Procalcitonin
Last updated 7th Feb 2023 - Tom Heaton
Procalcitonin is a test that can be used to guide therapy around bacterial infections.
Physiology
Procalcitonin is an innate biological molecule.
It arises from the larger molecule preprocalcitonin and is the precursor of calcitonin, the thyroid hormone.
It is normally produced in low levels (<0.1ng/ml)
It is usually cleared by the parathyroid gland and with low level of renal clearance.
As well as its calcium effects it has a role in modulating immune function.
This includes:
It arises from the larger molecule preprocalcitonin and is the precursor of calcitonin, the thyroid hormone.
It is normally produced in low levels (<0.1ng/ml)
It is usually cleared by the parathyroid gland and with low level of renal clearance.
As well as its calcium effects it has a role in modulating immune function.
This includes:
- Modulating cytokines
- Augmenting initial migratory effect of monocytes
- Inhibits expression of inducible nitric oxide synthase in vascular smooth muscle (but may augment it in prestimulated cells)
Pathophysiology
In infections (bacterial in particular) it is formed from other tissues of the body in response to bacterial endotoxin or cytokines.
This is particularly the case in neuroendocrine cells of the lungs and digestive tract.
Its synthesis is inhibited by the gamma interferon produced in response to a viral infection.
This rise can be profound after an infective insult.
Typical patterns include:
Of note, PCT may remain low in certain presentations of bacterial infection:
This is particularly the case in neuroendocrine cells of the lungs and digestive tract.
Its synthesis is inhibited by the gamma interferon produced in response to a viral infection.
This rise can be profound after an infective insult.
Typical patterns include:
- Rise 2-4 hours after onset of sepsis
- Peak levels at 24-48h
- Extent of rise correlated with degree of bacterial infection
- Levels halve daily when infection is controlled
Of note, PCT may remain low in certain presentations of bacterial infection:
- Early on infection
- Localised disease
- Immune compromise
False Elevations
There are some conditions that can also elevate procalcitonin without bacterial infection.
These include:
These include:
- Trauma/tissue damage
- Burns
- Rhabdomyolysis
- Tumour lysis
- Major surgery
- Infection
- Invasive fungal disease
- Malaria
- Some severe stress states
- Major multiorgan dysfunction
- Cytokine storm
- Liver dysfunction
- Severe renal dysfunction (particularly with dialysis)
- Cardiac
- Myocardial infarction
- Cardiogenic shock
- Some malignancies e.g. small cell lung cancer
- Some autoimmune disease
- Organ transplant
- T-cell antibody treatment
Clinical Use
The mainstay of its proposed use is as a relatively bacterial specific infection biomarker.
It is described as having better sensitivity and speed of measurement than some other test available (CRP and blood cultures).
As such it could be used to identify bacterial infection when the clinical picture is challenging (occult infection or other inflammatory process likely).
It may also be able to indicate when infections are well controlled and thus when antibiotics could be stopped.
Sensitivity and specificity values of sound 80% have been described, which are clearly far from perfect, meaning some caution remains needed with interpretation.
Different protocols have been described for use.
This can be based on the specific value and the trend.
Threshold for identifying bacterial infection include:
However, it is important to remember that there is a correlation of the PCT value with the disease severity.
As such, its magnitude may be more persuasive than its use with a low level cut off.
A counter to this is that a very negative result has strong sensitivity to exclude bacterial infection.
Some of the evidence base for its use has been a bit contentious and led to varied use.
A single value can be challenging to interpret, so trends over time are generally more valuable.
The ADAPT-Sepsis study is ongoing in its efforts to answer this question.
It is described as having better sensitivity and speed of measurement than some other test available (CRP and blood cultures).
As such it could be used to identify bacterial infection when the clinical picture is challenging (occult infection or other inflammatory process likely).
It may also be able to indicate when infections are well controlled and thus when antibiotics could be stopped.
Sensitivity and specificity values of sound 80% have been described, which are clearly far from perfect, meaning some caution remains needed with interpretation.
Different protocols have been described for use.
This can be based on the specific value and the trend.
Threshold for identifying bacterial infection include:
- >0.25 microgram/L
- >0.5 microgram/L in critically ill patients
However, it is important to remember that there is a correlation of the PCT value with the disease severity.
As such, its magnitude may be more persuasive than its use with a low level cut off.
A counter to this is that a very negative result has strong sensitivity to exclude bacterial infection.
Some of the evidence base for its use has been a bit contentious and led to varied use.
A single value can be challenging to interpret, so trends over time are generally more valuable.
The ADAPT-Sepsis study is ongoing in its efforts to answer this question.
Links & References
- Nickson, C. Procalcitonin. LITFL. 2020. https://litfl.com/procalcitonin/
- AACC. Procalcitonin testing and antibiotic stewardship. Youtube. 2020. https://www.youtube.com/watch?v=E1_F_Z-yYjE
- Wacker, C. et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13(5):426-35. https://www.sciencedirect.com/science/article/pii/S1473309912703237
- Schuetz, P. et al. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 2011; 9: 107. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186747/
- ADAPT-Sepsis. Warwick Clinical Trials Unit. https://warwick.ac.uk/fac/sci/med/research/ctu/trials/adaptsepsis/
