Unclassifiable Invasive Pulmonary Aspergillosis in the ICU: insights from a multicenter, retrospective cohort study in France (2022-2024)
Antoine Villa, Benoit Painvin, Antoine Hérault, Pierre-Marie Bourgeois, Bastien Peiffer, Sibylle Cunat, Fanny Vincent, Luc Juban, Luc Desmedt, Marine De Bony, Marin Caumartin, Rania Bounab, Loïc Prez, Julien Dessajan, François Dhelft, Jérémie Mallet, Marc Pineton de Chambrun, Grégoire Fourcade, Cédric Darreau, Donatien de Marignan, Guillaume Louis, Florent Wallet, Maxime Desgrouas, Kévin Vanneck Kamdem, Hamza Chraibi, Florian Reizine, Tomas Urbina, Françoise Botterel, Fanny Lanternier, Laurence Millon, Saad Nseir, Nicolas de Prost, , Jonathan Chelly, Marc Gainnier, Octave Cannac, Martin Cour, Emmanuelle Guérin, Sébastien Jochmans, Loïc Le Guennec, Damien Contou, Adrien Pons, Jean-Pierre Quenot, Fabrice Uhel, Asaël Berger, Maxens Decavele, Antoine Guillon, Pascal Beuret, Cindy Lage, Djamel Mokart, Octave Cannac, Victor Penaud, Antoine Lafarge, Julien Maizel, Rémy Nyga, Jean-Philippe Rigaud, Matthieu Turpin, Sophie Nagle, Pierre Bay, Keyvan RazaziAbstract
Background
Suspected invasive pulmonary aspergillosis (IPA) is increasingly treated in intensive care, including in patients without classical immunosuppression. Whether current research definitions (EORTC/MSGERC, 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-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.
Results
Among 371 treated patients, 217 (58%) met modified EORTC, 83 (22%) met FUNDICU, and 71 (19%) were unclassified. Overall, 90-day mortality was 62% and survival did not differ by category (63%, 63%, 58%; log-rank p=0.24). In adjusted analyses, IPA categorization was not associated with mortality (FUNDICU vs EORTC: adjusted hazard ratio (aHR)=0.86, 95% CI 0.62-1.20; unclassified vs EORTC: aHR=0.89, 0.62-1.30). Age (aHR 1.03/year, 1.02-1.05), SOFA (1.06/point, 1.03-1.10), and frailty (1.17/point, 1.07-1.30) independently predicted 90-day mortality. Exploratory clustering identified six phenotypes with 90-day mortality ranging from 40% to 80%.
Conclusions
Nearly one in five 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.