Monocyte human leukocyte antigen-DR but not \u03b2-d-glucan may help early diagnosing invasive Candida infection in critically ill patients

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

doi:10.1186/s13613-021-00918-1

Abstract

BackgroundPrecision 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 (IC).MethodsProspective 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 then retrospectively assayed after discharge. Secondary invasive Candida sp infection occurrence was then followed at clinicians’ discretion.ResultsFifty 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 IC was 6.56 [1.24–34.61] for mHLA-DR < 5000 Ab/c and 5.25 [0.47–58.9] for BDG > 350 pg/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].ConclusionsThis study suggests that mHLA-DR may help predicting IC 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.

Highlights

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 assess whether the combination of a host immunoparalysis biomarker and a pathogen-associated biomarker (β-dglucan) would help stratifying critically ill patients with septic shock at risk to develop secondary IC
A cancer was present in 14/50 patients (28%) and was more frequent in IC compared to No invasive Candida infection (NIC) patients (70% vs. 17.5%, p = 0.001)

Summary

Introduction

Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. Current pathogen-associated tools to help diagnose IC either lack of sensitivity (e.g. cultures from sterile sites) or of specificity (clinical prediction scores, molecular biology, β-d-glucan wall biomarker detection) especially in the critically ill population [6, 9, 10]. Because delaying antifungal therapy initiation is a major determinant of clinical outcome [12, 13], intensivists desperately need better tools and/or bundles in the era of precision medicine to better screen patients at risk so their outcome can be improved antifungals over prescription being avoided [14]

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