Predicting secondary infections using cell-surface markers of immune cell dysfunction: the INFECT study
Critically ill patients are at high risk of secondary infection
This has been associated with failure of key immune cell functions
We have previously identified 3 markers of immune cell function which could additively predict secondary infection1
These measures are :
Neutrophil CD88 - a measure of C5a-mediated neutrophil dysfunction2
Monocyte HLA-DR – a marker of diminished monocyte responsiveness
Percentage of Tregs–an immuno-suppressive subset of T-cells
148 patients recruited from
4 geographically and clinically diverse ICUs
Data available from 138 patients
Infection developed in 51 (37%) of patients. VAP accounted for 55% of infections
Flow cytometers were standardised successfully
High (ICC >0.9) inter and intra-rater reliability of all measures used
Patients developing infection have persistently low CD88
Patients developing infection have persistently low HLA-DR
Patients developing infection have higher proportions of Tregs prior to infection
At optimal cut-off, each marker significantly predicted the subsequent risk of secondary infection with a modest predictive ability
However in combination, predictive ability is significantly enhanced
Modelled clinical use
Identifies a patient as ‘high risk’ of secondary infection
On Day 1 ‘high risk’ patients odds of developing infection were 1.22 (95% CI 0.61-2.46)
By day 2-4 ‘high risk’ patients odds of developing infection were 3.22 (1.42-7.32)
Test remains effective at days 6-8 OR4.76 (1.68-13.48)
‘High risk’ patients identified at day 2-4 also experienced longer length of stay (16 days vs 11 p=0.008) and fewer days alive and free of organ support (5 days vs 9 days p=0.02)
Using this testing approach would lead to a significant reduction in study size or numbers needed to treat for a novel immunomodulatory therapy.
1. Conway Morris A, Anderson N, Brittan M, et al. Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients. British journal of anaesthesia. 2013;111(5):778-787.
2. Morris AC, Brittan M, Wilkinson TS, et al. C5a-mediated neutrophil dysfunction is RhoA-dependent and predicts infection in critically ill patients. Blood. 2011;117(19):5178-5188.
3.Conway Morris A, Datta D, Shankar-Hari M, et al. Predictive value of cell-surface markers in infections in critically ill patients: protocol for an observational study (ImmuNe FailurE in Critical Therapy (INFECT) Study). BMJ Open. 2016;6(7):e011326-e011326.