Empirical antifungal therapy (EAT) is frequently prescribed to septic critically ill patients with risk factors for invasive Candida infections (ICI). However, among patients without subsequent proven ICI, antifungal discontinuation is rarely performed, resulting in unnecessary antifungal overuse. The investigators postulate that the use of fungal biomarkers could increase the percentage of early discontinuation of EAT among critically ill patients suspected of ICI, as compared with a standard strategy, without negative impact on day 28-mortality. To test this hypothesis, the investigators designed a randomized controlled open-label parallel-group study.
Patients requiring EAT will be randomly assigned to: * intervention group: a strategy in which EAT duration is determined by (1,3)-B-Dglucan and mannan serum assays, performed on day 0 (day of EAT initiation) and day 3. Early stop recommendation, provided before day 7, will be determined using an algorithm based on the results of biomarkers. * control group: a routine care strategy, based on international guidelines, which recommend 14 days of treatment for patients without subsequent proven ICI, and who improve under antifungal treatment, or less in other situations.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
192
EAT duration is determined by β-D-1,3-glucan and mannan serum assays, performed at day 0 (day of EAT initiation) and day 3.
EAT duration is based on IDSA guidelines, which recommend 14 days of treatment for patients without subsequent proven ICI, and who improve under antifungal treatment, or less in other situations.
CH ARRAS
Arras, France
CH de DOUAI
Douai, France
CH Dunkerque
Dunkirk, France
Centre Hospitalier Dr Schaffner
Lens, France
Ch Dr.Schaffner de Lens
Lens, France
Hôpital Roger Salengro, CHU
Lille, France
CH Roubaix
Roubaix, France
CHU de Rouen
Rouen, France
Ch Tourcoing
Tourcoing, France
Centre hospitalier de valenciennes
Valenciennes, France
percentage of patients receiving early discontinuation of EAT, defined as a discontinuation strictly before day 7 after EAT initiation
This trial is designed to demonstrate whether, in critically ill patients suspected for ICI, the biomarker strategy, as compared with a standard strategy, is at the same time: 1. superior in terms of antifungal use and 2. Non-inferior in terms of death
Time frame: day 7 after EAT initiation
death from any cause
This trial is designed to demonstrate whether, in critically ill patients suspected for ICI, the biomarker strategy, as compared with a standard strategy, is at the same time: 1. superior in terms of antifungal use and 2. Non-inferior in terms of death
Time frame: day 28 after EAT initiation
percentage of patients who presented a proven ICI after EAT discontinuation
Time frame: at day 28 or ICU discharge, if it occurs before day 28
percentage of patients who received at least two periods of antifungal treatment (prescribed for separate episodes of suspected or proven ICI)
Time frame: at day 28 or ICU discharge, if it occurs before day 28
intensity of Candida colonization during ICU stay
Five body sites (among urine, anal swabs, pharyngeal swabs, nasal swabs, axillary swabs, gastric aspirates if patients have a nasogastric tube, and tracheal aspirates if patients are intubated or have a tracheotomy) are sampled on day 0 and then once per week for the semi-quantitative determination of yeast colonisation. The number of colony-forming units is scored as follows: score 1, \<10 colony-forming units; score 2, 10 to 50 colony-forming units; score 3, \>50 colony-forming units; score 4, \>50 colony-forming units confluent. Intensity of colonization is determined for each date of sampling, by dividing the sum score for each colonized site by the number of sites sampled giving a mean Candida load. An overall score of \>4 is possible in the case of isolation of several Candida species.
Time frame: at day 28 or ICU discharge, if it occurs before day 28
percentage of patients colonized with a resistant strain of Candida
Time frame: at day 28 or ICU discharge, if it occurs before day 28
antifungal-free days
Time frame: at day 28 or ICU discharge, if it occurs before day 28
ventilator-free days
Time frame: at day 28 or ICU discharge, if it occurs before day 28
ICU-free days
Time frame: at day 28 or ICU discharge, if it occurs before day 28
ICU mortality
Time frame: at day 28 or ICU discharge, if it occurs before day 28
day 90 mortality
Time frame: at day 90
Characterization of the fungal intestinal microbiota studied by standard mycology
Time frame: at baseline, at Day 7, day 14 day 21 and day 28
Characterization of the fungal intestinal microbiota studied by metagenomics
Time frame: at baseline, at Day 7, day 14 day 21 and day 28
Characterization of the bacterial intestinal microbiota studied by culture bacteriology
Time frame: at baseline, at Day 7, day 14 day 21 and day 28
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