Early Identification of Candida in Intra-abdominal Candidiasis

Study Overview
=================
Brief Summary
-----------------
Intra-abdominal candidiasis remains the first origin of invasive candidiasis in critically ill patients with a mortality up to 60%. This high mortality is partly related to delay of anti-fungal treatment administration. According to experts in the field, new diagnostic methods to rapidly detect Candida in intra-abdominal infections is mandatory because the current strategies suffer from a lack of both sensitivity and specificity. The calscreener (SYMCEL®) is a new diagnostic tool to rapidly identify the presence of pathogens in biological samples based on micrometabolic activity detection. This technology also allows to measure the metabolic activity of pathogens. The ICCA project will test the feasibility, the accuracy and the diagnostic performance of the calscreener on an existing biological collection of peritoneal fluid. This collection came from a cohort of critically ill patients with intra-abdominal infection which required abdominal surgery. Intra-abdominal infections consist of bacterial peritonitis and intra-abdominal candidiasis. The presence of pathogens (bacteria and yeast) is already known, the peritoneal fluid being stored after routine analysis (bacteriology / mycology). In addition to the detection / identification of yeast will be investigated in this project, the cal screener will be used to evaluate the metabolic profile of Candida albicans in the peritoneal fluid, alone and with bacteria. This objective aims to evaluate the virulence of Candida in the peritoneal fluid from a metabolic perspective. The results will be compared to phenotypic and molecular evaluation.

Detailed Description
-----------------
The high mortality rate of patients with intra-abdominal candidiasis infection is partly related to delay in anti-fungal treatment. The gold standard method for Candida detection remains the yeast culture on mycological media which suffers from a delayed response time (up to 5 days). Consequently, in the routine practice, the decision to start an anti-fungal treatment is based on predictive scores such as the Peritonitis score. Whatever the score, they all suffer from a lack of sensitivity and specificity and could expose ICU patients to delayed treatment with negative impact on mortality. Once introduced and before the availability of the result of the culture, the anti-fungal can be stopped based on two serum measures of 1,3 beta D Glucan < 80 pg/ml. This strategy allows anti-fungal spare. Therefore, there is a room for improvement regarding early Candida detection and identification for the right choice of anti-fungal. The calscreener (SYMCEL®) is a new diagnostic tool to rapidly identify the presence of pathogens in biological samples based on micrometabolic activity detection. The metabolic activity anticipates the future positive culture. To date, most of the experiments with the calscreenerTM concern bacteria. During the development phase, some experiments have been performed with Candida, mostly in vitro. Data of feasibility with clinical samples such as the peritoneal fluid are lacking. Besides, there is currently no library regarding the metabolic profile of Candida, in both albicans and non-albicans species. All in all, its routine use is currently impossible. First results (unpublished data from our team) of metabolic activity detection in peritoneal fluid with known presence of Candida showed a time detection <1 hour. We aim to confirm these promising results using biological samples collected in an ongoing cohort study. We first need to describe the metabolic activity curves of different Candida species in order to constitute a library. The heat production of each peritoneal fluid will be measured, and then compared considering the presence or absence of bacteria. Then, to explain the metabolic activity, a phenotypic evaluation of candida (growth and yeast-to-hyphae transition) and molecular evaluation (level of expression of virulence gene) will be performed.

Official Title
-----------------
The ICCA Study (Early Identification of Candida in Intra-abdominal CAndidiasis)

Conditions
-----------------
Candida Sepsis, Candidiasis, Invasive, Peritonitis Infectious, Critically Ill

Intervention / Treatment
-----------------
* Diagnostic Test: calscreener
* Other: Metabolic profile
* Other: optical microscopy
* Other: RTqPCR


Participation Criteria
=================
Eligibility Criteria
-----------------
The criteria belong to the pBDG2 study (Peritoneal 1.3-ß-D-glucan for the Diagnosis of Intra-abdominal Candidiasis in Critically Ill Patients). Inclusion Criteria: adult Covered by health insurance Admitted in ICU with intra-abdominal infection requiring abdominal surgery or percutaneous drainage Exclusion Criteria: Pregnant or lactating woman Patient deprived of liberty after administration of juridical decision Patient under psychiatric care
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| critically ill adult patients with intra-abdominal infection<br>The ICCA study is an ancillary study of a non-interventional prospective cohort study (the pBDG2 study, NCT03997929) The pBDG 2 study has enrolled ICU patients with intra-abdominal infection requiring abdominal surgery. During the surgery, peritoneal fluid has been collected to identify the pathogens involved and guide anti-infective therapies. After the routine analyses, the remained peritoneal fluid was stored to create a biological collection. This biological collection, in which the content of bacterias and yeasts is known, will be analysed with the calscreener. | Diagnostic Test: calscreener<br>* The calscreener (SYMCEL®) is a new diagnostic tool to rapidly identify the presence of pathogens in biological samples based on micrometabolic activity detection. All living cells produce heat by the chemical and physical processes of life; by monitoring the heat flow over time (J/s, W) a significant amount of information can be obtained regarding the biological system.<br>Other: Metabolic profile<br>* The cal screener allows the measure of metabolic activity of pathogens directly from a sample (here, the peritoneal fluid). The heat production will be compared between peritoneal fluid, with or without addition of bacteria<br>Other: optical microscopy<br>* To explain the metabolic activity, growth and yeast-to-hyphae transition will be analysed using optical microscopy and conventional culture<br>Other: RTqPCR<br>* To explain the metabolic activity, level of expression of 5 Candida albicans virulence genes (UME6, ALS3, SFL2, HWP1 and ECE1) will be address and compared between peritoneal fluid.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection (Yes/No) of the presence of Candida in the peritoneal fluid | Detection by the calscreener : detection of metabolic activity > 5 µW (according to SYMCEL recommendation) | Day 1 - 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay (in hours) of detection | Delay (in hours) from the start of calscreener analysis to first detection of heat flow > 5 µW | Day 1 - 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diagnostic method, metabolic profile, virulence, intra abdominal candidiasis, candida