Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data

Abstract

Purpose: Systemic antifungal therapy (SAT) of invasive candidiasis needs to be initiated immediately upon clinical suspicion. Controversies exist about adequate time and potential harm of antifungal de-escalation (DE) in documented and suspected candidiasis in ICU patients. Our objective was to investigate whether de-escalation within 5 days of antifungal initiation is associated with an increase of the 28-day mortality in SAT-treated non-neutropenic adult ICU patients.

Methods: From the 835 non-neutropenic adults recruited in the multicenter prospective observational AmarCAND2 study, we selected the patients receiving systemic antifungal therapy for a documented or suspected invasive candidiasis in the ICU and who were still alive 5 days after SAT initiation. They were included into two groups according to the occurrence of observed SAT de-escalation before day 6. The average causal SAT de-escalation effect on 28-day mortality was evaluated by using a double robust estimation.

Results: Among the 647 included patients, early de-escalation at day 5 after antifungal initiation occurred in 142 patients (22%), including 48 (34%) patients whose SAT was stopped before day 6. After adjustment for the baseline confounders, early SAT de-escalation was the solely factor not associated with increased 28-day mortality (RR 1.12, 95% CI 0.76-1.66).

Conclusion: In non-neutropenic critically ill adult patients with documented or suspected invasive candidiasis, SAT de-escalation within 5 days was not related to increased day-28 mortality but it was associated with decreased SAT consumption. These results suggest for the first time that SAT de-escalation may be safe in these patients.

Keywords: Antifungal; Causal inference; De-escalation; Intensive care unit; Invasive candidiasis; Outcome; Sepsis.