Introduction: Critically-ill surgical patients are susceptible to secondary insults, such as nocosomial infections. Current risk stratification of critically-ill patients is largely based on clinical indicators. Efficacy of biomarkers in risk-profiling of these patients has not gained routine clinical applicability. Therefore, we hypothesized that real-time risk analysis can be enhanced by utilizing dynamic markers of inflammation and immune cell activation. This study evaluated the utility of immune-related biomarkers and inflammatory mediators among patients susceptible to nocosomial infection at early time points after surgical ICU admission.

Methods: Forty-four patients considered at risk for subsequent infection were prospectively evaluated from the time of ICU admission until the documentation of an infection. All patients underwent daily clinical surveillance and laboratory analysis to determine activation of polymorphonuclear (PMN) cells (CD11b, CD64) and monocytes (HLA-DR) by flow cytometry. IL-6, TNF levels were assessed by ELISA. Data (mean ± SEM) shown below represent the levels of cell markers in the first 48 hours of ICU admission in those who remained without an infection (-infection) or developed a nocosomial infection (+infection) during the ICU stay.

Results:

	Markers		- Infection	+ Infection
PMN	CD64 (RFI)
	Day1		56 ± 9	87 ± 14
	Day2		58 ± 8	113 ± 17**
PMN	CD11b (RFI)
	Day1		174 ± 30	264 ± 28*
	Day2		151 ± 24	195 ± 19**
Monocytes	HLA-DR (RFI)
	Day1		289 ± 21	275 ± 31*
	Day2		313 ± 24	246 ± 19*
Plasma	IL-6 (pg/ml)
	Day1		255 ± 49	660 ± 204**
	Day2			146 ± 33	548 ± 143**

N (-Infection)=20; N (+infection)=24
*p<0.05; **p<0.01 vs – Infection by t-test
Data represent mean ± SEM; RFI: Relative fluorescence intensity

APACHE II scores at the time of ICU admission were equivalent for the two groups. TNF levels were not significantly different (data not shown). Markers of immune cell activation (CD64, CD11b, IL-6) were higher in patients who developed infections during the ICU course. HLA-DR, a marker of antigen presentation, was inversely related to the development of infection.

Conclusion: The present data suggest critically-ill surgical patients prone to the development of infection exhibit enhanced PMN activation and inflammatory cytokine response as well as decreased monocyte immune surveillance early in the ICU course. This analysis illustrates the clinical utility of real-time biomarker surveys to promote closer scrutiny and possibly earlier intervention in patients at risk for developing nocosomial infections.