Unclassifiable Invasive Pulmonary Aspergillosis in the Intensive Care Unit: Insights From a Multicenter, Retrospective Cohort Study in France (2022–2024)

Background: Suspected invasive pulmonary aspergillosis (IPA) is increasingly treated in intensive care, including in patients without classical immunosuppression. Whether current research definitions (European Organization for Research and Treatment of Cancer [EORTC]/Mycoses Study Group Education and Research Consortium (MSGERC), Invasive Fungal Diseases in Adult Patients in ICU [FUNDICU]) classify treated cases and predict mortality is unclear. Methods: We retrospectively included adults in 48 French intensive care units who received systemic antifungal therapy for suspected IPA (January 2022 to July 2024). Patients were categorized as having modified EORTC/MSGERC probable IPA, FUNDICU probable IPA, or unclassified. Ninety-day mortality was analyzed using multivariable Cox regression; heterogeneity was explored with unsupervised clustering. In adjusted analyses, IPA categorization was not associated with mortality (FUNDICU vs EORTC: adjusted hazard ratio [aHR] = 0.86, 95% CI .62-1.20; unclassified vs EORTC: aHR = 0.89, .62-1.30). Age (aHR 1.03/year, 1.02-1.05), Sequential Organ Failure Assessment (1.06/point, 1.03-1.10), and frailty (1.17/point, 1.07-1.30) independently predicted 90-day mortality. Exploratory clustering identified 6 phenotypes with 90-day mortality ranging from 40% to 80%. Conclusions: Nearly 1 in 5 intensive care patients treated for suspected IPA were not classifiable by EORTC/MSGERC or FUNDICU definitions. Mortality was more strongly associated with age, frailty, and acute severity than with classification category, supporting ICU-focused diagnostic frameworks and risk stratification; these associations should be read in light of the treatment-based design and do not establish that the definitions lack diagnostic value.