO - 10.1016/j.eclinm.2026.104178
UR - https://hal.science/hal-05750127v1
AB - Background: The optimal duration of antifungal therapy for candidemia in intensive care unit (ICU) patients remains uncertain. We aimed to evaluate whether shorter antifungal therapy was not associated with increased mortality using a target trial emulation framework. Methods: We conducted a multicenter cohort study including adult ICU patients with candidemia from 16 ICUs in France (January 1, 2015 to January 1, 2023), emulating a target trial comparing short-course (<10 days) versus long-course (≥10 days) antifungal therapy. Patients treated for more than 21 days were excluded to minimize indication bias related to complicated candidemia. Patients who died within five days were excluded to ensure eligibility for both strategies. To account for time-dependent bias and confounding, we applied a cloning–censoring–weighting approach with inverse probability weighting. The primary outcome was all-cause mortality at day 90 after candidemia onset. Findings: Among 237 eligible patients with uncomplicated candidemia from the 492 enrolled in the CandidICU cohort, 48 (20.3%) received short-course and 189 (79.7%) long-course therapy. Overall 90-day mortality was 47.7% (113/237). Median age was 62 years [IQR 51–70], median SAPS II was 53 [40–68], and Candida albicans accounted for 66.7% of cases. After weighting, baseline characteristics were well balanced. Short-course therapy was not significantly associated with 90-day mortality (weighted HR 1.14, 95% CI 0.82–1.58). No differences were observed in secondary infections or organ support between groups. Interpretation: In this multicenter ICU cohort, among patients who survive the initial 5 days after candidemia onset and do not have obvious indication for prolonged therapy, short-course antifungal therapy was not associated with increased 90-day mortality after adjustment for time-dependent bias and confounders, although the confidence interval is wide and compatible with both clinically important benefit and harm. These findings are hypothesis-generating and should not alter current clinical practice. Randomized controlled trials are needed to definitively determine optimal treatment duration in critically ill patients.
SN - 2589-5370
ER -