Clinical characteristics, radiologic findings, risk factors and outcomes of serum galactomannan-negative invasive pulmonary aspergillosis

Background: The sensitivity of galactomannan (GM) assay is suboptimal for detecting invasive pulmonary aspergillosis (IPA) in serum samples. However, the clinical characteristics, radiologic findings, and outcomes in patients with GM-negative IPA have not been fully elucidated. Methods: Over a 7-year period, adult patients with proven or probable IPA by the EORTC/MSG definition were retrospectively enrolled. Patients with negative GM results and positive Aspergillus spp. cultures from sputum or bronchoalveolar lavage were classified into GM-negative IPA group. GM-positive and culture-negative IPA cases were selected at a 1:2 ratio. Results: Thirty-four patients with GM-negative IPA were compared to 68 randomly selected patients from 158 patients with GM-positive and culture-negative IPA. Patients with diabetes mellitus, chronic kidney disease, and steroid use were more common but those with hematologic malignancy, prior receipt of mold-active antifungal drugs, and neutropenia were less common in GM-negative IPA than in GM-positive IPA. Regarding radiologic findings, angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA. The median number of days from diagnosis to appropriate antifungal therapy was higher in GM-negative IPA than in GM-positive IPA. Multivariate analysis indicated that neutropenia (adjusted odds ratio [aOR], 0.10) and prior receipt of mold-active antifungal drugs (aOR, 0.12) were inversely associated with GM-negative IPA. The 30-day and 90-day mortality were similar between the two groups. Conclusion: Neutropenia and prior receipt of mold-active antifungal drugs before GM assay were independently associated with GM positivity among patients with proven/probable IPA. Angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA. Keywords: Galactomannan, Invasive pulmonary aspergillosis, Neutropeni