Diagnosis Of Probable Invasive Aspergillosis Research Articles

Comparison of different lateral flow assays on bronchoalveolar lavage fluid for invasive aspergillosis screening in non-hematological patients

Several lateral flow assays (LFA) capable of detecting Aspergillus fumigatus in serum and broncho-alveolar lavage fluid (BALF) within the hour, thereby potentially accelerating the screening process, are now commercially available. We prospectively compared three LFA targeting A. fumigatus on BALF collected from non-surgical intensive care patients between June 2022 and February 2023. The three LFA tested were Sõna Aspergillus galactomannan LFA (Immy), Fungadia Aspergillus antigen (Gadia), and AspLFD (OLM Diagnostics). We compared the results of these LFA with those of the galactomannan (GM) PlateliaAspergillus enzyme immunoassay (Bio-Rad), culture on Sabouraud medium and Aspergillus qPCR. We tested 97 BALF samples from 92 patients. In total 84 BALF samples tested negative with all three LFA, and four BALF samples tested positive with the AspLFD assay only (OLM). Only one BALF sample tested positive with the three LFA. In addition, three BALF samples tested positive only with the GM Platelia immunoassay. Four diagnosis of probable invasive aspergillosis were retained for the 92 patients tested. This prospective series included very few positive samples. From a practical point of view, the LFA from OLM presented the simplest protocol for use.

Defining Galactomannan Positivity in the Updated EORTC/MSGERC Consensus Definitions of Invasive Fungal Diseases.

The consensus definitions of invasive fungal diseases from the EORTC/MSGERC were recently revised and updated. They now include consensus cutoff values for the galactomannan test that support the diagnosis of probable invasive aspergillosis. In this supplement article, we provide a rationale for these proposed thresholds based on the test's characteristics and performance in different patient populations and in different specimen types.

2032. Predictors of 6-Week Mortality in Patients with Positive Bronchoalveolar Lavage (BAL) Galactomannan (GM)

BackgroundBAL-GM is a mycologic criterion for diagnosis of probable invasive aspergillosis (IA). However, in a contemporary cohort of consecutive patients with BAL-GM measured as part of their workup for potential IA, we previously showed that 42% of positive (≥0.5) BAL-GM values can be falsely positive; positive predictive value was increased by using higher cutoffs and in patient groups with high pre-test probability for IA. In this study from the same cohort, we analyze the prognostic value of BAL-GM and identify predictors of 6-week mortality, the main outcome in most studies of mold-active antifungal drugs.MethodsWe reviewed clinical and microbiologic data of patients who had ≥1 positive BAL-GM (≥0.5), at Brigham and Women’s Hospital (November 2009–March 2016). We applied EORTC/MSG invasive mold infection (IMI) definitions to classify cases as possible, probable or proven IMI, excluding BAL-GM result as mycologic criterion, and used Cox regression to identify factors associated with 6-week all-cause mortality.ResultsWe studied 134 patients (median age 58 years, 49% women, 55% with hematologic malignancy, 10% solid-organ and 34% hematopoetic stem-cell transplant recipients). APACHE II score, liver disease, acute kidney injury, and shock were independently associated with higher 6-week mortality. ICU stay, mechanical ventilation, corticosteroids, hypertension, EORTC/MSG category, serum-GM and antifungal treatment were associated with higher mortality in univariate, but not multivariate analyses. BAL-GM value was independently associated with 6-week mortality (adjusted HR 1.24(continuous variable), 95% CI 1.1–1.39, P < 0.001). The association of BAL GM strata with 6-week crude mortality was significant in patients with possible, probable or proven IMI, but not in those without IMI (Figure 1). ConclusionHigher BAL-GM values were an independent predictor of 6-week mortality, having prognostic value in patients with possible, probable or proven IMI, but not in patients who did not meet other criteria for IMI. We propose critical reassessment of BAL-GM cutoff values in different patient populations.Figure 1.Kaplan–Meier (KM) curves for different cutoffs of BAL GM.Disclosures All authors: No reported disclosures.

Serum galactomannan assay for diagnosis of probable invasive Aspergillosis in acute leukemia and hematopoietic stem cell transplantation

Background:Invasive aspergillosis (IA) is a leading cause of mortality in acute leukemia and hematopoietic stem cell transplantation (HSCT).Aims:To determine the yield of galactomannan (GM) assay for the diagnosis of probable IA, its temporal relationship with the computed tomography (CT) scans and correlation with mortality in AL and HSCT.Patients and Methods:Consecutive neutropenic episodes (n=150) among inpatients aged ≥15 years with AL or recipients of HSCT were prospectively evaluated over 1½ years. All patients underwent weekly serum GM assay and optical density index >0.5 for ≥2 samples was defined as positive. IA was diagnosed according to EORTC 2008 guidelines.Results:Of the 150 episodes enrolled, 43 (28.7%) were diagnosed with IA: possible 25 (16.7%), probable 17 (11.3%) and proven 1 (0.7%). The yield of GM assay in diagnosing probable IA was 17/42 (40.5%). In 88.2% of probable IA episodes, GM was positive before high-resolution CT at a median of 10 days (range 1-16). In the episodes with ≥2 samples tested, fatality was higher in those ≥2 values positive for GM, compared to the rest (31% vs. 13.2%, odd ratio 2.96, 95% CI 1.09-8.00; P=0.04).Conclusions:In AL and HSCT, GM assay could identify patients with probable IA earlier than CT chest and also predicted a higher risk of death.

Chest Computed Tomography versus Serum Galactomannan Enzyme Immunoassay for the Diagnosis of Probable Invasive Aspergillosis: To Be Decided

Chest Computed Tomography versus Serum Galactomannan Enzyme Immunoassay for the Diagnosis of Probable Invasive Aspergillosis: To Be Decided

Microbiological diagnosis of invasive aspergillosis

Background: Invasive aspergillosis is an important opportunistic fungal infection in highly immunocompromised patients. Clinical diagnosis of invasive aspergillosis remains difficult in that clinical signs and symptoms are nonspecific. Radiologic findings are not pathognomonic but can be suggestive. The isolation of aspergilli from a normally sterile environment, which lacks sensitivity, usually represents a problem. Blood cultures are of limited utility, because the recovery of Aspergillus species from blood cultures invariably represents contamination. Early diagnosis is critical to a medical treatment, but is difficult to achieve with current methods. Measurement of galactomannan and β-D-glucan can be used as an aid in the diagnosis of invasive aspergillosis and it might promote a favourable outcome. The use of polymerase-chain-reaction assay (PCR), although promising, is currently investigational. Conclusions: The verification of aspergillosis requires isolation and microscopic analysis of sterile material showing the fungal structures. Non-culture-based mycological tests, especially assays for the detection of Aspergillus galactomannan and β-D-glucan in serum, or Aspergillus galactomannan in BAL and cerebrospinal fluid specimens are fit to convey useful information and may enable a diagnosis of probable invasive aspergillosis. We may hope that PCR will be improved enough to overcome the limitations of current methods and be developed into a better diagnostic modality for this disease.