Intensive Care Medicine

, Volume 43, Issue 11, pp 1668–1677 | Cite as

Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial

  • Anahita Rouzé
  • Séverine Loridant
  • Julien Poissy
  • Benoit Dervaux
  • Boualem Sendid
  • Marjorie Cornu
  • Saad NseirEmail author
  • for the S-TAFE study group
Seven-Day Profile Publication



The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment.


Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β-d-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14 days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7.


A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.001, OR (95% CI) 62.6 (8.1–486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4–13) vs 13 (12–14) days, p < 0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups.


The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy. This trial was registered at, NCT02154178.


Antifungal Empirical (1,3)-β-d-Glucan Mannan Candida Critical illness 


Author contribution

Study concept and design: AR, JP, BS, and SN. Acquisition, analysis, and interpretation of data: all authors. Drafting the manuscript: AR and SN. Statistical and cost-effectiveness analyses: BD and SN. Critical revision of the manuscript: all authors. Study supervision: SN

Compliance with ethical standards

Conflicts of interest

SN: Bayer, MSD, Ciel Medical, and Medtrocic (advisory board, and lecture); other authors: none.

Funding source

University Hospital of Lille received a grant from MSD to support this study in part. MSD had no role in the design, conduct of the study, nor in the analysis or interpretation of study results.

Supplementary material

134_2017_4932_MOESM1_ESM.pdf (237 kb)
Supplementary material 1 (PDF 237 kb)


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Copyright information

© Springer-Verlag GmbH Germany and ESICM 2017

Authors and Affiliations

  1. 1.U995-LIRIC-Lille Inflammation Research International CenterUniv. LilleLilleFrance
  2. 2.U995InsermLilleFrance
  3. 3.Critical Care CenterCHU LilleLilleFrance
  4. 4.Laboratory of Mycology and ParasitologyCHU LilleLilleFrance
  5. 5.UMR 8179CNRSLilleFrance
  6. 6.Public Health and Epidemiology DepartmentCHU LilleLilleFrance

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