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Published on: March 22, 2012
Sequential serum galactomannan as outcome marker for invasive aspergillosis-An exploratory study from the FungiScope
Christina Többen1, Oliver A Cornely1, Carolin S Joisten1
1Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, North Rhine-Westphalia, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, North Rhine-Westphalia, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, North Rhine-Westphalia, Germany.
Background:
Galactomannan index (GMI) is established as a diagnostic tool for invasive aspergillosis (IA), while its utility in monitoring antifungal treatment (AFT) response and prognostic value remains unclear. This study evaluated the validity of serum GM as a biomarker for AFT monitoring and its prognostic significance by correlating GMI with clinical response and survival of IA.
Objectives:
Patients with IA and at least two sequential serum GMI measurements were identified from the FungiScope registry. Joint models of event-time and longitudinal outcome were used for imputing missing GMI to account for the relationship between GMI and time to death, as well as GMI and time to drop-out for the survival analysis and AFT response analysis, respectively. Cox proportional hazards models and logistic regression models assessed survival and clinical response on GMI changes at day 7, with baseline log GMI as an adjustment covariate.
Results:
Among 66 patients with IA, correlation between day 7 GMI predictions and observed values was 92% and 88% in the survival and AFT analysis, respectively. GMI decreased in both patients who died within 42 days and those who survived, but maintained higher in patients who died. GMI increased or declined less in patients who died within 42 days, whereas in survivors, a continuous decline of GMI was observed. Patients with a baseline GMI < 1 had a higher survival rate until day 42 (17/21, 81.0%) compared to those with GMI ≥ 1 (31/45, 68.9%), with a risk of death twice as high as with GMI < 1 (HR = 2.107, P = 0.19).
Conclusion:
Serum GMI is a non-invasive, predictive tool for estimating survival probability at onset of IA. Early GMI changes correlate with survival and could prompt timely AFT adjustment, potentially improving clinical outcomes. Additionally, GMI could serve as surrogate endpoint in clinical trials, facilitating development of new antifungal strategies.
