Early Identification of Candida in Intra-abdominal Candidiasis

Overview

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.

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.