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Published on: September 19, 2025
Empirical Antifungal Treatment of Critically Ⅲ Patients With Influenza-Associated Acute Respiratory Distress
Stefan Hatzl1,2,3,4, Lisa Kriegl4,5, Christina Geiger5
1Department of Internal Medicine, Intensive Care Unit, Medical University of Graz, Graz, Austria.
Background:
Influenza-associated pulmonary aspergillosis (IAPA) is a significant fungal complication in patients with influenza-induced acute-respiratory-distress-syndrome (ARDS). The impact of empirical antifungal treatment on IAPA incidence and outcomes remains unclear.
Methods:
In this observational multicenter study (9 treatment centers), we included all consecutive patients admitted to intensive care units (ICUs) with influenza-associated ARDS between 1 September 2016 and 1 March 2025. We compared patients receiving empirical antifungal treatment with those who did not, focusing on 30-day IAPA incidence (primary outcome) and survival (secondary outcome). Propensity score weighting was used to account for baseline characteristic imbalances. IAPA cases were classified based on the Fungal-Infections-in-Adult-Patients-in-ICU (FUNDICU) consensus criteria.
Results:
We included 172 patients, 61 (35%) of whom received empirical antifungal therapy (94% posaconazole). IAPA was diagnosed in 24 cases, with a median onset of 2 days after ICU admission. Of these, 20 occurred in the non-treatment group and 4 in the empirical treatment group. The 30-day IAPA incidence was 7.7% in the treatment group and 20.4% in the non-treatment group (P = .002). The sub-distributional hazard ratio (sHR) for IAPA incidence in the empirical treatment group compared with the non-treatment group was 0.21 (95% CI: 0.10-0.92, P = .045). However, there was no significant difference in 30-day ICU survival.
Conclusions:
In ICU patients with influenza ARDS, empirical antifungal treatment was associated with significantly reduced IAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of patients' specific empirical antifungal treatment with regard to IAPA incidence and outcomes.
Insights
Empirical antifungal treatment significantly reduced influenza-associated pulmonary aspergillosis (IAPA) in ICU patients with influenza ARDS. However, this did not improve 30-day survival rates.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Pulmonology
Background:
- Influenza-associated pulmonary aspergillosis (IAPA) is a serious complication in patients with influenza-induced acute respiratory distress syndrome (ARDS).
- The effectiveness of early antifungal treatment for IAPA in this patient group is not well understood.
Purpose of the Study:
- To investigate the impact of empirical antifungal treatment on the incidence of IAPA and patient survival.
- To analyze outcomes in intensive care unit (ICU) patients with influenza-associated ARDS.
Main Methods:
- An observational, multicenter study involving 172 patients with influenza-associated ARDS across 9 ICUs.
- Comparison of outcomes between patients receiving empirical antifungal therapy and those who did not, using propensity score weighting.
- Assessment of 30-day IAPA incidence and survival, with IAPA classification based on FUNDICU criteria.
Main Results:
- IAPA was diagnosed in 24 patients, with a median onset of 2 days post-ICU admission.
- The 30-day IAPA incidence was significantly lower in the empirical antifungal treatment group (7.7%) compared to the non-treatment group (20.4%).
- Empirical antifungal treatment showed a reduced hazard ratio for IAPA incidence (0.21), but no significant difference in 30-day ICU survival was observed.
Conclusions:
- Empirical antifungal treatment is associated with a significant reduction in IAPA incidence among ICU patients with influenza ARDS.
- Despite reduced IAPA incidence, empirical antifungal treatment did not improve 30-day survival.
- Further randomized controlled trials are necessary to confirm the efficacy and safety of empirical antifungal treatment for IAPA and its impact on patient outcomes.
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