Procalcitonin

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Robert G. Badgett, M.D. [2]

Overview

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. 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.

The test is commercially available and produced by Thermo Fisher Scientific.

Triggering receptor expressed on myeloid cells-1 (TREM1) may be a more accurate serum biomarker for diagnosing infection.[1][2]

Comparisons of the procalcitonin and c-reactive protein give conflicting results.[3][4]

Uses

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,[3] although levels of procalcitonin in the blood are very low. In a cross-sectional study 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.[4] However, the test is not routinely used and has yet to gain widespread acceptance.

A review for diagnosing sepsis in 2013 of 30 studies:[5]

  • Sensitivity 77% (95% CI 72% - 81%)
  • Specificity 79% (95% CI 74% – 84%)


A review for diagnosing sepsis in 2007 of 18 studies:[6]

  • Sensitivity 71% (95% CI 67–76)
  • Specificity 71% (95% CI 67–76)


Subsequent meta-analyses have summarized the relevant studies for diagnosing sepsis among immunocompromised patients[7].

Diagnosis of bacteremia

Meta-analyses are available.[8] A meta-analysis reported a sensitivity of 76% and specificity of 70%.[9]

Diagnosis of bacteremia in the elderly has been studied.[10]

  • Sensitivity 96%
  • Specificity 68%


PCT chart. Data from Ratzinger. Biomarkers and PCT in neutropenic patients DTA. Eur J Clin Invest. 2015 PMID 26046926.png

Diagnosis of bacteremia in the neutropenic patients with Systemic inflammatory response syndrome (SIRS) suggests lower sensitivity and higher specificity due to lower PCT levels in neutropenic patients.[3]

Prognosis of pneumonia

Various algorithms for interpreting and responding to the procalcitonin level are available[11].

A cluster randomized trial found that the procalcitonin level can help guide antibiotic therapy. 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".[12]. However, a nonrandomized, observational study reported "limited, prognostic value" of the procalcitonin[13].

Procalcitonin has been used in prediction of mortality in community-acquired pneumonia:[14]

  • Sensitivity 35%
  • Specificity 92%

Guiding antibiotic therapy

Subjects with sepsis

Low quality evidence suggests that PCT-guided therapy may aid antimicrobial stewardship without change in mortality.[15] However, the results of trials are heterogeneous and in most trials, the quality of care in the control group [had not been optimized].

An earlier systematic review by the Cochrane Collaboration concluded that among subjects whose care was guided by procalcitonin "antibiotic consumption was significantly reduced".[16] The first author of this analysis receives financial support from the manufacturer of the procalctonin test.[17]

Subjects with lower respiratory tract infection

PCT-guided therapy does not reduce mortality.[18] An earlier meta-analysis by the Cochrane Collaboration concluded that mortality is reduced[19].

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. PMC 3426475Freely accessible. PMID 22809118. doi:10.1186/1471-2334-12-157. 
  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. 
  3. 3.0 3.1 Ratzinger F, Schuardt M, Eichbichler K, Tsirkinidou I, Bauer M, Haslacher H; et al. (2013). "Utility of sepsis biomarkers and the infection probability score to discriminate sepsis and systemic inflammatory response syndrome in standard care patients.". PLoS One. 8 (12): e82946. PMC 3859603Freely accessible. PMID 24349403. doi:10.1371/journal.pone.0082946. 
  4. Ryu JA, Yang JH, Lee D, Park CM, Suh GY, Jeon K; et al. (2015). "Clinical Usefulness of Procalcitonin and C-Reactive Protein as Outcome Predictors in Critically Ill Patients with Severe Sepsis and Septic Shock.". PLoS One. 10 (9): e0138150. PMC 4569178Freely accessible. PMID 26367532. doi:10.1371/journal.pone.0138150. 
  5. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P (2013). "Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis.". Lancet Infect Dis. 13 (5): 426–35. PMID 23375419. doi:10.1016/S1473-3099(12)70323-7. 
  6. Tang BM, Eslick GD, Craig JC, McLean AS (2007). "Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis.". Lancet Infect Dis. 7 (3): 210–7. PMID 17317602. doi:10.1016/S1473-3099(07)70052-X. 
  7. Bele N, Darmon M, Coquet I, Feugeas JP, Legriel S, Adaoui N; et al. (2011). "Diagnostic accuracy of procalcitonin in critically ill immunocompromised patients.". BMC Infect Dis. 11: 224. PMC 3170614Freely accessible. PMID 21864380. doi:10.1186/1471-2334-11-224. 
  8. Hoeboer SH, van der Geest PJ, Nieboer D, Groeneveld AB (2015). "The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis.". Clin Microbiol Infect. 21 (5): 474–81. PMID 25726038. doi:10.1016/j.cmi.2014.12.026. 
  9. 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. PMID 17161501. doi:10.1016/j.annemergmed.2006.10.020. 
  10. Lai CC, Chen SY, Wang CY, Wang JY, Su CP, Liao CH; et al. (2010). "Diagnostic value of procalcitonin for bacterial infection in elderly patients in the emergency department.". J Am Geriatr Soc. 58 (3): 518–22. PMID 20163483. doi:10.1111/j.1532-5415.2010.02730.x. 
  11. Schuetz P, Bolliger R, Merker M, Christ-Crain M, Stolz D, Tamm M; et al. (2018). "Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials.". Expert Rev Anti Infect Ther. PMID 29969320. doi:10.1080/14787210.2018.1496331. 
  12. 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. PMID 14987884. doi:10.1016/S0140-6736(04)15591-8. 
  13. Brunkhorst FM, Al-Nawas B, Krummenauer F, Forycki ZF, Shah PM (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. 
  14. 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. PMC 2775454Freely accessible. PMID 18342993. doi:10.1016/j.annemergmed.2008.01.003. 
  15. openMetaAnalysis Contributors. Procalcitonin guided antibiotics for severe sepsis and septic shock: a living systematic review. GitHub. Available at https://openmetaanalysis.github.io/Procalcitonin-guided-antibiotics-for-severe-sepsis-and-septic-shock/. Accessed November 28, 2016.
  16. 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. PMID 22972110. doi:10.1002/14651858.CD007498.pub2.  Review in: Ann Intern Med. 2013 Feb 19;158(4):JC5
  17. Schuetz P, Briel M, Christ-Crain M, Stolz D, Bouadma L, Wolff M; et al. (2012). "Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis.". Clin Infect Dis. 55 (5): 651–62. PMC 3412690Freely accessible. PMID 22573847. doi:10.1093/cid/cis464. 
  18. openMetaAnalysis Contributors. Data-only living review: lower respiratory tract infection treatment guided by procalcitonin . GitHub. Available at https://github.com/openMetaAnalysis/Lower-respiratory-tract-infection-treatment-guided-by-procalcitonin. Accessed November 9, 2017.
  19. Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M; et al. (2017). "Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.". Lancet Infect Dis. PMID 29037960. doi:10.1016/S1473-3099(17)30592-3. 

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