Association of antifungal treatment duration with 90-day mortality in critically ill adults with candidemia: a multicenter target trial emulation in France.

Abstract

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. 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. 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 <i>Candida albicans</i> 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. 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. No funding was received for this work.