Clinical Utility of Procalcitonin (PCT)

brahms pct procalcitonin clinical utilityWhat is Procalcitonin (PCT)?

Procalcitonin helps to differentiate bacterial from viral infections or other causes of systemic inflammation Ref-1. The early detection of elevated PCT levels in patients with suspected bacterial infections enables a more targeted antibiotic treatment. B·R·A·H·M·S PCT-based algorithms have been developed and clinically validated to support informed decisions on when to continue or stop antibiotics, improving patient care and decreasing antibiotic misuse and resistance Ref-2.

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(Pro)Calcitonin synthesis in healthy and infected subjects

Procalcitonin (PCT) is the prohormone of the hormone calcitonin, but procalcitonin and calcitonin are distinct proteins. Calcitonin is exclusively produced by C-cells of the thyroid gland in response to hormonal stimuli. In contrast, after bacterial insult PCT gets induced in many organs via stimulation of the inflammatory cascade and is subsequently released into the circulation where it can reach levels of more than 1000 µg/L. Unlike CRP or IL-6, PCT is not influenced by corticosteroid treatment. Ref-1

 

(pro)Calcitonin Synthesis Release occurs in the form of the posttranslational processed hormone Calcitonin

(pro)Calcitonin Synthesis

Release occurs in the form of the posttranslational processed hormone Calcitonin

A) Procalcitonin in healthy persons Ref-3,4:

In healthy subjects Procalcitonin (PCT) is only an intermediate product in the calcitonin synthesis which is immediately processed to calcitonin. Therefore the PCT levels in non-infected persons are very low Ref-5.

Procalcitonin Synthesis Procalcitonin induction process in bacterial and viral infection

Procalcitonin Synthesis

Procalcitonin induction process in bacterial and viral infection

B) Procalcitonin in infected patients Ref-3,4:

In patients with bacterial infection PCT is rapidly induced in almost every organ and released into circulation.
In viral infections the procalcitonin induction is blocked by IFNγ and PCT levels remain low.

 

Normal values and clinical cut-offs of Procalcitonin Ref-1,2

Reference individuals without bacterial infection usually have PCT levels <0.05 µg/L (97.5 percentile) when measured with an ultrasensitive test Ref-5 and are found clearly below 0.1 µg/L when measured with any of the currently available sensitive B·R·A·H·M·S PCT tests used in clinical routine.
Various clinical cut-offs for PCT are established based on B·R·A·H·M·S PCT assays for a variety of clinical settings, with higher cutoffs being used in critical care and sepsis and lower cutoffs being used in immunocompromised patients, in milder infections and in outpatients.

 

Rapid induction of Procalcitonin (PCT) helps to rapidly identify bacterial infection and sepsis Ref-1

One major advantage of Procalcitonin compared to other parameters is its early and highly specific increase in response to bacterial infection and sepsis which allow both early detection of bacterial infection as well as the monitoring of the response to therapy and the course of disease.
PCT increase in the circulation is measurable after 3-4 hours after the bacterial insult and reaches its peak after 12-24 hours.

kinetics-procalcitonin-pctKinetics of Procalcitonin (PCT) compared to other inflammatory markers upon infection (after Ref-1 Ref-6 Ref-7 Ref-8)

 

When no further stimulation takes place and infection is under control, the procalcitonin levels decline with a half life time of approx. 24 hours. This facilitates the use of PCT monitoring to assess response to AB therapy.

procalcitonin-pct-serum-levelTypical course of PCT serum level according to patient’s response to antibiotic treatment (n=109) Ref-9

 

Stability and half-life time of Procalcitonin (PCT) Ref-1

Procalcitonin is a stable protein in plasma and blood samples. At room temperature, more than 80% of the initial concentrations can be recovered after 24 hours of storage, and >90% is recovered when the sample is kept at 4°C. Plasma PCT has a normal half life of 25–30 hours, and 30–45 hours in patients with severe renal dysfunction.

Caveats: Elevated Procalcitonin (PCT) levels in patients without sepsis or bacterial infection Ref-1

A significant elevation of plasma procalcitonin is found during clinically significant bacterial infection, but particularly during the early days of severe sepsis and septic shock. In patients with non-bacterial “SIRS”, PCT levels are usually found to be in the lower range. However, early after multiple trauma or major surgery, in severe burns or in neonates, procalcitonin levels can be temporarily elevated independently of an infectious process. The return to baseline is usually rapid and in these cases a second increase of PCT can be interpreted as the development of a sepsis episode. Viral infections, bacterial colonisation, localised infections, allergic disorders, autoimmune diseases, and transplant rejection do not usually induce a significant procalcitonin response (values <0.5 μg/L).

References:

Ref-1: Meisner M., Procalcitonin – Biochemistry and Clinical Diagnosis, ISBN 978-3-8374-1241-3, UNI-MED, Bremen 2010

Ref-2: Schuetz P. Et al., EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 017

Ref-3: Linscheid P. et al., Endocrinology 2003

Ref-4: Müller B. et al., JCEM 2001

Ref-5: Morgenthaler N. et al., Clin Lab 2002, 48: 263-270

Ref-6: Brunkhorst FM et al. Intensive Care Medicine 1998, 24: 888-892

Ref-7: Dandona P, J. Clin. Endocrinol. Metab. 1994, 79: 1605-1608

Ref-8: Harbarth S et al. Am J Respir Crit Care Med 2001, 164: 396-402

Ref-9: Stüber F, 21st Int. Congress of Intensive Care and Emergency Medicine (ISICEM), Brussels 2001

 

 

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