The soluble mannose receptor (sMR/sCD206) in critically ill patients with invasive fungal infections, bacterial infections or non-infectious inflammation: a secondary analysis of the EPaNIC RCT.
Aged
Analysis of Variance
Bacterial Infections
/ blood
Biomarkers
/ analysis
Critical Illness
/ epidemiology
Female
Humans
Inflammation
/ blood
Invasive Fungal Infections
/ blood
Lectins, C-Type
/ analysis
Male
Mannose Receptor
Mannose-Binding Lectins
/ analysis
Middle Aged
ROC Curve
Receptors, Cell Surface
/ analysis
Time Factors
Inflammation
Invasive fungal infection
Macrophage activation
Soluble CD206
Soluble mannose receptor
sCD206
sMR
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
02 Aug 2019
02 Aug 2019
Historique:
received:
19
06
2019
accepted:
22
07
2019
entrez:
4
8
2019
pubmed:
4
8
2019
medline:
11
2
2020
Statut:
epublish
Résumé
Invasive fungal infections (IFI) are difficult to diagnose, especially in critically ill patients. As the mannose receptor (MR) is shed from macrophage cell surfaces after exposure to fungi, we investigate whether its soluble serum form (sMR) can serve as a biomarker of IFI. This is a secondary analysis of the multicentre randomised controlled trial (EPaNIC, n = 4640) that investigated the impact of initiating supplemental parenteral nutrition (PN) early during critical illness (Early-PN) as compared to withholding it in the first week of intensive care (Late-PN). Serum sMR concentrations were measured in three matched patient groups (proven/probable IFI, n = 82; bacterial infection, n = 80; non-infectious inflammation, n = 77) on the day of antimicrobial initiation or matched intensive care unit day and the five preceding days, as well as in matched healthy controls (n = 59). Independent determinants of sMR concentration were identified via multivariable linear regression. Serum sMR time profiles were analysed with repeated-measures ANOVA. Predictive properties were assessed via area under the receiver operating curve (aROC). Serum sMR was higher in IFI patients than in all other groups (all p < 0.02), aROC to differentiate IFI from no IFI being 0.65 (p < 0.001). The ability of serum sMR to discriminate infectious from non-infectious inflammation was better with an aROC of 0.68 (p < 0.001). The sMR concentrations were already elevated up to 5 days before antimicrobial initiation and remained stable over time. Multivariable linear regression analysis showed that an infection or an IFI, higher severity of illness and sepsis upon admission were associated with higher sMR levels; urgent admission and Late-PN were independently associated with lower sMR concentrations. Serum sMR concentrations were higher in critically ill patients with IFI than in those with a bacterial infection or with non-infectious inflammation. However, test properties were insufficient for diagnostic purposes.
Sections du résumé
BACKGROUND
BACKGROUND
Invasive fungal infections (IFI) are difficult to diagnose, especially in critically ill patients. As the mannose receptor (MR) is shed from macrophage cell surfaces after exposure to fungi, we investigate whether its soluble serum form (sMR) can serve as a biomarker of IFI.
METHODS
METHODS
This is a secondary analysis of the multicentre randomised controlled trial (EPaNIC, n = 4640) that investigated the impact of initiating supplemental parenteral nutrition (PN) early during critical illness (Early-PN) as compared to withholding it in the first week of intensive care (Late-PN). Serum sMR concentrations were measured in three matched patient groups (proven/probable IFI, n = 82; bacterial infection, n = 80; non-infectious inflammation, n = 77) on the day of antimicrobial initiation or matched intensive care unit day and the five preceding days, as well as in matched healthy controls (n = 59). Independent determinants of sMR concentration were identified via multivariable linear regression. Serum sMR time profiles were analysed with repeated-measures ANOVA. Predictive properties were assessed via area under the receiver operating curve (aROC).
RESULTS
RESULTS
Serum sMR was higher in IFI patients than in all other groups (all p < 0.02), aROC to differentiate IFI from no IFI being 0.65 (p < 0.001). The ability of serum sMR to discriminate infectious from non-infectious inflammation was better with an aROC of 0.68 (p < 0.001). The sMR concentrations were already elevated up to 5 days before antimicrobial initiation and remained stable over time. Multivariable linear regression analysis showed that an infection or an IFI, higher severity of illness and sepsis upon admission were associated with higher sMR levels; urgent admission and Late-PN were independently associated with lower sMR concentrations.
CONCLUSION
CONCLUSIONS
Serum sMR concentrations were higher in critically ill patients with IFI than in those with a bacterial infection or with non-infectious inflammation. However, test properties were insufficient for diagnostic purposes.
Identifiants
pubmed: 31375142
doi: 10.1186/s13054-019-2549-8
pii: 10.1186/s13054-019-2549-8
pmc: PMC6679534
doi:
Substances chimiques
Biomarkers
0
Lectins, C-Type
0
Mannose Receptor
0
Mannose-Binding Lectins
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
270Subventions
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 170719N
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 1832817N
Organisme : Fonds Wetenschappelijk Onderzoek
ID : G.0399.12
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 1805116N
Organisme : Vlaamse regering
ID : METH/14/06
Organisme : Horizon 2020
ID : AdvG-2017-785809
Organisme : European Research Council
ID : ERC AdvG-2012_321670
Pays : International
Organisme : KU Leuven
ID : STG/16/021
Organisme : KU Leuven
ID : C24/17/070
Organisme : Universitaire Ziekenhuizen Leuven, KU Leuven
ID : Clinical Research Foundation
Organisme : Innovationsfonden
ID : 0603-00413B
Références
Microbes Infect. 2000 Sep;2(11):1305-10
pubmed: 11018446
Clin Infect Dis. 2008 Jun 15;46(12):1813-21
pubmed: 18462102
JAMA. 2009 Dec 2;302(21):2323-9
pubmed: 19952319
J Biol Chem. 2011 Mar 11;286(10):7822-9
pubmed: 21205820
N Engl J Med. 2011 Aug 11;365(6):506-17
pubmed: 21714640
Crit Care. 2011 Jul 28;15(4):R183
pubmed: 21798063
Crit Care. 2012 May 25;16(3):R96
pubmed: 22632574
J Leukoc Biol. 2012 Dec;92(6):1177-86
pubmed: 22966131
Clin Microbiol Infect. 2012 Dec;18 Suppl 7:19-37
pubmed: 23137135
Clin Chem Lab Med. 2014 Mar;52(3):453-61
pubmed: 24114918
Eur J Clin Microbiol Infect Dis. 2014 Jan;33(1):117-22
pubmed: 24424890
PLoS One. 2014 Mar 17;9(3):e92331
pubmed: 24637679
Clin Microbiol Rev. 2014 Jul;27(3):490-526
pubmed: 24982319
Infect Dis (Lond). 2015 Apr;47(4):203-8
pubmed: 25650730
Am J Respir Crit Care Med. 2015 May 15;191(10):1139-46
pubmed: 25780856
Leuk Res. 2015 Sep;39(9):971-5
pubmed: 26169445
Nat Rev Microbiol. 2016 Mar;14(3):163-76
pubmed: 26853116
Oncotarget. 2016 Apr 19;7(16):21484-95
pubmed: 26910891
PLoS One. 2016 May 06;11(5):e0154944
pubmed: 27152615
JAMA. 2016 Oct 18;316(15):1555-1564
pubmed: 27706483
Oncol Lett. 2017 Sep;14(3):2982-2990
pubmed: 28928836
Scand J Clin Lab Invest. 2018 May;78(3):180-186
pubmed: 29383956
Clin Microbiol Infect. 2019 Mar;25(3):359-364
pubmed: 29870854
Crit Care Med. 1985 Oct;13(10):818-29
pubmed: 3928249