Procalcitonin & Sepsis

Using procalcitonin to aid in the diagnosis and monitoring of sepsis 

Sepsis is a life-threatening condition in which a dysregulated host response to infection can result in tissue damage and multiple organ dysfunction.

Symptoms of sepsis may include fever, difficulty breathing, low blood pressure, fast heart rate, and mental confusion. Treatment often includes antibiotics and intravenous fluids.1 The impact of sepsis on certain patient populations such as pediatrics, neonates and geriatrics can vary, making timely and appropriate treatment even more critical.

In 2017, almost half of all global sepsis cases occurred among children, with an estimated 20 million cases and 2.9 million global deaths in children under five years of age.1

Diagnosis of systemic bacterial infection/sepsis3-6

*PCT levels < 0.5 μg/L do not exclude an infection, localized infections (without systemic signs) may be associated with such low levels.

Reference range: In apparently healthy people, plasma PCT concentrations are found to be > 0.1 μg/L

PCT Levels must always be interpreted in the context of laboratory findings and clinical assessments

Aiding differential diagnosis3,4,5,6

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PCT insight for likelihood of bacterial infection and risk for progression to sepsis or septic shock

PCT levels > 2.0 µg/L indicate a high probability of systemic bacterial infection and risk for progression to sepsis or septic shock. PCT levels < 0.5 µg/L indicate a low likelihood systemic bacterial infection and low risk of progression to sepsis or septic shock. Note: These cut-offs differ from those for patients with acute lower respiratory tract infections (LRTIs).

Trending PCT levels may help determine if the patient status is improving or declining. It is important to measure PCT levels at the first sign of infection to help determine both severity of illness and adequacy of source control.  


 

 

  • PCT levels below 0.5µg/L do not exclude an infection, because localized infections (without systemic signs) may also be associated with such low levels. In addition, if the PCT measurement is done very soon after the systemic infection process has started (usually <6 hours), values may still be low.
  • The PCT reference ranges are valuable guidelines for the clinician but they should always be interpreted in the context of the patient’s clinical condition. Antibiotic treatment should be started or continued on suspicion of infection, particularly in high-risk patients.

*PCT values may be elevated in certain medical conditions independent of bacterial infection. Decisions regarding antibiotic therapy should NOT be based solely on procalcitonin concentrations.

Helpful resources

 

 

PCT insight for safely discontinuing antibiotics

Paired with clinical assessment, B·R·A·H·M·S PCT™ is the only FDA-cleared PCT and CE-certified assay to aid in decision-making on antibiotic discontinuation for patients recovering from suspected or confirmed sepsis.7 The Surviving Sepsis Guidelines suggest that PCT levels can be used to support the discontinuation of empiric antibiotics in patients who initially appeared to have sepsis, but subsequently have limited clinical evidence of infection.8

 

 

 

Aiding assessment of mortality risk

Clinicians can use serial PCT measurements, taken over consecutive days, to help them assess the response to antibiotic therapy and the risk of all-cause mortality among ICU patients. When the infection is controlled, PCT will rapidly decline daily.20 If the PCT level has not significantly declined, the patient and antibiotic therapeutic approach should be reassessed.

A baseline PCT measurement > 2.0 µg/L on Day 0 is an additional risk factor to consider when evaluating procalcitonin measurements on subsequent days.21

 

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PCT and sepsis guidelines
 

1. Surviving Sepsis Campaign Guidelines

The Surviving Sepsis Campaign (SSC) is a global initiative to bring together professional organizations to improve the treatment of sepsis and reduce the high mortality rate associated with the condition. In the 2016 guidelines, the coalition suggested that:8

  • Measurement of PCT levels can be used to support shortening the duration of antibiotic therapy in sepsis patients.8
  • PCT levels can be used to support the discontinuation of empiric antibiotics in patients who initially appeared to have sepsis, but subsequently have limited clinical evidence of infection.8
2. Second World Health Organization (WHO) Model List of Essential In Vitro Diagnostics

The WHO recognizes that in vitro diagnostics (IVDs) are essential for advancing universal health coverage, addressing health emergencies, and promoting healthier populations—the three strategic priorities of the Thirteenth WHO General Programme of Work, 2019-2023.22

  • Recommendation: PCT to guide antibiotic therapy or discontinuation in sepsis and lower respiratory tract infection (for use only in tertiary care facilities and above)22

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References
  1. Mayo Clinic. Sepsis [Internet]. Rochester (MN). [updated 2018 Nov 16; cited 2020 Dec10]. Available here.
  2. Brunkhorst FM, Heinz U, Forycki ZF. Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med. 1998 Aug;24(8):888-889.
  3. 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.
  4. 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. Critical Care Medicine 2000 Apr 1;28(4):977-83.
  5. Meisner M. Procalcitonin-biochemistry and clinical diagnosis. Dresden (Germany): UNI-MED-Verlag; 2010.
  6. 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.
  7. 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.
  8. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar 1;43(3):304-77.
  9. Schuetz P, Christ-Crain M, Thomann R. 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.
  10. Briel M, Schuetz P, Mueller B, Young J, Schild U, Nusbaumer C, et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008 Oct 13;168(18):2000-7.
  11. Burkhardt O, Ewig S, Haagen U, Giersdorf S, Hartmann O, Wegscheider K, et al. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J. 2010 Sep 1;36(3):601-7.
  12. Christ-Crain M, Stolz D, Bingisser R, Müller CH, Miedinger D, Huber PR, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006 Jul 1;174(1):84-93.
  13. Hochreiter M, Köhler T, Schweiger AM, Keck FS, Bein B, von Spiegel T, et al. Procalcitonin to guide duration of antibiotic therapy in surgical intensive care patients: A randomized prospective controlled trial. Crit Care. 2009. Jun;13(3):1-7.
  14. Kristoffersen KB, Søgaard OS, Wejse C, Black FT, Greve T, Tarp B, et al. Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission–a randomized trial. Clin Microbiol Infect. 2009 May; 15(5): 481-7.
  15. Long W, Deng X, Zhang YU, Lu G, Xie J, Tang J. Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia. Respirology. 2011 Jul; 16(5): 819-24.
  16. Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Resp Crit Care Med. 2008 Mar 1;177(5):498-505.
  17. Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, et al. Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: Results of a prospective randomized study. Langenbecks Arch Surg. 2009 Mar 1;394(2):221-6.
  18. Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Müller C, et al. guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis procalcitonin-guidance with standard therapy. Chest. 2007 Jan 1;131(1):9-19.
  19. Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: A randomised study. Eur Respir J. 2009 Dec 1;34(6):1364-75.
  20. Soni NJ, Samson DJ, Galaydick JL, Vats V, Huang ES, Aronson N, et al. Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis. J Hosp Med. 2013 Sep;8(9):530-40.
  21. Second WHO Model List of Essential In Vitro Diagnostics [Internet]. World Health Organization. World Health Organization; 2020 [cited 2020Dec21]. Available here.
  22. Thermo Fisher Scientific. B·R·A·H·M·S GmbH, B·R·A·H·M·S PCT sensitive KRYPTOR® Instruction for Use (Version 19.0us) [Internet]. 2018. Available here.
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