Post-diagnostic kinetics of the (1 → 3)-β-D-glucan assay in invasive aspergillosis, invasive candidiasis and Pneumocystis jirovecii pneumonia

Abstract

The kinetics of serum (1 → 3)-β-d-glucan (BG) following the diagnosis of invasive fungal disease and administration of antifungal therapy are poorly characterized. It is unknown whether early BG changes have prognostic implications. We assessed the post-diagnostic kinetics of BG in patients with an initial serum BG ≥80 pg/mL and at least one additional post-diagnostic BG value in the setting of invasive aspergillosis (IA, n=69), invasive candidiasis (IC, n=40), or Pneumocystis jirovecii pneumonia (PCP, n = 18), treated with antifungal therapy. Clinical failure of antifungal therapy and mortality were assessed at 6 and 12 weeks, and Cox modelling was used to assess the hazard of initial BG and change in BG at 1 or 2 weeks for these outcomes. In patients with at least two BG values, median initial BG was >500 pg/mL (interquartile range (IQR) 168 to >500; range 80 to >500) in IA, 136 pg/mL (IQR 88 to >500; range 31 to >500) in IC and >500 pg/mL (IQR 235 to >500; range 86 to >500) in PCP. In patients with at least two BG values through to 1 week after diagnosis, overall 1-week decline in BG was 0 pg/mL (IQR 0-53) in IA, 0 (IQR - 65 to 12) in IC and 17 (IQR 0-82) in PCP. Most patients with BG values through 6 and 12 weeks had persistent levels >80 pg/mL. Initial BG and the early trajectory of BG were not predictive of 6-week or 12-week clinical failure or mortality. Whereas BG eventually declines in patients with IA, IC and PCP, it lacks prognostic value within a clinically meaningful time frame.