Procalcitonin and Other Biomarkers

Procalcitonin offers unique advantages compared to other common inflammatory markers

When assessing a patient with suspected LRTI, secondary bacterial infections associated with COVID-19 pneumonia, or suspected sepsis, clinicians rely on a number of biomarkers and laboratory tests to make clinical decisions with confidence. Each marker offers its own unique advantages and disadvantages. The sensitivity and specificity for determining bacterial infection and severity is what sets procalcitonin (PCT) apart from the rest. 


PCT stands out in comparision to other biomarkers by offering the following benefits:1

  • High sensitivity and specificity for determining bacterial infection
  • Rapid induction kinetics of 3-6 hours, Levels are not affected by corticosteroids
  • PCT levels increase with higher severity of bacterial infection
  • PCT kinetics reflect response to antibiotic therapy, with a half-life of ~24 hours
  • PCT levels which decline slowly (or not at all) indicate high risk for adverse outcome

 

 

Traditional diagnostic tests used in the context of suspected infection—such as lactate, C-reactive protein, blood cultures, and white blood cell count—may not provide clear indication of bacterial infection. However, the results of these tests can be used alongside PCT testing to create a more defined picture of infection.

Let’s explore how PCT compares to, and complements, each of these biomarkers.

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PCT and lactate

PCT and lactate are important biomarkers that offer information about two different pathophysiological processes. PCT levels indicate the likelihood of a bacterial infection and can help guide decision-making around initiating and discontinuing antibiotic treatment. In contrast, lactate levels reflect the status of tissue perfusion independently of the presence of an infection.

Moreover, while PCT is induced rapidly upon infectious insult, lactate does not rise until late in the course of sepsis.3 As tissue perfusion improves—e.g. due to fluid resuscitation—lactate levels should normalize.

For patients evaluated for a suspected bacterial infection or sepsis, the combination of lactate and PCT measurements—together with clinical data and vital signs—provides complementary information for risk stratification.4
 

Procalcitonin and lactate complementary markers

Hypotension/Shock

PCT

Fluid
Amount/rate 

Infection/Sepsis

Lactate

Antibiotics
Initiation/duration 

PCT’s sensitivity and specificity as a marker of systemic bacterial infection make it a valuable complement to traditional biomarkers used in sepsis risk assessment.8

PCT and C-reactive protein

C-reactive protein (CRP) is also a host response marker. Its secretion is triggered by cytokines in response to acute or chronic inflammation with high sensitivity. However, its specificity for bacterial infection is only moderate and the induction kinetics are slow, with increasing levels only after >12h after causal challenge, reaching peak after 36 to 50 hours .5-7

The long induction time of CRP, its lack of specificity for clinically relevant bacterial infection, and its suppression when corticosteroids are present have reduced its relevance  when it comes to life-saving decision making.8 In contrast, PCT’s rapid induction time of 3-6 hours, its high sensitivity and specificity for systemic bacterial infection, and its decline in response to antibiotic therapy make it a valuable complement to clinical assessment and other biomarkers for sepsis risk assessment and patient management.9


PCT and blood cultures10

Blood cultures are performed to identify bacteria, yeast, or other microorganisms that may be causing a patient’s clinical condition. Physicians then use the information to prescribe targeted treatments. Traditional blood culture takes several days (usually 2-3, but sometimes 10 days or longer, depending on the germ10-12), although more recent methods can provide a result in  several hours.13

Given the slow turnaround time for cultures, physicians  need to prescribe antibiotics empirically, as delaying antibiotic treatment in cases of true bacterial infection may increase the patient’s risk of progressing to a severe disease state. However, this decision comes at the cost of possibly increasing the chances of antibiotic overuse and resistance.

Another challenge with relying on blood cultures is interpreting the result correctly, as blood culture sensitivity is only moderate and may be further decreased in patients already on antibiotics. In addition, there is the potential for false-positive results due to sample contamination. Consequently, it can be difficult to determine whether the bacteria that grew in the culture are the cause of the clinical condition of the patient or not.10-12

With each PCT test taking only 20 minutes, results may be available in just 1-2 hours, especially if the hospital has good logistics in place. This information allows treating physicians to complement their clinical assessment in cases of suspected bacterial infection, including first decisions on the initiation of empiric, broad-spectrum antibiotic therapy. In addition to the PCT test, a blood culture helps identify the pathogen(s) and aid in narrowing the antibiotic spectrum.

During the further treatment course, PCT serial testingcombined with medical history and patient presentation—can be used for monitoring antibiotic treatment efficacy.


PCT and white blood count

The white blood cell (WBC) count is probably the most commonly used biomarker for the consideration of an infection.4 An elevated WBC may be suggestive of an infection but acute trauma, burns, seizures, and some medications also can have a significant effect on the WBC. As a result, WBC offers low infection-specificity.4 This was supported by a study that found that more than 50% of patients diagnosed with sepsis had normal WBC.14


PCT is the biomarker with the highest sensitivity and specificity for bacterial infection when compared to lactate, CRP,14-15 and WBC count.

With the results from a PCT assay, clinicians can better assess the likelihood of bacterial infection and set patients up on a successful course of treatment with either appropriate antibiotics or alternative therapy. 

Discover how to interpret PCT results with confidence
Learn about PCT kinetics and how to interpret results


In seeking the ideal marker or laboratory test for clinically relevant bacterial infection there are several important considerations. The perfect biomarker would:4

  • Have the ability to differentiate bacterial from viral infections or other, non-infectious causes of inflammation
  • Have good positive and negative predictive value
  • Stratify patients as to severity of infection and outcome risk
  • Compliment clinical assessment to support therapeutic decision-making
  • Enable monitoring over the course of the disease and its response to therapy
  • Improve emergency department and hospital resource utilization

PCT meets the criteria listed above. There is no “gold standard” for identifying clinically relevant bacterial infections, but PCT puts us one step closer

Looking for quick, on-the-go guide to PCT levels and result interpretations?
Get the PCT pocket card

Learn more about implementing optimized procalcitonin testing in your hospital.

References
  1. Meisner M. Procalcitonin-biochemistry and clinical diagnosis. Dresden (Germany): UNI-MED-Verlag; 2010.
  2. Reinhart K, Meisner M, Brunkhorst FM. Markers for sepsis diagnosis: What is useful? Crit Care Clin. 2006 Jul 1;22(3):503-19.
  3. Freund Y, Delerme S, Goulet H, Bernard M, Riou B, Hausfater P. Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers. 2012 Nov 1;17(7):590-6.
  4. Blomkalns AL. Sick or not sick?: evolving biomarkers for severe bacterial infection. EMCREG. 2007;7:1-1.
  5. Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest. 1993 Apr 1;91(4):1351-7. 
  6. Pepys MB, Hirschfield GM. C-reactive protein: A critical update. J Clin Invest. 2003 Jun 15;111(12):1805-12.
  7. Standage SW, Wong HR. Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti Infect Ther. 2011 Jan 1;9(1):71-9.
  8. 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.  
  9. Müller B, Becker KL, Schächinger H, Rickenbacher PR, Huber PR, Zimmerli W, et al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med. 2000 Apr 1;28(4):977-83.
  10. Chernecky CC, Berger BJ. Laboratory tests and diagnostic procedures-E-Book. Elsevier Health Sciences. 2012 Oct 31.
  11. Fischbach FT, Dunning MB. A manual of laboratory and diagnostic tests, 8th ed. Lippincott Williams & Wilkins; 2009. 
  12. Pagana KD, Pagana TJ. Mosby's Manual of Diagnostic and Laboratory Tests-E-Book, 4th ed. Elsevier Health Sciences; 2017 Oct 8.
  13. Bloos F, Sachse S, Kortgen A, Pletz MW, Lehmann M, Straube E, et al. Evaluation of a polymerase chain reaction assay for pathogen detection in septic patients under routine condition: An observational study. PloS one. 2012 Sep 27;7(9):e46003.
  14. Seigel TA, Cocchi MN, Salciccioli J, Shapiro NI, Howell M, Tang A, et al. Inadequacy of temperature and white blood cell count in predicting bacteremia in patients with suspected infection. J Emerg Med. 2012 Mar 1;42(3):254-9.
  15. Lee A, Mirrett S, Reller LB, Weinstein MP. Detection of bloodstream infections in adults: How many blood cultures are needed? J Clin Microbiol. 2007 Nov 1;45(11):3546-8.