Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 2;8(3):ofab080.
doi: 10.1093/ofid/ofab080. eCollection 2021 Mar.

Performance of Repeated Measures of (1-3)-β-D-Glucan, Mannan Antigen, and Antimannan Antibodies for the Diagnosis of Invasive Candidiasis in ICU Patients: A Preplanned Ancillary Analysis of the EMPIRICUS Randomized Clinical Trial

Claire Dupuis  1   2 , Clément Le Bihan  3 , Daniele Maubon  4 , Laure Calvet  1 , Stéphane Ruckly  5 , Carole Schwebel  6 , Lila Bouadma  2   7 , Elie Azoulay  8 , Muriel Cornet  4 , Jean-Francois Timsit  2   7 ; Empiricus Study Group
Collaborators, Affiliations

Performance of Repeated Measures of (1-3)-β-D-Glucan, Mannan Antigen, and Antimannan Antibodies for the Diagnosis of Invasive Candidiasis in ICU Patients: A Preplanned Ancillary Analysis of the EMPIRICUS Randomized Clinical Trial

Claire Dupuis et al. Open Forum Infect Dis. .

Abstract

Background: We aimed to assess the prognostic value of repeated measurements of serum (1-3)-β-D-glucan (BDG), mannan-antigen (mannan-Ag), and antimannan antibodies (antimannan-Ab) for the occurrence of invasive candidiasis (IC) in a high-risk nonimmunocompromised population.

Methods: This was a preplanned ancillary analysis of the EMPIRICUS Randomized Clinical Trial, including nonimmunocompromised critically ill patients with intensive care unit-acquired sepsis, multiple Candida colonization, and multiple organ failure who were exposed to broad-spectrum antibacterial agents. BDG (>80 and >250 pg/mL), mannan-Ag (>125 pg/mL), and antimannan-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 biomarkers were then studied in the subgroup of patients who were still alive at day 3 and free of IC (cohort 2).

Results: Two hundred thirty-four patients were included, and 215 were still alive and free of IC at day 3. IC developed in 27 patients (11.5%), and day 28 mortality was 29.1%. Finally, BDG >80 pg/mL at inclusion was associated with an increased risk of IC (CSHR[IC], 4.67; 95% CI, 1.61-13.5) but not death (CSHR[death], 1.20; 95% CI, 0.71-2.02).

Conclusions: Among high-risk patients, a first measurement of BDG >80 pg/mL was strongly associated with the occurrence of IC. Neither a cutoff 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%, which calls into question the efficacy of empirical therapy in this subgroup.

Keywords: (1,3)-β-D-glucan; competing risk models; invasive candidiasis.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Flowchart. Abbreviations: IC, invasive candidiasis; RCT, randomized controlled trial.
Figure 2.
Figure 2.
Cumulative incidence of IC and death depending on the levels of BDG (+/- 80 pg/mL) on inclusion. Abbreviations: BDG, serum (1–3)-β-D-glucan; IC, invasive candidiasis.
See this image and copyright information in PMC

References

    1. Paiva JA, Pereira JM, Tabah A, et al. . Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study. Crit Care 2016; 20:53. - PMC - PubMed
    1. Kett DH, Azoulay E, Echeverria PM, Vincent JL; Extended Prevalence of Infection in ICU Study (EPIC II) Group of Investigators . Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med 2011; 39:665–70. - PubMed
    1. Vincent JL, Rello J, Marshall J, et al. . EPIC II Group of Investigators . International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302:2323–9. - PubMed
    1. Lortholary O, Renaudat C, Sitbon K, et al. . The French Mycosis Study Group . Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010). Intensive Care Med 2014; 40:1303–12. - PMC - PubMed
    1. Bassetti M, Garnacho-Montero J, Calandra T, et al. . Intensive care medicine research agenda on invasive fungal infection in critically ill patients. Intensive Care Med 2017; 43:1225–38. - PubMed