Understanding Procalcitonin

Utilizing the right test for optimal patient outcomes

When a patient presents with signs of infection, a timely diagnosis is essential. This is especially true for patients with severe infections such as LRTIsecondary bacterial infection associated with COVID-19, or sepsis.

It is common to encounter patients who present symptoms—such as cough, shortness of breath, and fever—that can be associated with several different diagnoses (e.g. a case of chronic obstructive pulmonary disease (COPD) exacerbation). One of your first questions will likely be, “Does my patient have a bacterial infection or is there a non-bacterial cause of the current exacerbation?” Followed by, “Does the patient need antibiotics?” 

Whether in the emergency department (ED), intensive care unit (ICU) or another hospital ward, consider ordering a procalcitonin (PCT) test along with other diagnostic tests when a bacterial infection is possible.

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Use of PCT in Patients Presenting with Overlapping Symptoms
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What exactly is PCT? 

PCT is a pro-hormone that is highly sensitive and specific for bacterial infection. PCT provides insights into the risk of a patient having a bacterial infection, as well as the severity of that infection. We’ve shared how PCT can help reduce antibiotic exposure and bolster antibiotic stewardship programsLet’s dive deeper into the science of what PCT is and how it can aid in differentiation between viral and bacterial infections.

 

Understanding the Kinetics of PCT

Discover the unique kinetics of PCT in response to the host response resulting from bacterial infection.

PCT is a protein consisting of 116 amino acids and can be detected in the blood in response to bacterial infection with systemic inflammatory reactions.

Procalcitonin is the precursor protein of the hormone Calcitonin.3 Both PCT and Calcitonin are distinct proteins. 

  • Calcitonin is exclusively produced by C-cells of the thyroid gland in response to hormonal stimuli. It plays an important role in the pathway and regulation of calcium and phosphate in bone metabolism and is the main medullary thyroid carcinoma (MTC) tumor marker.4

In healthy individuals, the prohormone PCT is rapidly processed into the mature hormone calcitonin. Therefore, PCT values in non-infected individuals are very low: < 0.1 µg/L.4

  • In case of bacterial insult, PCT can be induced outside the thyroid gland, in the parenchymal tissue of many organs, and then released into circulation in large amounts4

At first, cytokine-stimulated adherent monocytes release PCT in low quantities (< 2h). While this synthesis is limited, it plays an important role in the initiation of PCT synthesis in storage tissues of humans.4

This PCT burst is initiated in all storage tissues (peak 12-24h). Parenchymal tissue is the most common type of tissue in humans. As a result, extreme concentrations of PCT can be generated (100,000-fold increase in contrast to physiological concentrations).4 The PCT burst continues as long as the stimulus for synthesis exists.4

Additional experiments clarified why PCT is only synthesized during bacterial but not in viral infections. Cells were incubated with IL-1β and INF-γ, inflammatory cytokines known to be released during bacterial and viral infection, respectively. Whereas IL-1ß stimulated the PCT synthesis, the addition of IFN-y blocked this effect.5

The conclusion was that INF-γ, which is produced during viral infection, blocks the pathway for PCT synthesis. These findings led to the explanation of the observed high specificity of PCT for bacterial infection and the utility of this biomarker to differentiate bacterial infections from viral or other, non-bacterial causes of inflammation. 5

 


PCT is the additional piece of information that is available quickly to support clinical assessment. Using PCT to aid personalized antibiotic treatment leads to lower antibiotic exposure.1

 

Baseline PCT testing, in conjunction with clinical signs and symptoms, may tell you if a bacterial infection is likely or not. Initiation of antibiotic treatment depends on the severity of the illness and the patient’s outcome risk. In high-risk patients with severe illness in the ICU, initiation of empiric antibiotic treatment is based on clinical judgment. In patients with mild illness outside the ICU in which bacterial infection is uncertain, baseline PCT can help clinicians decide whether to initiate antibiotics or consider an alternative diagnosis.2 (Keep in mind: It only takes approximately 20 minutes to get results.)

Serial PCT measurements can indicate whether the patient is responding to the antibiotics or you need to consider a course change. PCT levels should be trended every 24 to 48 hours to determine when the infection has resolved enough that antibiotics can be safely stopped. Discontinuing antibiotic treatment can be considered in clinically stable patients when the PCT level has dropped below the respective cut-offs for sepsis or LRTI, or when it has decreased by ≥ 80% of the peak value


There are a situations when PCT levels may appear elevated for reasons not related to an infection.


Want to learn how to interpret PCT results?

Explore specific antibiotic therapy guidelines with PCT values for these conditions:
 

PCT

Important considerations when interpreting PCT results 

PCT levels may not be elevated in patients infected by certain atypical pathogens, such as Chlamydophila pneumoniae and Mycoplasma pneumoniae.6

There are situations and conditions where PCT can be elevated by non-infectious causes. These include, but are not limited to patients:7-10

  • Patients experiencing major trauma and/or recent surgical procedure including extracorporeal circulation or burns;
  • Patients under treatment with OKT3 antibodies, OK-432, interleukins, TNF-alpha and other drugs stimulating the release of pro-inflammatory cytokines or resulting in anaphylaxis;
  • Patients diagnosed with active medullary C-cell carcinoma, small cell lung carcinoma, or bronchial carcinoid;
  • Patients with prolonged or severe cardiogenic shock, prolonged severe organ perfusion anomalies or after resuscitation from cardiac arrest;
  • Patients with acute or chronic viral hepatitis, decompensated severe liver cirrhosis (Child-Pugh Class C) and/or acute liver failure;

  • Patients receiving peritoneal dialysis or hemodialysis treatment;
  • Patients with biliary pancreatitis, chemical pneumonitis or heat stroke;
  • Patients with invasive fungal infections (e.g. candidiasis, aspergillosis ) or acute attacks of plasmodium falciparum malaria;
  • Patients with Kawasaki, Still’s Disease or Bell’s Palsy;
  • Patients with mushroom poisoning;
  • Patients with preeclampsia;
  • Patients with paracetamol intoxication;
  • Also severity of renal failure or insufficiency, may influence procalcitonin values and should be considered as potentially confounding clinical factors when interpreting PCT values.

Low PCT levels do not automatically exclude the presence of bacterial infection. Such low levels may be obtained, e.g., during the early course of infections, in localized infections and in subacute endocarditis. Therefore, follow-up and re-evaluation of PCT in clinical suspicion of infection is pivotal. The PCT measuring technique should be chosen dependent on intended clinical use.

Discover how PCT stands out in comparison to other clinical biomarkers
Learn about how PCT compares to traditional diagnostic tests

Learn more about implementing optimized procalcitonin testing in your hospital.

References
  1. Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018 Jan 1;18(1):95-107. 
  2. Schuetz P, Beishuizen A, Broyles M, Ferrer R, Gavazzi G, Gluck EH, et al. Procalcitonin (PCT)-guided antibiotic stewardship: An international experts consensus on optimized clinical use. Clin Chem Lab Med. 2019 Sep 1;57(9):1308-18. 
  3. Le Moullec JM, Jullienne A, Chenais J, Lasmoles F, Guliana JM, Milhaud G, et al. The complete sequence of human preprocalcitonin. FEBS letters. 1984 Feb 13;167(1):93-7. 
  4. Morgenthaler NG, Struck J, Fischer-Schulz C, Seidel-Mueller E, Beier W, Bergmann A. Detection of procalcitonin (PCT) in healthy controls and patients with local infection by a sensitive ILMA. Clin Lab. 2002 Jan 1;48(5-6):263-70. 
  5. Linscheid P, Seboek D, Nylen ES, Langer I, Schlatter M, Becker KL, et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: A novel product of human adipose tissue. Endocrinology. 2003 Dec 1;144(12):5578-84. 
  6. Krüger S, Welte T. Biomarkers in community-acquired pneumonia. Expert Rev Respir Med. 2012 Apr 1;6(2):203-14. 
  7. Meisner M. Procalcitonin-biochemistry and clinical diagnosis. Dresden (Germany): UNI-MED-Verlag; 2010. 
  8. Meisner M, Tschaikowsky K, Hutzler A, Schüttler J, Schick C. Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med. 1998;24(7):680–4. 
  9. Chiesa C, Panero A, Rossi N, Stegagno M, Giusti MD, Osborn JF, et al. Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis. 1998 Mar 1;26(3):664-72. 
  10. Reith HB, Mittelkötter U, Debus ES, Küssner C, Thiede A. Procalcitonin in early detection of postoperative complications. Dig Surg. 1998;15(3):260-265.