Performance of repeated measures of (1-3)-β-D-glucan, mannan antigen and anti-mannan antibodies for the diagnosis of Invasive Candidiasis in ICU patients: a preplanned ancillary analysis of the EMPIRICUS Randomized Clinical Trial

Background We aimed to assess the prognostic value of repeated measurements of serum (1-3)-β-D-glucan(BDG), mannan-antigen(mannan-Ag) and anti-mannan antibodies(anti-mannan-Ab) on the occurrence of Invasive Candidiasis(IC) in a high risk non-immunocompromised population. Methods It is a preplanned ancillary analysis of the EMPIRICUS Randomized Clinical Trial, including non-immunocompromised critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents. BDG(>80 and >250 pg/mL), mannan-Ag(>125 pg/mL) and anti-mannan-Ab(>10 AU) were collected repeatedly. We used cause-specific hazard models. Biomarkers were assessed at baseline in the whole cohort(cohort 1). Baseline covariates and/or repeated measurements and/or increased of biomarkers were then studied in the subgroup of patients who were still alive at day 3 and free of IC(cohort 2). Results 234 patients were included and 215 were still alive and free of IC at day 3. IC developed in 27(11.5%) and day-28 mortality was 29.1%. Finally, only BDG>80 pg/ml at inclusion was associated with an increased risk of IC(CSHR[IC]=4.67, CI95% 1.61-13.5) but not death (CSHR[death]=1.20, CI95% 0.71-2.02). Conclusions Among high risk patients, a first measurement of BDG over 80 pg/mL was strongly associated with the occurrence of IC. Neither a cut off-of 250 pg/mL nor repeated measurements of fungal biomarkers seemed to be useful to predict the occurrence of IC. The cumulative risk of IC in the placebo group if BDG>80 pg/ml was 25.39% questioning about the potential interest of empirical therapy in this subgroup.