Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, adult patients: A systematic review with qualitative evidence synthesis

•This systematic review will guide discussions within the FUNDICU project.•Most available data pertained to IPA.•The AspICU definition showed a promising diagnostic performance against histology.•A better diagnostic performance of BALF GM than serum GM was observed.•Suboptimal specificity was observed for BALF and serum (1,3)-β-D-glucan. To summarize the available evidence on the diagnostic performance for invasive aspergillosis (IA) in non-hematological, non-solid organ transplantation critically ill patients of the following: (i) existing definitions of IA (developed either for classical immunocompromised populations or for non-immunocompromised critically ill patients); (ii) laboratory tests; (iii) radiology tests. A systematic review was performed by evaluating studies assessing the diagnostic performance for IA of a definition/s and/or laboratory/radiology test/s vs. a reference standard (histology) or a reference definition. Sufficient data for evaluating the performance of existing definitions and laboratory tests for the diagnosis of IA in critically ill patients is available only for invasive pulmonary aspergillosis. Against histology/autopsy as reference, the AspICU definition showed a promising diagnostic performance but based on small samples and applicable only to patients with positive respiratory cultures. Studies on laboratory tests consistently indicated a better diagnostic performance of bronchoalveolar lavage fluid (BALF) galactomannan (GM) than serum GM, and a suboptimal specificity of BALF and serum (1,3)-β-D-glucan. Evidence stemming from this systematic review will guide the discussion for defining invasive aspergillosis within the FUNDICU project. The project aims to develop a standard set of definitions for invasive fungal diseases in critically ill, adult patients.