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

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Abstract

Purpose

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

Methods

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.

Results

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.

Conclusions

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 ClinicalTrials.gov, NCT02154178.

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Author information

Author notes

  1. Séverine Loridant and Julien Poissy contributed equally.

Authors and Affiliations

  1. U995-LIRIC-Lille Inflammation Research International Center, Univ. Lille, 59000, Lille, France

    Anahita Rouzé, Séverine Loridant, Julien Poissy, Boualem Sendid, Marjorie Cornu & Saad Nseir

  2. U995, Inserm, 59000, Lille, France

    Anahita Rouzé, Séverine Loridant, Julien Poissy, Boualem Sendid, Marjorie Cornu & Saad Nseir

  3. Critical Care Center, CHU Lille, 59000, Lille, France

    Anahita Rouzé, Julien Poissy & Saad Nseir

  4. Laboratory of Mycology and Parasitology, CHU Lille, 59000, Lille, France

    Séverine Loridant, Boualem Sendid & Marjorie Cornu

  5. UMR 8179, CNRS, 59000, Lille, France

    Benoit Dervaux

  6. Public Health and Epidemiology Department, CHU Lille, 59000, Lille, France

    Benoit Dervaux

Authors
  1. Anahita Rouzé
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  2. Séverine Loridant
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  3. Julien Poissy
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  4. Benoit Dervaux
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  5. Boualem Sendid
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  6. Marjorie Cornu
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  7. Saad Nseir
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Consortia

for the S-TAFE study group

  • Nadine Francois
  • , Julien Labreuche
  • , Alain Duhamel
  • , Raphaël Favory
  • , Sébastien Préau
  • , Mercé Jourdain
  • , Benoit Voisin
  • , Erika Parmentier-Decrucq
  • , Amélie Cerf
  •  & Daniel Mathieu

Contributions

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

Corresponding author

Correspondence to Saad Nseir.

Ethics declarations

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.

Additional information

Take-home message: The use of a biomarker-based strategy is helpful for early discontinuation of empirical antifungal treatment in critically ill patients with suspected invasive Candida infection, with no negative impact on outcome.

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Cite this article

Rouzé, A., Loridant, S., Poissy, J. et al. Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial. Intensive Care Med 43, 1668–1677 (2017). https://doi.org/10.1007/s00134-017-4932-8

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  • DOI: https://doi.org/10.1007/s00134-017-4932-8

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