Skip to main content

Is it time to combine untargeted antifungal strategies to reach the goal of ‘early’ effective treatment?

A recently published retrospective study by Posteraro et al. [1] investigated the use of (1–3)-β-d-glucan (BDG) as a strategy for antifungal drug administration in patients at high risk of candidemia. The strategy consisted of the administration of antifungals (anidulafungin in most cases) to septic patients with a Candida score ≥ 3 and a positive BDG result (≥80 pg/ml). This untargeted strategy led to better selection of patients, avoiding exposure to antifungals in approximately 73 % of patients with negative BDG results and leading to shortened treatment duration in another 20 % of patients.

Untargeted antifungal treatments (including prophylaxis, pre-emptive and empiric approaches) are the mainstay of early invasive fungal infection (IFI) management [2]. We recently published a Cochrane systematic review investigating the effects of untargeted antifungal treatment in terms of mortality and incidence of IFI in non-neutropenic critically ill patients [3]. Notably, prophylaxis resulted in IFI reduction but it may lead to exposure to antifungals for an unacceptably high proportion of patients, with associated potential adverse effects of antifungals, increased risk of resistance and costs. On the contrary, empiric treatment showed no benefit in terms of IFI reduction and mortality. We hypothesized that this observation may be due to inclusion of patients with a more advanced disease stage [4]. Moreover, many patients receiving antifungals may not need them, leading to the observed lack of benefit. The pre-emptive strategy was less investigated, with only one published randomized controlled study included in the systematic review.

According to the findings of Posteraro et al. [1], a surrogate marker-driven strategy, in association with risk factors, might represent an adequate and cost-effective approach to tailor antifungal treatment to patients who may benefit most. Is it time to abandon classic antifungal treatments to shift towards more pliant ‘early’ antifungal strategies based on risk factors and biomarkers? Data from non-randomized studies suggested that this kind of antifungal strategy might combine advantages of classic treatments with improved selection of patients and reduced exposure to antifungals, also being able to help clinicians to decide when to stop treatments [5]. There is a need for further randomized trials to answer the question of whether surrogate marker/risk factor-based antifungal strategies could be beneficial to our critically ill patients, in comparison with other (old?) untargeted treatments, in terms of efficacy, exposure to antifungals and costs.


BDG, beta-d-glucan; IFI, invasive fungal infection


  1. Posteraro B, Tumbarello M, De Pascale G, Liberto E, Vallecoccia MS, De Carolis E, Di Gravio V, Trecarichi EM, Sanguinetti M, Antonelli M. (1,3)-β-d-Glucan-based antifungal treatment in critically ill adults at high risk of candidaemia: an observational study. J Antimicrob Chemother. 2016;71:2262–69 

  2. Calandra T, Roberts JA, Antonelli M, Bassetti M, Vincent J-L. Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy. Crit Care. 2016;20(1):125.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cortegiani A, Russotto V, Maggiore A, Attanasio M, Naro AR, Raineri SM, Giarratano A. Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev. 2016;1:CD004920.

    PubMed  Google Scholar 

  4. Cortegiani A, Russotto V, Raineri SM, Giarratano A. The paradox of the evidence about invasive fungal infection prevention. Crit Care. 2016;20(1):114.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nucci M, Nouér SA, Esteves P, Guimarães T, Breda G, Miranda BG de, Queiroz-Telles F, Colombo AL. Discontinuation of empirical antifungal therapy in ICU patients using 1,3-β-d-glucan. J. Antimicrob Chemother. 2016;dkw188. doi:10.1093/jac/dkw188.

Download references





Availability of data and materials

All data supporting our thoughts are available through PubMed.

Authors’ contributions

AC and VR conceived the content and drafted the manuscript. SMR and AG helped to conceive the content of this letter and to revise the manuscript critically for important intellectual content. All authors read and approved the final version of the manuscript.

Competing interests

AC, VR and SMR declare that they have no competing interests. AG received grants, fees for educational presentation and advisory board membership, without any relationship to the submitted work, from Pfizer (New York, NY, USA), Merck Sharp (Kenilworth, NJ, USA) and Gilead (Foster City, CA, USA). His institution received a grant from Gilead, Pfizer and Merck Sharp without any relationship to the submitted work.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Not applicable.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Andrea Cortegiani.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cortegiani, A., Russotto, V., Raineri, S.M. et al. Is it time to combine untargeted antifungal strategies to reach the goal of ‘early’ effective treatment?. Crit Care 20, 241 (2016).

Download citation

  • Published:

  • DOI:


  • Septic Patient
  • Potential Adverse Effect
  • Invasive Fungal Infection
  • Antifungal Drug
  • Empiric Treatment