Interpreting Procalcitonin Results

Understanding the kinetics of procalcitonin enables clinicians to receive timely insights

When using procalcitonin (PCT) assays to support clinical decisions, speed and accuracy counts. That’s where PCT kinetics come into play—one factor that makes PCT unique from other conventional inflammatory markers. Unlike other tests, PCT provides timely information specific to systemic bacterial infection, with respect to its presence, course, and severity.1 For example, after a bacterial insult, cytokine IL-6  rises and falls too quickly, whereas C- reactive protein (CRP) levels rise much later and decline much slower than the actual resolution of the episode. PCT, on the other hand, is subject to stimulation by competing causes of inflammation to a lesser degree than other biomarkers.2

Serial PCT testing provides valuable information regarding patient response to treatment and outcome risk.3

PCT levels over the course of an infection

Healthy subjects/non-infected patient: < 0.1 µg/L4


Critically ill patients with a PCT > 2.0 µg/L have a high risk of progression to sepsis or septic shock.5-7


In the presence of a bacterial infection, PCT levels will begin to increase in the first 3 to 6 hours after the onset of infection. The levels will continue to rise rapidly, reaching a peak at 12 to 24 hours. The half-life of PCT is approximately 24 hours.5


 

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Tracking PCT kinetics

PCT has prognostic implications, with higher levels correlating to severity of infection and rapidly declining levels after treatment indicating a positive prognosis.3

Assessing PCT trend over time provides another key insight: patients whose PCT levels fail to decline under treatment may face therapeutic failure and increased mortality risk.6

In particular, it was demonstrated that PCT levels that decline less than 80% from the baseline within four days are associated with increased all-cause 28-day mortality—especially when the baseline PCT measurement is > 2.0 µg/L.

Daily variations of PCT levels during ICU hospitalization in patients admitted with sepsis and septic shock that survived or did not survive.6
Unique kinetics of PCT are strong indicators of mortality risk over time3



Unique kinetics of PCT are strong indicators of patients’ response to antibiotic therapy.3


PCT kinetics and antibiotic decisions

PCT kinetics also lead to greater insights around antibiotic therapy decision-making. Because PCT blood levels rise within 3 to 6 hours after bacterial infection, the levels mirror the host response and severity of infection. Once infection is controlled and the patient is adequately responding to antibiotics, PCT levels decrease by about 50% per day.8

In LRTI patients, when the PCT levels have decreased to < 0.25 µg/L, or ≥ 80% below the peak value, it appears to be acceptable and safe to stop antibiotic therapy, assuming patients also show a favorable clinical response.9,10

Similarly, in patients with suspected or confirmed sepsis, when PCT levels have decreased to < 0.5 µg/L, or > 80% below the peak value, stopping antibiotic therapy appears to be safe and acceptable, assuming patients also show a favorable clinical response.9,10

 

It is important to note that if PCT levels do not decrease by more than 80% at Day 4 of a patient’s illness, treatment failure should be considered and patient re-assessment is recommended.11 Using PCT to decide when to stop antibiotics has been shown to reduce total antibiotic usage and decrease the duration of antibiotic therapy.12

PCT in current practice

While other biomarkers have been used to target the use of antibiotics, improve clinical outcomes, and lower costs, their impact has been limited. In contrast, the inclusion of PCT in antimicrobial stewardship is a game-changer. But it’s not enough to understand the kinetics of PCT—you need to see for yourself what PCT can do for your antibiotic administration, your patients, and your bottom line.

 

 

See how PCT monitoring can offer insights for patient assessment and therapeutic decision making:
 

 


 

 

 

Antibiotic therapy should be considered regardless of PCT result if the patient exhibits one of the following:13

  • Clinically unstable
  • At high risk for adverse outcome
  • Strong evidence of bacterial pathogen
  • The clinical context indicates antibiotic therapy is warranted

 

If antibiotics are withheld, reassess the patient if symptoms persist or worsen and repeat PCT measurement within 6 to 24 hours. To assess treatment success and to support a decision to discontinue antibiotic therapy, follow up tests should be performed once every 1 to 2 days, based upon physician discretion in considering the patient’s evolution and progress.13 Note that PCT levels may not be elevated in patients infected by certain atypical pathogens, such as Chlamydophila pneumoniae and Mycoplasma pneumoniae.14


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References
  1. Karzai W, Oberhoffer M, Meier-Hellmann A, Reinhart K. Procalcitonin—a new indicator of the systemic response to severe infections. Infection. 1997 Nov 1;25(6):329-34.
  2. Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta. 2002 Sep 1;323(1-2):17-29.
  3. Schuetz P, Birkhahn R, Sherwin R, Jones AE, Singer A, Kline JA, et al. Serial procalcitonin predicts mortality in severe sepsis patients: Results from the multicenter procalcitonin MOnitoring SEpsis (MOSES) study. Crit Care Med. 2017 May;45(5):781.
  4. Wiedermann FJ, Kaneider N, Egger P, Tiefenthaler W, Wiedermann CJ, Lindner KH, et al. Migration of human monocytes in response to procalcitonin. Crit Care Med. 2002 May 1;30(5):1112-7.
  5. Meisner M. Procalcitonin-biochemistry and clinical diagnosis. Dresden (Germany): UNI-MED-Verlag; 2010.
  6. Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001 Aug 1;164(3):396-402.
  7. 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.
  8. Meisner M. Procalcitonin: Experience with a new diagnostic tool for bacterial infection and systemic inflammation. J Lab Med. 1999;23:263–72.
  9. Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): A multicentre randomised controlled trial. Lancet Infect Dis. 2010 Feb 6;375(9713):463-74.
  10. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009 Sep 9;302(10):1059-66.
  11. Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011 Aug 8;171(15):1322-31.
  12. de Jong E, van Oers J, Beishuizen A, Vos P, Vermeijden W, Haas L, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: A randomised, controlled, open-label trial. Lancet Infect Dis. 2016 Jul 1;16(7):819-27.
  13. Schuetz P, Raad I, Amin DN. Using procalcitonin-guided algorithms to improve antimicrobial therapy in ICU patients with respiratory infections and sepsis. Curr Opin Crit Care. 2013 Oct;19(5):453-60. doi: 10.1097/MCC.0b013e328363bd38. PMID: 23817026.
  14. Krüger S, Welte T. Biomarkers in community-acquired pneumonia. Expert Rev Respir Med. 2012 Apr 1;6(2):203-14.