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

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. 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. 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. 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.