Multicenter study of invasive pulmonary aspergillosis in intensive care units: facing the new challenge

Invasive pulmonary aspergillosis (IPA) is a life-threatening conditions which typically develops in immunosuppressed patients. However admission to intensive care units (ICU) has emerged as a risk factor for the development of IPA, even in those patients without classical risk factors. As the clinical presentation is commonly atypical in non-neutropenic critically ill patients and the isolation of Aspergillus spp. is not always a sign of infection, the diagnosis of this condition often poses a considerable challenge to clinicians. In this retrospective, observational study, all critically ill patients admitted in the ICUs of three hospitals in the Marche region with an Aspergillus spp. isolate obtained from a lower respiratory tract specimen over a six-year period (2019-2024) were classified as infected or colonized according to the main diagnostic criteria, to evaluate differences between colonized and infected patients and factors associated with mortality. A total of 186 patients were identified: in 73 of them IPA was diagnosed with at least one diagnostic algorithm, while 113 were deemed as colonized. Four proven cases were diagnosed by histopathology. Compared to colonized patients, those with IPA more frequently presented with structural lung abnormalities, chronic cardiovascular comorbidity, history of receipt of corticosteroid or other immunosuppressive therapies, severe respiratory viral infection, ARDS, pneumonia, respiratory failure, acute kidney injury, their previous hospitalization was longer, history of receipt antibiotic or antifungal therapy and growth of A. fumigatus; furthermore, galactomannan testing and chest CT were more frequently performed and an antifungal therapy was more frequently prescribed. On the contrary, colonized patients presented higher SOFA score and were more frequently admitted because of hemorrage, stroke or trauma. Thirty-day mortality were higher in the infected group compared to colonized patients (p = 0.11). Factors shown to be independently associated with 30-day mortality were septic shock (OR 4.446, CI 1.022 – 19.339, p 0.047) and infection caused by A. fumigatus (OR 4.486, CI 1.239 – 16.245, p 0.022). Our study confirmed the high mortality of IPA in critically ill patients. Early diagnosis is essential to promptly start an appropriate antifungal treatment, underscoring the potential role of non-culture-based methods and CT-scan in achieving an earlier diagnosis.