Procalcitonin

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Procalcitonin (PCT) is a precursor of the hormone calcitonin, which is involved with calcium homeostasis, and is produced by the C-cells of the thyroid gland. It is there that procalcitonin is cleaved into calcitonin, katacalcin and a protein residue. It is not released into the blood stream of healthy individuals.

Triggering receptor expressed on myeloid cells-1 (TREM-1) may be a more accurate serum biomarker for diagnosing infection.[1][2]

Procalcitonin is said to distinguish between bacterial and non-bacterial causes of inflammation.[3][4][5] A meta-analysis of three studies, dominated by a pediatric study[6], reported that the sensitivity for differentiating bacterial from viral infections was 92% with specificity of 73%.[7]

Measurement

With the derangements that a severe infection with an associated systemic response brings, the blood levels of procalcitonin may rise to 100 ng/ml. In blood serum, procalcitonin has a half-life of 25 to 30 hours.

There are two commercial kits for measuring the PCT.[8] The Kryptor assay has a lower limit of detection of 0.06 μg/L while the LUMI kit has a lower limit of detection of 0.3–0.5 μg/L. The Kryptor kit is thought by some to be better and more sensitive than the the LUMI test.[8] However, comparisons of their ability to prognosticate pneumomia as compared to using the c-reactive protein have conflicted with PCT by Kryptor being similar to[9] or better than[10] the c-reactive protein and PCT by LUMI being better[11]than the c-reactive protein.

Uses

The role of procalcitonin in the decision to initiate or discontinue antibiotics in acute respiratory tract infections has been reviewed by the Cochrane collaboration. [12]

Diagnosis and prognosis of sepsis

Measurement of procalcitonin can be used as a marker of severe sepsis and generally grades well with the degree of sepsis,[13] although levels of procalcitonin in the blood are very low. PCT has the greatest sensitivity (85%) and specificity (91%) for differentiating patients with SIRS from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha.[14] However, the test is not routinely used and has yet to gain widespread acceptance.

In a comprehensive meta-analysis in 2007 the diagnostic accuracy of procalcitonin as a marker to differentiate sepsis from other non-infectious causes of systemic inflammatory responses was estimated including 18 studies (14 phase 2 and 4 phase 3 studies). [15] In this review the overall diagnostic performance of procalcitonin was low. The authors concluded that procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients and should not be used as often as it is currently done in the critical care setting.

Diagnosis of bacteremia

A meta-analysis reported a sensitivity of 76% and specificity of 70% for the diagnosis of bacteremia.[16]

Critical care

The procalcitonin may reduce antibiotic use in critical care; however, the effect on mortality is not certain.[17]

Prognosis of respiratory tract infection

A randomized controlled trial of patients with respiratory tract infections (more common diagnoses were rhinosinusitis and bronchitis), procalcitonin guided therapy reduces antibiotic use without compromising patient outcome.[18][19][20][21]

Diagnosis of pneumonia

Procalcitonin has been studied for the diagnosis of pneumonia.[22]

Prognosis of pneumonia

A cluster randomized controlled trial found that the procalcitonin level can help guide antibiotic therapy in patients with pneumonia. In this trial, "on the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively".[23]. However, a nonrandomized, observational study reported "limited, prognostic value" of the procalcitonin[11].

Several studies have compared the procalcitonin level to clinical prediction rules, either the pneumonia severity index or the CURB-65, with the following results:

In two trials of using procalcitonin in primary care, Briel[19] and Burkhardt[27] found reduction in antibiotics.

Trails of guiding antibiotic decisions

Various trials have studied this role.[28][29][17][30]

References

  1. Su L, Han B, Liu C, Liang L, Jiang Z, Deng J et al. (2012). "Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study.". BMC Infect Dis 12: 157. DOI:10.1186/1471-2334-12-157. PMID 22809118. PMC PMC3426475. Research Blogging.
  2. Gibot S, Kolopp-Sarda MN, Béné MC, Cravoisy A, Levy B, Faure GC et al. (2004). "Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis.". Ann Intern Med 141 (1): 9-15. PMID 15238365. [e]
  3. Brunkhorst FM, Eberhard OK, Brunkhorst R (1999). "Discrimination of infectious and noninfectious causes of early acute respiratory distress syndrome by procalcitonin.". Crit Care Med 27 (10): 2172-6. PMID 10548201. “Small study with 27 patients with ARDS of known causes”
  4. de Werra I, Jaccard C, Corradin SB, Chioléro R, Yersin B, Gallati H et al. (1997). "Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia.". Crit Care Med 25 (4): 607-13. PMID 9142024. “Thirty-four selected patients; procalcitonin mainly rose in septic shock and not bacterial pneumonia.”
  5. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY (2006). "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 34 (7): 1996-2003. DOI:10.1097/01.CCM.0000226413.54364.36. PMID 16715031. Research Blogging.
  6. Lorrot M, Moulin F, Coste J, Ravilly S, Guérin S, Lebon P et al. (2000). "[Procalcitonin in pediatric emergencies: comparison with C-reactive protein, interleukin-6 and interferon alpha in the differentiation between bacterial and viral infections"]. Presse Med 29 (3): 128-34. PMID 10686961.
  7. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J (2004). "Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis.". Clin Infect Dis 39 (2): 206-17. DOI:10.1086/421997. PMID 15307030. Research Blogging.
  8. 8.0 8.1 Niederman MS (December 2008). "Biological markers to determine eligibility in trials for community-acquired pneumonia: a focus on procalcitonin". Clin. Infect. Dis. 47 Suppl 3: S127–32. DOI:10.1086/591393. PMID 18986278. Research Blogging.
  9. Holm A, Pedersen SS, Nexoe J, et al. (July 2007). "Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care". Br J Gen Pract 57 (540): 555–60. PMID 17727748. PMC 2099638[e]
  10. Müller B, Harbarth S, Stolz D, et al. (2007). "Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia". BMC Infect. Dis. 7: 10. DOI:10.1186/1471-2334-7-10. PMID 17335562. PMC 1821031. Research Blogging.
  11. 11.0 11.1 Brunkhorst FM, Al-Nawas B, Krummenauer F, Forycki ZF, Shah PM (February 2002). "Procalcitonin, C-reactive protein and APACHE II score for risk evaluation in patients with severe pneumonia". Clin. Microbiol. Infect. 8 (2): 93–100. PMID 11952722. [e] Cite error: Invalid <ref> tag; name "pmid11952722" defined multiple times with different content
  12. Schuetz P, Müller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L et al. (2012). "Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.". Cochrane Database Syst Rev 9: CD007498. DOI:10.1002/14651858.CD007498.pub2. PMID 22972110. Research Blogging.
  13. Meisner M, Tschaikowsky K, Palmaers T, Schmidt J (1999). "Comparison of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS" 3 (1): 45-50. PMID 11056723. [e]
  14. BalcI C, Sungurtekin H, Gürses E, Sungurtekin U, Kaptanoglu B (2003). "Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit". Critical care (London, England) 7 (1): 85-90. PMID 12617745. [e]
  15. Tang BM, Eslick GD, Craig JC, McLean AS (2007). "Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis". The Lancet infectious diseases 7 (3): 210-7. DOI:10.1016/S1473-3099(07)70052-X. PMID 17317602. Research Blogging.
  16. Jones AE, Fiechtl JF, Brown MD, Ballew JJ, Kline JA (2007). "Procalcitonin test in the diagnosis of bacteremia: a meta-analysis". Annals of emergency medicine 50 (1): 34-41. DOI:10.1016/j.annemergmed.2006.10.020. PMID 17161501. Research Blogging.
  17. 17.0 17.1 Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C et al. (2010). "Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.". Lancet. DOI:10.1016/S0140-6736(09)61879-1. PMID 20097417. Research Blogging.
  18. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I et al. (2009). "Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial.". JAMA 302 (10): 1059-66. DOI:10.1001/jama.2009.1297. PMID 19738090. Research Blogging.
  19. 19.0 19.1 Briel M, Schuetz P, Mueller B, et al (October 2008). "Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care". Archives of internal medicine 168 (18): 2000–7; discussion 2007–8. DOI:10.1001/archinte.168.18.2000. PMID 18852401. Research Blogging. Cite error: Invalid <ref> tag; name "pmid18852401" defined multiple times with different content
  20. Christ-Crain M, Stolz D, Bingisser R, et al. (July 2006). "Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial". Am. J. Respir. Crit. Care Med. 174 (1): 84–93. DOI:10.1164/rccm.200512-1922OC. PMID 16603606. Research Blogging.
  21. Stolz D, Christ-Crain M, Bingisser R, et al. (January 2007). "Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy". Chest 131 (1): 9–19. DOI:10.1378/chest.06-1500. PMID 17218551. Research Blogging.
  22. Walsh EE, Swinburne AJ, Becker KL, Nylen ES, Snider RH, Baran A et al. (2012). "Can serum procalcitonin levels help interpret indeterminate chest radiographs in patients hospitalized with acute respiratory illness?". J Hosp Med. DOI:10.1002/jhm.1984. PMID 23086568. Research Blogging.
  23. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Müller B (2004). "Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial". Lancet 363 (9409): 600-7. DOI:10.1016/S0140-6736(04)15591-8. PMID 14987884. Research Blogging.
  24. Huang DT, Weissfeld LA, Kellum JA, Yealy DM, Kong L, Martino M et al. (2008). "Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia.". Ann Emerg Med 52 (1): 48-58.e2. DOI:10.1016/j.annemergmed.2008.01.003. PMID 18342993. Research Blogging.
  25. Krüger S, Ewig S, Marre R, Papassotiriou J, Richter K, von Baum H et al. (2008). "Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes.". Eur Respir J 31 (2): 349-55. DOI:10.1183/09031936.00054507. PMID 17959641. Research Blogging.
  26. 26.0 26.1 Menéndez R, Martínez R, Reyes S, Mensa J, Filella X, Marcos MA et al. (2009). "Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia.". Thorax 64 (7): 587-91. DOI:10.1136/thx.2008.105312. PMID 19131448. Research Blogging.
  27. Burkhardt O, Ewig S, Haagen U, Giersdorf S, Hartmann O, Wegscheider K et al. (2010). "Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection.". Eur Respir J 36 (3): 601-7. DOI:10.1183/09031936.00163309. PMID 20185423. Research Blogging.
  28. Shehabi Y, Sterba M, Garrett PM, Rachakonda KS, Stephens D, Harrigan P et al. (2014). "Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. A randomized controlled trial.". Am J Respir Crit Care Med 190 (10): 1102-10. DOI:10.1164/rccm.201408-1483OC. PMID 25295709. Research Blogging.
  29. Oliveira CF, Botoni FA, Oliveira CR, Silva CB, Pereira HA, Serufo JC et al. (2013). "Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial.". Crit Care Med 41 (10): 2336-43. DOI:10.1097/CCM.0b013e31828e969f. PMID 23921272. Research Blogging.
  30. Prkno A, Wacker C, Brunkhorst FM, Schlattmann P (2013). "Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock--a systematic review and meta-analysis.". Crit Care 17 (6): R291. DOI:10.1186/cc13157. PMID 24330744. PMC PMC4056085. Research Blogging.

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