Korean J Lab Med.  2009 Dec;29(6):529-535. 10.3343/kjlm.2009.29.6.529.

Comparison of Diagnostic Utility between Procalcitonin and C-Reactive Protein for the Patients with Blood Culture-Positive Sepsis

• Hur M
• Moon HW
• Yun YM
• Kim KH
• Kim HS
• Lee KM

• KMID: 1781606
• DOI: http://doi.org/10.3343/kjlm.2009.29.6.529

Abstract

BACKGROUND
Procalcitonin (PCT) is a relatively new marker for bacterial infections, and its diagnostic utility has been variable across the studies. We investigated the diagnostic utility of PCT for the patients with blood culture-positive sepsis, and compared it with that of C-reactive protein (CRP). METHODS: In 1,270 consecutive blood samples, PCT and CRP were simultaneously measured and results were compared according to the five categories of PCT concentrations (<0.05 ng/mL; 0.05-0.49 ng/mL; 0.5-1.99 ng/mL; 2-9.99 ng/mL; > or =10 ng/mL). In 506 samples, they were further analyzed according to the result of blood culture. PCT and CRP were measured using enzyme-linked fluorescent assay (bioMerieux Co., France) and rate nephelometry (Beckman Coulter Co., USA), respectively. Their diagnostic utilities were compared using ROC curves. RESULTS: The mean concentrations of CRP in five categories of PCT were 15.4 mg/L, 42.1 mg/L, 101.2 mg/L, 125.0 mg/L, 167.1 mg/L, respectively (P<0.0001). Both PCT and CRP showed significant differences between the two positive and negative groups of blood culture (PCT, 8.47 vs 2.44 ng/mL, P=0.0133; CRP, 110.48 vs 59.78 mg/L, P<0.0001). The areas under the ROC curves (95% confidence interval) for PCT and CRP were 0.720 (0.644-0.788) and 0.558 (0.478-0.636), respectively, and showed a significant difference (P=0.005). CONCLUSIONS: The diagnostic utility of PCT is superior to that of CRP for the patients with blood culture-positive sepsis. PCT seems to be reliable for sepsis diagnosis, and may provide useful information for the critically ill patients.

Keyword

Procalcitonin; C-reactive protein; Sepsis

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Biological Markers/blood
C-Reactive Protein/*analysis
Calcitonin/*blood
Child
Child, Preschool
Enzyme-Linked Immunosorbent Assay
Humans
Infant
Infant, Newborn
Middle Aged
Nephelometry and Turbidimetry
Protein Precursors/*blood
ROC Curve
Reagent Kits, Diagnostic
Sensitivity and Specificity
Sepsis/*diagnosis

Figure

• 

  Fig. 1. Comparison of C-reactive protein according to the five groups of procalcitonin concentration. P<0.0001 (F value=100.11, ANOVA). The central box represents the values from the lower to upper quartile (25 to 75 percentile) with the middle line for mean. Procalcitonin concentrations were divided into five groups: see Table 1.

• 

  Fig. 2. Comparison of PCT levels between the two groups of blood culture (8.47 ng/mL vs 2.44 ng/mL, P=0.0133, t-test). The central box represents the values from the lower to upper quartile (25 to 75 percentile) with the middle line for mean. Abbreviations: PCT, procalcitonin; n, number.

• 

  Fig. 3. Comparison of C-reactive protein levels between the two groups of blood culture (110.48 mg/L vs 59.78 mg/L, P<0.0001, t-test). The central box represents the values from the lower to upper quartile (25 to 75 percentile) with the middle line for mean. Abbreviations: CRP, C-reactive protein; n, number.

• 

  Fig. 4. Pairwise comparison of ROC curves of PCT and CRP (n= 161). The areas under the ROC curve (95% confidence interval, CI) for PCT and CRP were 0.720 (0.644-0.788) and 0.558 (0.478-0.636), respectively, with a significant difference between the areas of 0.162 (95% CI=0.048-0.227, P=0.005). Abbreviations: See Table 1.

Reference

1.Pfäfflin A., Schleicher E. Inflammation markers in point-of-care testing (POCT). Anal Bioanal Chem. 2009. 393:1473–80.

2.American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992. 20:864–74.

3.Levy MM., Fink MP., Marshall JC., Abraham E., Angus D., Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003. 31:1250–6.

4.Mitaka C. Clinical laboratory differentiation of infectious versus non-infectious systemic inflammatory response syndrome. Clin Chim Acta. 2005. 351:17–29.

5.Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta. 2002. 323:17–29.

6.Becker KL., Snider R., Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008. 36:941–52.

7.Chua AP., Lee KH. Procalcitonin in severe acute respiratory syndrome (SARS). J Infect. 2004. 48:303–6.

8.Cone JB. Inflammation. Am J Surg. 2001. 182:558–62.

9.Luster AD. Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med. 1998. 338:436–45.

10.Simon L., Gauvin F., Amre DK., Saint-Louis P., Lacroix J. Serum pro-calcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004. 39:206–17.

11.Whicher J., Bienvenu J., Monneret G. Procalcitonin as an acute phase marker. Ann Clin Biochem. 2001. 38:483–93.

12.Nijsten MW., Olinga P., The TH., de Vries EG., Koops HS., Groothuis GM, et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med. 2000. 28:458–61.

13.Assicot M., Gendrel D., Carsin H., Raymond J., Guilbaud J., Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993. 341:515–8.

14.Brunkhorst FM., Al-Nawas B., Krummenauer F., Forycki ZF., Shah PM. Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia. Clin Microbiol Infect. 2002. 8:93–100.

15.Oberhoffer M., Vogelsang H., Russwurm S., Hartung T., Reinhart K. Outcome prediction by traditional and new markers of inflammation in patients with sepsis. Clin Chem Lab Med. 1999. 37:363–8.

16.Rau BM., Frigerio I., Büchler MW., Wegscheider K., Bassi C., Puolakkainen PA, et al. Evaluation of procalcitonin for predicting septic multiorgan failure and overall prognosis in secondary peritonitis: a prospective, international multicenter study. Arch Surg. 2007. 142:134–42.

17.Rau B., Krüger CM., Schilling MK. Procalcitonin: improved biochemical severity stratification and postoperative monitoring in severe abdominal inflammation and sepsis. Langenbecks Arch Surg. 2004. 389:134–44.

18.Liaudat S., Dayer E., Praz G., Bille J., Troillet N. Usefulness of procalcitonin serum level for the diagnosis of bacteremia. Eur J Clin Microbiol Infect Dis. 2001. 20:524–7.

19.Whang KT., Steinwald PM., White JC., Nylen ES., Snider RH., Simon GL, et al. Serum calcitonin precursors in sepsis and systemic inflammation. J Clin Endocrinol Metab. 1998. 83:3296–301.

20.Uzzan B., Cohen R., Nicolas P., Cucherat M., Perret GY. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006. 34:1996–2003.

21.Boussekey N., Leroy O., Georges H., Devos P., d'Escrivan T., Guery B. Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit. Infection. 2005. 33:257–63.

22.Thayyil S., Shenoy M., Hamaluba M., Gupta A., Frater J., Verber IG. Is procalcitonin useful in early diagnosis of serious bacterial infections in children? Acta Paediatr. 2005. 94:155–8.

23.Harbarth S., Holeckova K., Froidevaux C., Pittet D., Ricou B., Grau GE, et al. Diagnostic value of procalcitonin, interleukin-6 and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001. 164:396–402.

24.Müller B., Becker KL., Schächinger H., Rickenbacher PR., Huber PR., Zimmerli W, et al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med. 2000. 28:977–83.

25.Povoa P., Almeida E., Moreira P., Fernandes A., Mealha R., Aragao A, et al. C-reactive protein as an indicator of sepsis. Intensive Care Med. 1998. 24:1052–6.

26.Aikawa N., Fujishima S., Endo S., Sekine I., Kogawa K., Yamamoto Y, et al. Multicenter prospective study of procalcitonin as an indicator of sepsis. J Infect Chemother. 2005. 11:152–9.

27.Endo S., Aikawa N., Fujishima S., Sekine I., Kogawa K., Yamamoto Y, et al. Usefulness of procalcitonin serum level for the discrimination of severe sepsis from sepsis: a multicenter prospective study. J Infect Chemother. 2008. 14:244–9.