Skip to main content

Procalcitonin and Other Host-Response-Based Biomarkers for Evaluation of Infection and Guidance of Antimicrobial Treatment

  • Chapter
  • First Online:
Advanced Techniques in Diagnostic Microbiology

Abstract

Sepsis, the body’s overwhelming response to systemic infections, has the potential to cause organ failure and is responsible for significant morbidity, mortality, and financial burden. Pathogens and their antigens stimulate pro- and anti-inflammatory mediators and immune markers that constitute the host defence and orchestrate leukocyte recruitment to the site of acute infection. Multiple immune and host-response markers have been studied in relation to sepsis for their diagnostic and/or prognostic utility. Recent studies have provided strong evidence that specific immune and host-response markers facilitate early recognition of sepsis, enable assessment of its severity, and provide guidance regarding therapeutic decisions in individual patients. This may allow for a transition from bundled, non-specific infection management involving protocols that combine several medical practices to more individualized management based on the clinical profile of each patient. Specifically, clinical trial data have shown that the host-response marker procalcitonin facilitates improved patient management given that its levels correlate with risk and severity of bacterial infections and can be used to guide therapeutic decisions pertaining to initiation and withdrawal of antimicrobial therapy. The use of procalcitonin and other host-response markers in conjunction with careful clinical assessment of a patient can improve management of infectious diseases by more appropriately tailoring the type and duration of treatment to address each patient’s unique therapeutic needs to ultimately achieve speedy resolution of the illness.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Schuetz P, Christ-Crain M, Muller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections—hope for hype? Swiss Med Wkly. 2009;139(23–24):318–26.

    CAS  PubMed  Google Scholar 

  2. Schutz P, Bally M, Stanga Z, Keller U. Loss of appetite in acutely ill medical inpatients: physiological response or therapeutic target? Swiss Med Wkly. 2014;144:w13957.

    PubMed  Google Scholar 

  3. Schuetz P, Wolbers M, Christ-Crain M, Thomann R, Falconnier C, Widmer I, Neidert S, Fricker T, Blum C, Schild U, et al. Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections. Crit Care. 2010;14(3):R106.

    Article  Google Scholar 

  4. Mitsuma SF, Mansour MK, Dekker JP, Kim J, Rahman MZ, Tweed-Kent A, Schuetz P. Promising new assays and technologies for the diagnosis and management of infectious diseases. Clin Infect Dis. 2013;56(7):996–1002.

    Article  CAS  Google Scholar 

  5. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801–10.

    Article  CAS  Google Scholar 

  6. Vincent JL. Dear SIRS, I’m sorry to say that I don’t like you. Crit Care Med. 1997;25(2):372–4.

    Article  CAS  Google Scholar 

  7. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13(5):426–35.

    Article  CAS  Google Scholar 

  8. Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro-versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000;181(1):176–80.

    Article  CAS  Google Scholar 

  9. Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M. Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med. 2006;34(10):2596–602.

    Article  CAS  Google Scholar 

  10. Schuetz P, Mueller B, Trampuz A. Serum procalcitonin for discrimination of blood contamination from bloodstream infection due to coagulase-negative staphylococci. Infection. 2007;35(5):352–5.

    Article  CAS  Google Scholar 

  11. van Nieuwkoop C, Bonten TN, van’t Wout JW, Kuijper EJ, Groeneveld GH, Becker MJ, Koster T, Wattel-Louis GH, Delfos NM, Ablij HC, et al. Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study. Crit Care. 2010;14(6):R206.

    Article  Google Scholar 

  12. Muller F, Christ-Crain M, Bregenzer T, Krause M, Zimmerli W, Mueller B, Schuetz P. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest. 2010;138(1):121–9.

    Article  CAS  Google Scholar 

  13. Pecile P, Miorin E, Romanello C, Falleti E, Valent F, Giacomuzzi F, Tenore A. Procalcitonin: a marker of severity of acute pyelonephritis among children. Pediatrics. 2004;114(2):e249–54.

    Article  Google Scholar 

  14. Drozdov D, Schwarz S, Kutz A, Grolimund E, Rast AC, Steiner D, Regez K, Schild U, Guglielmetti M, Conca A, et al. Procalcitonin and pyuria-based algorithm reduces antibiotic use in urinary tract infections: a randomized controlled trial. BMC Med. 2015;13(1):104.

    Article  Google Scholar 

  15. Knudsen JB, Fuursted K, Petersen E, Wierup P, Molgaard H, Poulsen SH, Egeblad H. Procalcitonin in 759 patients clinically suspected of infective endocarditis. Am J Med. 2010;123(12):1121–7.

    Article  CAS  Google Scholar 

  16. Mueller C, Huber R, Laifer G, Mueller B, Buerkle G, Perruchoud AP. Procalcitonin and the early diagnosis of infective endocarditis. Circulation. 2004;109:1707–10.

    Article  CAS  Google Scholar 

  17. Schuetz P, Daniels LB, Kulkarni P, Anker SD, Mueller B. Procalcitonin: a new biomarker for the cardiologist. Int J Cardiol. 2016;223:390–7.

    Article  Google Scholar 

  18. Vikse J, Henry BM, Roy J, Ramakrishnan PK, Tomaszewski KA, Walocha JA. The role of serum procalcitonin in the diagnosis of bacterial meningitis in adults: a systematic review and meta-analysis. Int J Infect Dis. 2015;38:68–76.

    Article  CAS  Google Scholar 

  19. Wei TT, Hu ZD, Qin BD, Ma N, Tang QQ, Wang LL, Zhou L, Zhong RQ. Diagnostic accuracy of procalcitonin in bacterial meningitis versus nonbacterial meningitis: a systematic review and meta-analysis. Medicine. 2016;95(11):e3079.

    Article  Google Scholar 

  20. Hugle T, Schuetz P, Mueller B, Laifer G, Tyndall A, Regenass S, Daikeler T. Serum procalcitonin for discrimination between septic and non-septic arthritis. Clin Exp Rheumatol. 2008;26(3):453–6.

    CAS  PubMed  Google Scholar 

  21. Sakr Y, Sponholz C, Tuche F, Brunkhorst F, Reinhart K. The role of procalcitonin in febrile neutropenic patients: review of the literature. Infection. 2008;36(5):396–407.

    Article  CAS  Google Scholar 

  22. Muller B, Peri G, Doni A, Perruchoud AP, Landmann R, Pasqualini F, Mantovani A. High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration. J Leukoc Biol. 2002;72(4):643–9.

    CAS  PubMed  Google Scholar 

  23. de Kruif MD, Lemaire LC, Giebelen IA, Struck J, Morgenthaler NG, Papassotiriou J, Elliott PJ, van der Poll T. The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med. 2008;34(3):518–22.

    Article  Google Scholar 

  24. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004;363(9409):600–7.

    Article  CAS  Google Scholar 

  25. Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84–93.

    Article  CAS  Google Scholar 

  26. Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, Huber P, Muller B, Tamm M. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007;131(1):9–19.

    Article  CAS  Google Scholar 

  27. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, 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;302(10):1059–66.

    Article  CAS  Google Scholar 

  28. Schuetz P, Christ-Crain M, Zimmerli W, Mueller B. Guidance of antibiotic therapy with procalcitonin in lower respiratory tract infections: insights into the ProHOSP study. Virulence. 2010;1:88–92.

    Article  Google Scholar 

  29. Evans AT, Husain S, Durairaj L, Sadowski LS, Charles-Damte M, Wang Y. Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Lancet. 2002;359(9318):1648–54.

    Article  CAS  Google Scholar 

  30. Burkhardt O, Ewig S, Haagen U, Giersdorf S, Hartmann O, Wegscheider K, Hummers-Pradier E, Welte T. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J. 2010;36(3):601–7.

    Article  CAS  Google Scholar 

  31. Briel M, Christ-Crain M, Young J, Schuetz P, Huber P, Periat P, Bucher HC, Muller B. Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]. BMC Fam Pract. 2005;6:34.

    Article  Google Scholar 

  32. Briel M, Schuetz P, Mueller B, Young J, Schild U, Nusbaumer C, Periat P, Bucher HC, Christ-Crain M. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008;168(18):2000–2007; discussion 2007–2008.

    Article  Google Scholar 

  33. Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;9(9):CD007498.

    Google Scholar 

  34. Schuetz P, Briel M, Christ-Crain M, Stolz D, Bouadma L, Wolff M, Luyt CE, Chastre J, Tubach F, Kristoffersen KB, et al. Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis. Clin Infect Dis. 2012;55(5):651–62.

    Article  CAS  Google Scholar 

  35. 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 Respir Crit Care Med. 2008;177(5):498–505.

    Article  CAS  Google Scholar 

  36. Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375(9713):463–74.

    Article  CAS  Google Scholar 

  37. de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE, Loef BG, Dormans T, van Melsen GC, Kluiters YC, 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;16(7):819–27.

    Article  Google Scholar 

  38. Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, Marsch S, Azzola A, Rakic J, Mueller B, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J. 2009;34(6):1364–75.

    Article  CAS  Google Scholar 

  39. Woodhead M, Blasi F, Ewig S, Garau J, Huchon M, Leven M, Ortqvist A, Schaberg T, Torres A, Read R, et al. Guidelines for the management of adult lower respiratory tract infections. Clin Microbiol Infect. 2011;17(Suppl. 6):E1–E59.

    Article  Google Scholar 

  40. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.

    Article  CAS  Google Scholar 

  41. Schuetz P, Christ-Crain M, Zimmerli W, Mueller B. Repeated measurements of endothelin-1 precursor peptides predict the outcome in community-acquired pneumonia. Intensive Care Med. 2011;37(6):970–80.

    Article  CAS  Google Scholar 

  42. Christ-Crain M, Muller B. Procalcitonin in bacterial infections—hype, hope, more or less? Swiss Med Wkly. 2005;135(31–32):451–60.

    CAS  PubMed  Google Scholar 

  43. Schuetz P, Balk R, Briel M, Kutz A, Christ-Crain M, Stolz D, Bouadma L, Wolff M, Kristoffersen KB, Wei L, et al. Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective. Clin Chem Lab Med. 2015;53(4):583–92.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing Switzerland

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Schuetz, P., Sager, R., Wirz, Y., Mueller, B. (2018). Procalcitonin and Other Host-Response-Based Biomarkers for Evaluation of Infection and Guidance of Antimicrobial Treatment. In: Tang, YW., Stratton, C. (eds) Advanced Techniques in Diagnostic Microbiology. Springer, Cham. https://doi.org/10.1007/978-3-319-33900-9_7

Download citation

Publish with us

Policies and ethics