The clinical characteristics, radiologic findings, risk factors and outcome of serum GM-negative IPA

Background: Since the sensitivity of serum galactomannan (GM) is suboptimal, clinicians have difficulty to differentiate serum GM-negative IPA from other invasive mold pneumonia with negative serum GM. However, there are limited data on clinical characteristics of serum GM-negative IPA. We aimed to investigate the clinical risk factors, radiologic findings, and outcome of patients with serum GM-negative IPA compared with those in patients with serum GM-positive IPA.

Methods: Over a 7-year period, adult patients who met the criteria for proven or probable IPA by the revised EORTC/MSG definition were retrospectively enrolled. Among the patients who met the criteria form proven and probable IPA, those with negative serum GM results and positive Aspergillus spp. culture from sputum or bronchoalveolar lavage were classified as serum GM-negative IPA group. Serum GM-positive and culture-negative IPA cases were selected at a 1:2 (serum GM negative/positive) ratio.

Results: There were 34 patients with serum GM-negative IPA. Of the 158 patients with serum GM-positive and culture-negative IPA, 68 patients were randomly selected. Patients with diabetes mellitus, chronic kidney disease, and steroid use were more common but those with hematologic malignancy, and neutropenia were less common in serum GM-negative IPA than those with serum GM-positive IPA, respectively. Interestingly, prior anti-mold therapy before GM assay, which was correlated with neutropenia was less common in serum GM-negative IPA than in serum GM-positive IPA. Median days from diagnosis to appropriate antifungal therapy were longer in serum GM-negative IPA than in serum GM-positive IPA. Regarding radiologic findings, angio-invasive type was less common in serum GM-negative IPA than in serum GM-positive IPA. Multivariate analysis indicated that neutropenia (adjusted odds ratio [aOR], 0.10 [95% CI, 0.04 to 0.31] and prior anti-mold therapy (aOR, 0.12 [95% CI, 0.04 to 0.37] were inversely associated with serum GM-negative IPA. The 30-day and 90-day mortality were similar between the two groups.

Conclusion: Neutropenia and prior anti-mold therapy conversely associated with serum GM-negative IPA. Mortality in patients with serum GM-negative IPA was similar with that in those with serum GM-positive IPA.