Comparison of four diagnostic criteria for invasive pulmonary aspergillosis-A diagnostic accuracy study in critically ill patients.

BACKGROUND: In the absence of lung biopsy, there are various algorithms for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients that rely on clinical signs, underlying conditions, radiological features and mycology. The aim of the present study was to compare four diagnostic algorithms in their ability to differentiate between probable IPA (i.e., requiring treatment) and colonisation. METHODS: For this diagnostic accuracy study, we included a mixed ICU population with a positive Aspergillus culture from respiratory secretions and applied four different diagnostic algorithms to them. We compared agreement among the four algorithms. In a subgroup of patients with lung tissue histopathology available, we determined the sensitivity and specificity of the single algorithms. RESULTS: A total number of 684 critically ill patients (69% medical/31% surgical) were included between 2005 and 2020. Overall, 79% (n = 543) of patients fulfilled the criteria for probable IPA according to at least one diagnostic algorithm. Only 4% of patients (n = 29) fulfilled the criteria for probable IPA according to all four algorithms. Agreement among the four diagnostic criteria was low (Cohen's kappa 0.07-0.29). From 85 patients with histopathological examination of lung tissue, 40% (n = 34) had confirmed IPA. The new EORTC/MSGERC ICU working group criteria had high specificity (0.59 [0.41-0.75]) and sensitivity (0.73 [0.59-0.85]). CONCLUSIONS: In a cohort of mixed ICU patients, the agreement among four algorithms for the diagnosis of IPA was low. Although improved by the latest diagnostic criteria, the discrimination of invasive fungal infection from Aspergillus colonisation in critically ill patients remains challenging and requires further optimization.

Does galactomannan testing increase diagnostic accuracy for IPA in the ICU? A prospective observational study.

BACKGROUND: An algorithm for distinguishing invasive pulmonary aspergillosis (IPA) in critically ill patients (AspICU) has been proposed but not tested. METHODS: This was a prospective observational study applying the AspICU protocol to patients with positive Aspergillus culture (PAC group) and those with negative aspergillus culture but positive galactomannan test in respiratory tract samples (only positive galactomannan (OPG group)). Patients underwent a standardized diagnostic workup with bronchoscopy, computed tomography (CT), and galactomannan determination in serum and bronchoalveolar lavage fluid (BALF). RESULTS: We included 85 patients in the study. Of these, 43 had positive aspergillus cultures and 42 patients had only a positive galactomannan test. There were no statistically significant differences in baseline characteristics, underlying conditions or ICU scores between the two groups. The galactomannan titre in BALF was significantly higher in the positive aspergillus culture (PAC) group (enzyme immunoassay (EIA) 5.9, IQR 3.2-5.7) than in the OPG group (EIA 1.7, IQR 0.9-4.5) (p < 0.001). Classic features of IPA were detected on CT in 37.5 % and 36.6 % of patients in the PAC and OPG groups, respectively. There were no statistically significant differences between the PAC and the OPG group in relation to AspICU or European Organization for the Research and Treatment of Cancer (EORTC) criteria. A positive aspergillus culture was a stronger trigger for initiating antimycotic treatment than positive BALF galactomannan: 88.4 % of patients in the PAC group were regarded by clinicians as having IPA and received antimycotic treatment as opposed to 59.5 % in the OPG group (p = 0.002). The 180-day mortality was 58.1 % in the PAC group and 59.5 % in the OPG group. CONCLUSIONS: The inclusion of BALF galactomannan as an additional entry criterion for the AspICU clinical algorithm could increase the diagnostic sensitivity for IPA in ICU patients. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01866020 ) on 27 May 2013.