Invasive Candidiasis
Conditions
Keywords
empirical antifungal therapy, invasive candidiasis, biomarkers, de-escalation, ICU
Brief summary
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.
Detailed description
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.
Interventions
OTHERBiomarker strategy
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.
OTHERRoutine strategy
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.
Sponsors
University Hospital, Lille
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient older than 18 years * Who require EAT for the first time in the ICU (this treatment is prescribed based on the presence of risk factors and clinical suspicion of ICI) * With an expected ICU length of stay of at least 6 days after EAT initiation * Informed written consent
Exclusion criteria
* Neutropenia (neutrophil count \<500 cells /µL) * Active malignant hemopathy * Bone marrow transplantation in the last 6 months * Polyvalent immunoglobulins in the past months * Documented ICI in the past 3 months * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| percentage of patients receiving early discontinuation of EAT, defined as a discontinuation strictly before day 7 after EAT initiation | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| death from any cause | day 28 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 |
| percentage of patients who presented a proven ICI after EAT discontinuation | 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) | at day 28 or ICU discharge, if it occurs before day 28 | — |
| intensity of Candida colonization during ICU stay | at day 28 or ICU discharge, if it occurs before day 28 | 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. |
| percentage of patients colonized with a resistant strain of Candida | at day 28 or ICU discharge, if it occurs before day 28 | — |
| antifungal-free days | at day 28 or ICU discharge, if it occurs before day 28 | — |
| ventilator-free days | at day 28 or ICU discharge, if it occurs before day 28 | — |
| ICU-free days | at day 28 or ICU discharge, if it occurs before day 28 | — |
| ICU mortality | at day 28 or ICU discharge, if it occurs before day 28 | — |
| day 90 mortality | at day 90 | — |
| Characterization of the fungal intestinal microbiota studied by standard mycology | at baseline, at Day 7, day 14 day 21 and day 28 | — |
| Characterization of the fungal intestinal microbiota studied by metagenomics | at baseline, at Day 7, day 14 day 21 and day 28 | — |
| Characterization of the bacterial intestinal microbiota studied by culture bacteriology | at baseline, at Day 7, day 14 day 21 and day 28 | — |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORAnahita Rouze, MD
University Hospital, Lille
Outcome results
None listed