Procalcitonin

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Procalcitonin
Properties of human protein
Mass / length primary structure 116 amino acids
Identifier
Gene names CALCA  ; CALC1
External IDs
Occurrence
Homology family Calcitonin
Parent taxon Euteleostomi

Procalcitonin ( PCT ) is a precursor of the hormone calcitonin and is produced in the C cells of the thyroid . Under certain circumstances, such as infections or operations , other cells such as liver or fat cells also produce this prohormone . In 2005, the Food and Drug Administration approved PCT in connection with the determination of further laboratory values ​​for the risk assessment of patients critically ill with sepsis . In connection with the fact that every infectious disease is far too complex to be reduced to a single surrogate marker .

Clinical application of PCT

General information on using the PCT

PCT is to be established as a marker for the diagnosis and monitoring of particularly severe bacterial infections. When interpreting the PCT values, however, it should be noted that non-infectious causes can also lead to an increase in PCT in the blood and that low values ​​do not rule out infection or sepsis.

An increase in PCT concentration beyond certain decision limits indicates increased inflammatory activity. The PCT concentration in the blood presumably increases with localized bacterial infections, viral infections, non-infectious inflammatory diseases such as e.g. B. autoimmune processes or after trauma and operations to a lesser extent than in severe bacterial infections and sepsis. Nevertheless, the value ranges of the PCT concentration overlap so clearly in the individual inflammatory conditions that it can sometimes cause problems to find decision limits on the basis of which it is possible to draw diagnostic benefits from the determination of PCT. Larger studies to establish such decision limits for the use of PCT have so far been carried out for the diagnosis of diseases such as sepsis and infections of the deep respiratory tract.

A decrease in the PCT concentration in bacterial infections, e.g. B. under antibiotic therapy, a decrease in inflammatory activity and therapy response, a persistently high or even further increasing concentration is associated with a non-response.

However, the clinical benefit of using PCT for the diagnosis and therapy monitoring of inflammatory diseases remains the subject of current discussions. A disadvantage of the PCT determination is the high cost compared to the classic inflammation parameters .

PCT in sepsis diagnostics

In critically ill patients with symptoms of acute systemic inflammation, it is often difficult to decide whether sepsis or another non-infectious disease ( systemic inflammatory response syndrome , SIRS) is present. However, therapies and the outcome of the disease can differ significantly in patients with and without sepsis. There is therefore a great clinical need for diagnostic possibilities to differentiate between systemic inflammatory response syndrome (SIRS) and severe bacterial infection / sepsis.

PCT levels above 10 ng / ml indicate a high probability of sepsis, but PCT levels below 10 ng / ml do not rule out sepsis in any case. Values> = 2 ng / ml or> = 0.5 ng / ml are also associated to a high degree with sepsis. In newborns, PCT increases physiologically after birth; H. without infection. Therefore, different reference values ​​apply for the first days of life .

How reliably procalcitonin allows a differentiation between sepsis on the one hand and non-infectious systemic-inflammatory conditions on the other is not yet sufficiently established.

It was assumed that the absolute level of PCT concentrations correlates with the severity of the inflammatory reaction and accordingly often differs in patients with systemic inflammatory response syndrome (SIRS), sepsis , severe sepsis and septic shock. As an expression of individually different immune reactions, the PCT concentration in the blood is subject to considerable interindividual fluctuations for the same degree of inflammation.

The diagnostic value of procalcitonin in sepsis is the subject of current scientific discussion.

PCT for respiratory infections

In localized bacterial respiratory tract infections , the PCT levels are significantly lower than in septic infections. In bacterial bronchitis or pneumonia, PCT levels of around 0.25-0.5 ng / ml are often found. Such low measured values ​​can only be recorded with a sensitive PCT determination method. In an intervention study, the PCT-sensitive levels were used to decide whether or not antibiotic therapy was indicated in patients with infections of the lower respiratory tract. The test results are not clearly positive: in some of the cases antibiotics could be saved without having any negative effects on the course of the disease, on the other hand weak results were also described. Furthermore, it was shown that the duration of antibiotic administration could also be shortened.

Increase in PCT due to other cause

Irrespective of the presence of an infectious disease, the PCT can in rare cases be increased due to other causes. After surgery, sepsis, or trauma, there may be an increase in PCT. The same applies to cardiogenic shock or severe pancreatitis . Likewise, the PCT in medullary thyroid cancer or lung cancer can be increased regardless of whether an infection is present.

Monitoring

PCT is also being examined with regard to its usefulness in monitoring the course of infection and in monitoring therapeutic measures. The PCT values ​​can continue to rise up to 24 hours after the start of successful therapy. PCT has an in vivo half-life of 24 hours.

PCT protein and measurement methods

Under normal metabolic conditions , the hormonally active calcitonin is synthesized and secreted in the C cells of the thyroid gland by specific intracellular proteolytic cleavage from the prohormone PCT. However, intact PCT is found in the blood in bacterial infections and sepsis. All organs are considered the synthesis site in the case of bacterial infection. The PCT concentration rises in healthy volunteers 2-3 hours after induction by intravenous administration of lipopolysaccharides and reaches its maximum value after 24 hours. PCT is very stable in vivo and has a half-life of about 24 hours. Also in vitro PCT is very stable, so that no special requirements concerning the pre-analysis or sample storage must be observed. There are several immunassays for the in vitro determination of PCT . PCT can be determined in serum and plasma with all methods . The time to the result is 19 to 90 minutes, depending on the method.

PCT versus CRP

Compared to the C-reactive protein , a frequently used biomarker , a PCT determination enables a better differentiation between viral vs. bacterial infections.

Nevertheless, neither CRP nor PCT seem to be clearly reliable markers for the clinic to differentiate between infectious and non-infectious diseases, since opportunistic germs (bacteria, fungi) can increasingly develop in immunosuppressed patients at any time.

Individual evidence

  1. M. Christ-Crain, D. Stolz, R. Bingisser, C. Müller, D. Miedinger, PR Huber, W. Zimmerli, S. Harbarth, M. Tamm, B. Müller: Procalcitonin guidance of antibiotic therapy in community- acquired pneumonia: a randomized trial. In: American journal of respiratory and critical care medicine. Volume 174, Number 1, July 2006, pp. 84-93, doi : 10.1164 / rccm.200512-1922OC , PMID 16603606 .
  2. AWMF guideline on prevention, diagnosis, therapy and aftercare of sepsis. (PDF) Register number 079 - 001.
  3. BM Tang, GD Eslick et al: Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. In: The Lancet Infectious Diseases . Volume 7, Number 3, March 2007, pp. 210-217, ISSN  1473-3099 . doi: 10.1016 / S1473-3099 (07) 70052-X . PMID 17317602 . (Review).
  4. B. Uzzan, R. Cohen et al: Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. In: Critical care medicine. Volume 34, Number 7, July 2006, pp. 1996-2003. doi: 10.1097 / 01.CCM.0000226413.54364.36 . PMID 16715031 . (Review).
  5. P. Sridharan, RS Chamberlain: The efficacy of procalcitonin as a biomarker in the management of sepsis: slaying dragons or tilting at windmills? in Surg Infect (Larchmt). 14 (6), 2013 Dec, pp. 489-511. doi: 10.1089 / sur.2012.028 . PMID 24274059
  6. ^ Saskia F van Vugt: Use of serum C reactive protein and procalcitonin concentrations. In: BMJ . 346, 2013, p. F2450.
  7. M. Christ-Crain, D. Jaccard-Stolz et al .: Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomized, single-blinded intervention trial. In: The Lancet . Volume 363, Number 9409, February 2004, pp. 600-607. doi: 10.1016 / S0140-6736 (04) 15591-8 . PMID 14987884 .
  8. M. Christ-Crain, D. Stolz et al: Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. In: American journal of respiratory and critical care medicine. Volume 174, Number 1, July 2006, pp. 84-93. doi: 10.1164 / rccm.200512-1922OC . PMID 16603606 .
  9. eis: respiratory tract infection - bacteria or viruses? In: Doctors newspaper. 7 April 2008.
  10. Michael Meisner: Update on Procalcitonin Measurements. In: Annals of Laboratory Medicine. 34, 2014, pp. 263-273, doi : 10.3343 / alm.2014.34.4.263 .
  11. L. Simon, F. Gauvin et al.: Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. In: Clinical Infectious Diseases . Volume 39, Number 2, July 2004, pp. 206-217. doi: 10.1086 / 421997 . PMID 15307030 . (Review).
  12. W. Nargis, M. Ibrahim, BU Ahamed: Procalcitonin versus C-reactive protein: Usefulness as biomarker of sepsis in ICU patient. In: Int J Crit Illn Inj Sci. 4 (3), July 2014, pp. 195-199, ISSN  2229-5151 . doi: 10.4103 / 2229-5151.141356 . PMID 25337480 .

literature

  • M. Assicot, D. Gendrel, H. Carsin, J. Raymond, J. Guilbaud, C. Bohuon: High serum procalcitonin concentrations in patients with sepsis and infection. In: Lancet. 341 (8844), 1993 Feb 27, pp. 515-518; PMID 8094770 .
  • E. Gabler-Sandberger: Procalcitonin. In: Dtsch Arztebl. 94 (11), 1997, pp. A-646-647.