Procalcitonin

Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. It is composed of 116 amino acids and is produced by parafollicular cells (C cells) of the thyroid and by the neuroendocrine cells of the lung and the intestine.

The level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (0.01 µg/L) of clinical assays.[1] The level of procalcitonin rises in a response to a proinflammatory stimulus, especially of bacterial origin. In this case, it is produced mainly by the cells of the lung and the intestine. It does not rise significantly with viral or non-infectious inflammations. With the derangements that a severe infection with an associated systemic response brings, the blood levels of procalcitonin may rise to 100 µg/L. In serum, procalcitonin has a half-life of 25 to 30 hours. Remarkably the high procalcitonin levels produced during infections are not followed by a parallel increase in calcitonin or a decrease in serum calcium levels.

Medical uses

Sepsis

Measurement of procalcitonin can be used as a marker of severe sepsis caused by bacteria and generally grades well with the degree of sepsis,[2] although levels of procalcitonin in the blood are very low. PCT has the greatest sensitivity (85%) and specificity (91%) for differentiating patients with systemic inflammatory response syndrome (SIRS) from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha.[3] Evidence is emerging that procalcitonin levels can reduce unnecessary antibiotic prescribing to people with lower respiratory tract infections.[4] Currently, procalcitonin assays are widely used in the clinical environment.[5]

A meta-analysis reported a sensitivity of 76% and specificity of 70% for bacteremia.[6]

Prognosis of pneumonia

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 μg/L or <0.25 μg/L) or encouraged (≥ 0.5 μg/L or ≥0.25 μg/L), respectively".[7] However, an earlier nonrandomized, observational study reported "limited, prognostic value" of procalcitonin measurement.[8]

Procalcitonin levels may be useful to distinguish bacterial infections from nonbacterial infections. Trials from 2008 and 2009 have shown that they may help guide therapy and reduce antibiotic use, which can help save on cost of antibiotic prescriptions and drug resistance.[4][9]

Kidney disease

Patients with chronic kidney disease and end-stage renal disease are at higher risk for infections, and procalcitonin has been studied in these populations, who often have higher levels. Procalcitonin can be dialyzed, and so levels are dependent upon when patients receive hemodialysis. While there is no formally accepted cutoff value for patients undergoing HD, using a value of greater or equal to 0.5 ng/mL yielded a sensitivity of 97-98% and a specificity of 70-96%.[10]

Research

Excessive overdose on amphetamine or its analogs can induce systemic inflammation; in a case of amphetamine overdose, sans bacterial infection, significant elevations in procalcitonin were observed.[11]

References

  1. ↑ Dandona P, Nix D, Wilson MF, et al. (December 1994). "Procalcitonin Increase after Endotoxin Injection in Normal Subjects". Journal of Clinical Endocrinology and Metabolism. 79 (6): 1605–1608. doi:10.1210/jc.79.6.1605. PMID 7989463.
  2. ↑ 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". Critical Care. 3 (1): 45–50. doi:10.1186/cc306. PMC 29013Freely accessible. PMID 11056723.
  3. ↑ Balci C, Sungurtekin H, Gürses E, Sungurtekin U, Kaptanoğlu B (February 2003). "Usefulness of Procalcitonin for Diagnosis of Sepsis in the Intensive Care Unit". Critical Care. 7 (1): 85–90. doi:10.1186/cc1843. PMC 154110Freely accessible. PMID 12617745.
  4. 1 2 Schuetz P, Christ-Crain M, Thomann R, et al. (September 9, 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): 1059–1066. doi:10.1001/jama.2009.1297. PMID 19738090.
  5. ↑ Yealy DM, Fine MJ (September 9, 2009). "Measurement of Serum Procalcitonin: A Step Closer to Tailored Care for Respiratory Infections?". JAMA. 302 (10): 1115–1116. doi:10.1001/jama.2009.1318. PMID 19738100.
  6. ↑ 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.
  7. ↑ 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-Bandomised, Single-Blinded Intervention Trial". Lancet. 363 (9409): 600–607. doi:10.1016/S0140-6736(04)15591-8. PMID 14987884.
  8. ↑ 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". Clinical Microbiology and Infection. 8 (2): 93–100. doi:10.1046/j.1469-0691.2002.00349.x. PMID 11952722.
  9. ↑ Briel M, Schuetz P, Mueller B, et al. Procalcitonin-Guided Antibiotic Use vs A Standard Approach For Acute Respiratory Tract Infections in Primary Care. Archives of Internal Medicine. Oct 13 2008; 168 (18):2000-2007; discussion 2007-2008.
  10. ↑ Grace, E; Turner, RM (15 December 2014). "Use of Procalcitonin in Patients with Various Degrees of chronic Kidney Disease Including Renal Replacement Therapy". Clinical Infectious Diseases. 59 (12): 1761–1767. doi:10.1093/cid/ciu732. PMID 25228701.
  11. ↑ Lovas A, Agoston Z, Késmárky K, Hankovszky P, Molnár Z (2014). "Extreme Procalcitonin Elevation without Proven Bacterial Infection Related to Amphetamine Abuse". Case Reports in Critical Care. 2014: 179313. doi:10.1155/2014/179313. PMC 4006559Freely accessible. PMID 24826347.

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