Combination of Monocyte Human Leukocyte Antigen-DR and β-d-Glucan for the Early Diagnosis of Invasive Candida Infection in Critically Ill Patients: A Proof of Concept Study

Boris Jung (1, 2) , Clément Le Bihan (1) , Pierre Portales (1) , Nathalie Bourgeois (1) , Thierry Vincent (1) , Laurence Lachaud (1) , Gerald Chanques (1, 2) , Matthieu Conseil (1) , Philippe Corne (1) , Pablo Massanet (3) , Jean François Timsit (1) , Samir Jaber (1, 2)

1 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
2 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
3 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes

Background : Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker β-d-glucan in risk stratifying patients for secondary invasive Candida infection (ICI). Methods : Prospective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples (n=286) were collected at day 0, 2 and 7 and mHLA-DR and β-d-glucan were assayed. Secondary invasive Candida sp infection occurrence were then followed. Results : Fifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and β-d-glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of ICI was 6.56[1.24-34.61] for mHLA-DR < 5000 Ab/c and 5.25[0.47-58.9] for BDG > 350pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95%CI 70-92]. Conclusion : This proof of concept study suggests that mHLA-DR predicts ICI in high risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers. Trial registration: ClinicalTrials.gov identifier: NCT03136081 Take home message : Combination of monocytic HLA-DR expression and beta-D-glucan in patients hospitalized for septic shock failed to predict invasive candida infection but could be useful to rule out infection.

Domaines: Sciences du Vivant [q-bio]

Boris Jung, Clément Le Bihan, Pierre Portales, Nathalie Bourgeois, Thierry Vincent, et al.. Combination of Monocyte Human Leukocyte Antigen-DR and β-d-Glucan for the Early Diagnosis of Invasive Candida Infection in Critically Ill Patients: A Proof of Concept Study. 2022. ⟨hal-02949861⟩