Literature DB >> 27515019

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

Andrea Cortegiani1, Vincenzo Russotto2, Santi Maurizio Raineri2, Antonino Giarratano2.   

Abstract

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Year:  2016        PMID: 27515019      PMCID: PMC4983743          DOI: 10.1186/s13054-016-1404-4

Source DB:  PubMed          Journal:  Crit Care        ISSN: 1364-8535            Impact factor:   9.097


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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.

Abbreviations

BDG, beta-d-glucan; IFI, invasive fungal infection
  5 in total

1.  (1,3)-β-d-Glucan-based antifungal treatment in critically ill adults at high risk of candidaemia: an observational study.

Authors:  Brunella Posteraro; Mario Tumbarello; Gennaro De Pascale; Elvira Liberto; Maria S Vallecoccia; Elena De Carolis; Valentina Di Gravio; Enrico M Trecarichi; Maurizio Sanguinetti; Massimo Antonelli
Journal:  J Antimicrob Chemother       Date:  2016-04-28       Impact factor: 5.790

Review 2.  Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients.

Authors:  Andrea Cortegiani; Vincenzo Russotto; Alessandra Maggiore; Massimo Attanasio; Alessandro R Naro; Santi Maurizio Raineri; Antonino Giarratano
Journal:  Cochrane Database Syst Rev       Date:  2016-01-16

3.  Discontinuation of empirical antifungal therapy in ICU patients using 1,3-β-d-glucan.

Authors:  Marcio Nucci; Simone A Nouér; Patricia Esteves; Thais Guimarães; Giovanni Breda; Bianca Grassi de Miranda; Flavio Queiroz-Telles; Arnaldo L Colombo
Journal:  J Antimicrob Chemother       Date:  2016-06-10       Impact factor: 5.790

Review 4.  Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy.

Authors:  Thierry Calandra; Jason A Roberts; Massimo Antonelli; Matteo Bassetti; Jean-Louis Vincent
Journal:  Crit Care       Date:  2016-05-27       Impact factor: 9.097

5.  The paradox of the evidence about invasive fungal infection prevention.

Authors:  Andrea Cortegiani; Vincenzo Russotto; Santi Maurizio Raineri; Antonino Giarratano
Journal:  Crit Care       Date:  2016-04-27       Impact factor: 9.097

  5 in total
  3 in total

1.  Should we Administer Antifungal Drugs Before the Diagnosis of Invasive Fungal Infection in Non-Neutropenic Critically Ill Patients?

Authors:  Andrea Cortegiani; Vincenzo Russotto; Santi Maurizio Raineri; Cesare Gregoretti; Antonino Giarratano
Journal:  Turk J Anaesthesiol Reanim       Date:  2016-12-01

2.  Dying with or Because of Invasive Fungal Infection? The Role of Immunity Exhaustion on Patient Outcome.

Authors:  Andrea Cortegiani; Vincenzo Russotto; Santi Maurizio Raineri; Cesare Gregoretti; Antonino Giarratano
Journal:  Turk J Anaesthesiol Reanim       Date:  2016-12-01

3.  Lessons from uncertainty on antifungal treatment in ICU.

Authors:  Andrea Cortegiani; Vincenzo Russotto; Antonino Giarratano
Journal:  J Thorac Dis       Date:  2017-04       Impact factor: 2.895

  3 in total

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