Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis

Abstract

Among surgical intensive care unit (SICU) patients, it is difficult to distinguish bacterial sepsis from other causes of systemic inflammatory response syndrome (SIRS). Biomarkers have proven useful to identify the presence of bacterial infection. We enrolled a prospective cohort of 69 SICU patients with suspected sepsis and assayed the concentrations of 9 biomarkers (α-2 macroglobulin [A2M], C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) at baseline, 24, 48, and 72hours. Forty-two patients (61%) had bacterial sepsis by chart review. A2M concentrations were significantly lower, and PCT concentrations were significantly higher in subjects with bacterial sepsis at 3 of 4 time points. Using optimal cutoff values, the combination of baseline A2M and 72-hour PCT achieved a negative predictive value of 75% (95% confidence interval, 54-96%). The combination of A2M and PCT discriminated bacterial sepsis from other SIRS among SICU patients with suspected sepsis.

Keywords: Alpha-2-macroglobulin; Biomarker; Procalcitonin; Sepsis; Surgical intensive care unit; Systemic inflammatory response syndrome.

Figure 1

Longitudinal Biomarker Levels Among Bacterial Sepsis and Other Causes of SIRS. LOESS regression relating biomarker value to actual collection time was performed for each biomarker in each group, with fitting performed by least squares. The line indicates the local mean, colored according to group (bacterial sepsis versus other causes of SIRS); the gray shading indicates the standard error about the mean. A2M, FER, and PCT demonstrate regions of separation between group means. We note that A2M differences are most pronounced at baseline and “24-hours” but diminish at later timepoints. The diminishing difference at later timepoints may reflect A2M synthesis to compensate for a rapid A2M decline in the early phase of sepsis. The FIB local means are highly variable due to outliers.

Figure 2

Individual Biomarker Discrimination Between Bacterial Sepsis and Other Causes of SIRS. Receiver-operating characteristic (ROC) curves are shown for each biomarker at each timepoint. The discrimination of each biomarker, quantified by the C-statistic (equivalent to the area under the ROC curve, AUC) is shown at bottom right of each panel.