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. 2012 Jul;43(1):97-106.
doi: 10.1016/j.jemermed.2011.05.072. Epub 2011 Nov 6.

Discriminative value of inflammatory biomarkers for suspected sepsis

Ephraim L Tsalik  1 , L Brett Jaggers, Seth W Glickman, Raymond J Langley, Jennifer C van Velkinburgh, Lawrence P Park, Vance G Fowler, Charles B Cairns, Stephen F Kingsmore, Christopher W Woods
Affiliations

Discriminative value of inflammatory biomarkers for suspected sepsis

Ephraim L Tsalik et al. J Emerg Med. 2012 Jul.

Abstract

Background: Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.

Study objectives: To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.

Methods: PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care.

Results: Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care.

Conclusions: In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.

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Conflict of interest statement

Conflicts of Interest: There are no potential conflicts of interest for ELT, LBJ, SWG, RJL, JCV, LPP, and SFK. VGF has potential conflicts of interest with Cubist, Merck, Theravance, Inhibitex, Cerexa, Leo Pharm, Johnson & Johnson, Arpida, Shire, and Targanta. CBC has a potential conflict of interest with bioMerieux. CWW has potential conflicts of interest with Roche and bioMerieux.

Figures

Figure 1
Figure 1
Median (IQR) PCT, IL-6, and CRP concentrations stratified by likelihood of infection, sepsis severity, and blood culture results. The numerical scale is consistent within each column but differs for each biomarker. Significance testing was performed with Kruskall-Wallis followed by Wilcoxon rank sum tests.
Figure 2
Figure 2
ROC curves for the prediction of infection (left panel) and septicemia (right panel). Infection categories 1–3 define the presence of infection whereas infection category 4 defines the absence of infection.
See this image and copyright information in PMC

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