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J Pediatr Intensive Care 2016; 05(04): 162-171
DOI: 10.1055/s-0036-1583279
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Procalcitonin: Is This the Promised Biomarker for Critically Ill Patients?

Patricia S. Fontela
1   Department of Pediatrics, McGill University, Montreal, Quebec, Canada
2   Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
,
Jacques Lacroix
3   Department of Pediatrics, Université de Montréal, Montreal, Quebec, Canada
› Author Affiliations
Further Information

Publication History

28 August 2015

19 November 2015

Publication Date:
09 May 2016 (online)

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Abstract

Objective Procalcitonin (PCT) has been increasingly used in the critical care setting to determine the presence of bacterial infection and also to guide antibiotic therapy. We reviewed PCT's physiologic role, as well as its clinical utility for the management of pediatric critically ill patients.

Findings PCT is a precursor of the hormone calcitonin. Its production is induced by inflammatory conditions, especially bacterial infections. Literature shows that PCT is a moderately reliable diagnostic test for severe bacterial infection in children. Synthesis of available adult studies suggests that the use of PCT-based algorithms to support medical decision making reduces antibiotic exposure without compromising safety in critically ill patients. However, no study has addressed the usefulness and safety of PCT to guide antibiotic therapy in severely ill children. In pediatric patients with acute lower respiratory tract infections, the use of PCT-based algorithms also led to a safe decrease in antibiotic treatment duration.

Conclusion PCT has demonstrated clinical utility in the pediatric critical care setting when used for the diagnosis of bacterial infections and to guide antibiotic use in children with acute lower respiratory tract infections. However, more research is needed in critically ill children to determine the utility of PCT-driven antibiotic therapy in this population.

Keywords

procalcitonin - infection - children - critical care - antibiotics - medical decision making
 

  • References

  • 1 Audry-Degardin E, Dubos F, Leteurtre S, Beaucaire G, Leclerc F. Evaluation de la prescription antibiotique dans un service de réanimation pédiatrique [in French]. Arch Pediatr 2007; 14 (2) 157-163
    CrossrefPubMedGoogle Scholar
  • 2 Blinova E, Lau E, Bitnun A , et al. Point prevalence survey of antimicrobial utilization in the cardiac and pediatric critical care unit. Pediatr Crit Care Med 2013; 14 (6) e280-e288
    CrossrefPubMedGoogle Scholar
  • 3 Ceyhan M, Yildirim I, Ecevit C , et al. Inappropriate antimicrobial use in Turkish pediatric hospitals: a multicenter point prevalence survey. Int J Infect Dis 2010; 14 (1) e55-e61
    PubMedGoogle Scholar
  • 4 Ciofi Degli Atti ML, Raponi M, Tozzi AE, Ciliento G, Ceradini J, Langiano T. Point prevalence study of antibiotic use in a paediatric hospital in Italy. Euro Surveill 2008; 13 (41) 12-15
    PubMedGoogle Scholar
  • 5 Ding H, Yang Y, Chen Y, Wang Y, Fan S, Shen X. Antimicrobial usage in paediatric intensive care units in China. Acta Paediatr 2008; 97 (1) 100-104
    PubMedGoogle Scholar
  • 6 Ding H, Yang Y, Lu Q , et al. Five-year surveillance of antimicrobial use in Chinese pediatric intensive care units. J Trop Pediatr 2008; 54 (4) 238-242
    CrossrefPubMedGoogle Scholar
  • 7 Fischer JE, Ramser M, Fanconi S. Use of antibiotics in pediatric intensive care and potential savings. Intensive Care Med 2000; 26 (7) 959-966
    CrossrefPubMedGoogle Scholar
  • 8 Schneider HG, Lam QT. Procalcitonin for the clinical laboratory: a review. Pathology 2007; 39 (4) 383-390
    CrossrefPubMedGoogle Scholar
  • 9 Becker KL, Nylén ES, White JC, Müller B, Snider Jr RH. Clinical review 167: procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004; 89 (4) 1512-1525
    CrossrefPubMedGoogle Scholar
  • 10 Matwiyoff GN, Prahl JD, Miller RJ , et al. Immune regulation of procalcitonin: a biomarker and mediator of infection. Inflamm Res 2012; 61 (5) 401-409
    CrossrefPubMedGoogle Scholar
  • 11 Müller B, White JC, Nylén ES, Snider RH, Becker KL, Habener JF. Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 2001; 86 (1) 396-404
    CrossrefPubMedGoogle Scholar
  • 12 Dandona P, Nix D, Wilson MF , et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab 1994; 79 (6) 1605-1608
    CrossrefPubMedGoogle Scholar
  • 13 Maruna P, Nedelníková K, Gürlich R. Physiology and genetics of procalcitonin. Physiol Res 2000; 49 (Suppl. 01) S57-S61
    PubMedGoogle Scholar
  • 14 Bihan H, Becker KL, Snider RH , et al. Calcitonin precursor levels in human medullary thyroid carcinoma. Thyroid 2003; 13 (8) 819-822
    CrossrefPubMedGoogle Scholar
  • 15 Reinhart K, Meisner M. Biomarkers in the critically ill patient: procalcitonin. Crit Care Clin 2011; 27 (2) 253-263
    CrossrefPubMedGoogle Scholar
  • 16 Russwurm S, Wiederhold M, Oberhoffer M, Stonans I, Zipfel PF, Reinhart K. Molecular aspects and natural source of procalcitonin. Clin Chem Lab Med 1999; 37 (8) 789-797
    PubMedGoogle Scholar
  • 17 Morgenthaler NG, Struck J, Chancerelle Y , et al. Production of procalcitonin (PCT) in non-thyroidal tissue after LPS injection. Horm Metab Res 2003; 35 (5) 290-295
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Domenech VS, Nylen ES, White JC , et al. Calcitonin gene-related peptide expression in sepsis: postulation of microbial infection-specific response elements within the calcitonin I gene promoter. J Investig Med 2001; 49 (6) 514-521
    CrossrefPubMedGoogle Scholar
  • 19 Picariello C, Lazzeri C, Valente S, Chiostri M, Attanà P, Gensini GF. Kinetics of procalcitonin in cardiogenic shock and in septic shock. Preliminary data. Acute Card Care 2010; 12 (3) 96-101
    CrossrefPubMedGoogle Scholar
  • 20 Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 2008; 36 (3) 941-952
    CrossrefPubMedGoogle Scholar
  • 21 Whang KT, Vath SD, Becker KL , et al. Procalcitonin and proinflammatory cytokine interactions in sepsis. Shock 2000; 14 (1) 73-78
    CrossrefPubMedGoogle Scholar
  • 22 Nijsten MW, Olinga P, The TH , et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med 2000; 28 (2) 458-461
    CrossrefPubMedGoogle Scholar
  • 23 Liappis AP, Gibbs KW, Nylen ES , et al. Exogenous procalcitonin evokes a pro-inflammatory cytokine response. Inflamm Res 2011; 60 (2) 203-207
    CrossrefPubMedGoogle Scholar
  • 24 Wei JX, Verity A, Garle M, Mahajan R, Wilson V. Examination of the effect of procalcitonin on human leucocytes and the porcine isolated coronary artery. Br J Anaesth 2008; 100 (5) 612-621
    CrossrefPubMedGoogle Scholar
  • 25 Wiedermann FJ, Kaneider N, Egger P , et al. Migration of human monocytes in response to procalcitonin. Crit Care Med 2002; 30 (5) 1112-1117
    CrossrefPubMedGoogle Scholar
  • 26 Steinwald PM, Whang KT, Becker KL, Snider RH, Nylen ES, White JC. Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis. Crit Care 1999; 3 (1) 11-16
    CrossrefPubMedGoogle Scholar
  • 27 Hoffmann G, Czechowski M, Schloesser M, Schobersberger W. Procalcitonin amplifies inducible nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle cells. Crit Care Med 2002; 30 (9) 2091-2095
    CrossrefPubMedGoogle Scholar
  • 28 Nylen ES, Whang KT, Snider Jr RH, Steinwald PM, White JC, Becker KL. Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis. Crit Care Med 1998; 26 (6) 1001-1006
    CrossrefPubMedGoogle Scholar
  • 29 Wagner KE, Martinez JM, Vath SD , et al. Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs. Crit Care Med 2002; 30 (10) 2313-2321
    CrossrefPubMedGoogle Scholar
  • 30 Martinez JM, Wagner KE, Snider RH , et al. Late immunoneutralization of procalcitonin arrests the progression of lethal porcine sepsis. Surg Infect (Larchmt) 2001; 2 (3) 193-202 , discussion 202–203
    CrossrefPubMedGoogle Scholar
  • 31 Serezani CH, Ballinger MN, Aronoff DM, Peters-Golden M. Cyclic AMP: master regulator of innate immune cell function. Am J Respir Cell Mol Biol 2008; 39 (2) 127-132
    CrossrefPubMedGoogle Scholar
  • 32 Brunkhorst FM, Heinz U, Forycki ZF. Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med 1998; 24 (8) 888-889
    CrossrefPubMedGoogle Scholar
  • 33 Castelli GP, Pognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L. Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care 2004; 8 (4) R234-R242
    CrossrefPubMedGoogle Scholar
  • 34 Miki T, Iba T. Kinetics of circulating damage-associated molecular patterns in sepsis. J Immunol Res 2015; 2015: 424575
    PubMedGoogle Scholar
  • 35 Reynolds SC, Shorr AF, Muscedere J, Jiang X, Heyland DK. Longitudinal changes in procalcitonin in a heterogeneous group of critically ill patients. Crit Care Med 2012; 40 (10) 2781-2787
    CrossrefPubMedGoogle Scholar
  • 36 Ugarte H, Silva E, Mercan D, De Mendonça A, Vincent JL. Procalcitonin used as a marker of infection in the intensive care unit. Crit Care Med 1999; 27 (3) 498-504
    CrossrefPubMedGoogle Scholar
  • 37 Charles PE, Tinel C, Barbar S , et al. Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome. Crit Care 2009; 13 (2) R38
    CrossrefPubMedGoogle Scholar
  • 38 Liu D, Su L, Han G, Yan P, Xie L. Prognostic value of procalcitonin in adult patients with sepsis: a systematic review and meta-analysis. PLoS ONE 2015; 10 (6) e0129450
    CrossrefPubMedGoogle Scholar
  • 39 Alkholi UM, Abd Al-Monem N, Abd El-Azim AA, Sultan MH. Serum procalcitonin in viral and bacterial meningitis. J Glob Infect Dis 2011; 3 (1) 14-18
    CrossrefPubMedGoogle Scholar
  • 40 Arkader R, Troster EJ, Lopes MR , et al. Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child 2006; 91 (2) 117-120
    PubMedGoogle Scholar
  • 41 Casado-Flores J, Blanco-Quirós A, Asensio J, Arranz E, Garrote JA, Nieto M. Serum procalcitonin in children with suspected sepsis: a comparison with C-reactive protein and neutrophil count. Pediatr Crit Care Med 2003; 4 (2) 190-195
    CrossrefPubMedGoogle Scholar
  • 42 Han YY, Doughty LA, Kofos D, Sasser H, Carcillo JA. Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Pediatr Crit Care Med 2003; 4 (1) 21-25
    CrossrefPubMedGoogle Scholar
  • 43 Secmeer G, Devrim I, Kara A , et al. Role of procalcitonin and CRP in differentiating a stable from a deteriorating clinical course in pediatric febrile neutropenia. J Pediatr Hematol Oncol 2007; 29 (2) 107-111
    CrossrefPubMedGoogle Scholar
  • 44 Van der Kaay DCM, De Kleijn ED, De Rijke YB, Hop WCJ, De Groot R, Hazelzet JA. Procalcitonin as a prognostic marker in meningococcal disease. Intensive Care Med 2002; 28 (11) 1606-1612
    CrossrefPubMedGoogle Scholar
  • 45 Garcia IJ, Gargallo MB, Torné EE , et al. Procalcitonin: a useful biomarker to discriminate infection after cardiopulmonary bypass in children. Pediatr Crit Care Med 2012; 13 (4) 441-445
    CrossrefPubMedGoogle Scholar
  • 46 Zurek J, Vavrina M. Procalcitonin biomarker kinetics to predict multiorgan dysfunction syndrome in children with sepsis and systemic inflammatory response syndrome. Iran J Pediatr 2015; 25 (1) e324
    PubMedGoogle Scholar
  • 47 Arkader R, Troster EJ, Abellan DM , et al. Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients. J Cardiothorac Vasc Anesth 2004; 18 (2) 160-165
    CrossrefPubMedGoogle Scholar
  • 48 Beghetti M, Rimensberger PC, Kalangos A, Habre W, Gervaix A. Kinetics of procalcitonin, interleukin 6 and C-reactive protein after cardiopulmonary-bypass in children. Cardiol Young 2003; 13 (2) 161-167
    CrossrefPubMedGoogle Scholar
  • 49 Hatherill M, Tibby SM, Sykes K, Turner C, Murdoch IA. Diagnostic markers of infection: comparison of procalcitonin with C reactive protein and leucocyte count. Arch Dis Child 1999; 81 (5) 417-421
    CrossrefPubMedGoogle Scholar
  • 50 Jones AE, Fiechtl JF, Brown MD, Ballew JJ, Kline JA. Procalcitonin test in the diagnosis of bacteremia: a meta-analysis. Ann Emerg Med 2007; 50 (1) 34-41
    CrossrefPubMedGoogle Scholar
  • 51 de Kruif MD, Lemaire LC, Giebelen IA , et al. The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med 2008; 34 (3) 518-522
    CrossrefPubMedGoogle Scholar
  • 52 Perren A, Cerutti B, Lepori M , et al. Influence of steroids on procalcitonin and C-reactive protein in patients with COPD and community-acquired pneumonia. Infection 2008; 36 (2) 163-166
    CrossrefPubMedGoogle Scholar
  • 53 Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007; 7 (3) 210-217
    CrossrefPubMedGoogle Scholar
  • 54 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) 426-435
    CrossrefPubMedGoogle Scholar
  • 55 Bell JM, Shields MD, Agus A , et al. Clinical and cost-effectiveness of procalcitonin test for prodromal meningococcal disease-a meta-analysis. PLoS ONE 2015; 10 (6) e0128993
    CrossrefPubMedGoogle Scholar
  • 56 England JT, Del Vecchio MT, Aronoff SC. Use of serum procalcitonin in evaluation of febrile infants: a meta-analysis of 2317 patients. J Emerg Med 2014; 47 (6) 682-688
    CrossrefPubMedGoogle Scholar
  • 57 Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004; 39 (2) 206-217
    CrossrefPubMedGoogle Scholar
  • 58 Yo C-H, Hsieh P-S, Lee S-H , et al. Comparison of the test characteristics of procalcitonin to C-reactive protein and leukocytosis for the detection of serious bacterial infections in children presenting with fever without source: a systematic review and meta-analysis. Ann Emerg Med 2012; 60 (5) 591-600
    CrossrefPubMedGoogle Scholar
  • 59 Lin SG, Hou TY, Huang DH , et al. Role of procalcitonin in the diagnosis of severe infection in pediatric patients with fever and neutropenia—a systemic review and meta-analysis. Pediatr Infect Dis J 2012; 31 (10) e182-e188
    PubMedGoogle Scholar
  • 60 Laham JL, Breheny PJ, Gardner BM, Bada H. Procalcitonin to predict bacterial coinfection in infants with acute bronchiolitis: a preliminary analysis. Pediatr Emerg Care 2014; 30 (1) 11-15
    CrossrefPubMedGoogle Scholar
  • 61 Hochreiter M, Köhler T, Schweiger AM , et al. Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care 2009; 13 (3) R83
    CrossrefPubMedGoogle Scholar
  • 62 Jensen JU, Hein L, Lundgren B , et al; Procalcitonin And Survival Study (PASS) Group. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 2011; 39 (9) 2048-2058
    CrossrefPubMedGoogle Scholar
  • 63 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
    CrossrefPubMedGoogle Scholar
  • 64 Schroeder S, Hochreiter M, Koehler T , 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; 394 (2) 221-226
    CrossrefPubMedGoogle Scholar
  • 65 Stolz D, Smyrnios N, Eggimann P , et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 2009; 34 (6) 1364-1375
    CrossrefPubMedGoogle Scholar
  • 66 Annane D, Maxime V, Faller JP , et al. Procalcitonin levels to guide antibiotic therapy in adults with non-microbiologically proven apparent severe sepsis: a randomised controlled trial. BMJ Open 2013; 3 (2) 3
    PubMedGoogle Scholar
  • 67 Shehabi Y, Sterba M, Garrett PM , et al; ProGUARD Study Investigators; ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. A randomized controlled trial. Am J Respir Crit Care Med 2014; 190 (10) 1102-1110
    CrossrefPubMedGoogle Scholar
  • 68 Bouadma L, Luyt C-E, Tubach F , et al; PRORATA trial group. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375 (9713) 463-474
    CrossrefPubMedGoogle Scholar
  • 69 Heyland DK, Johnson AP, Reynolds SC, Muscedere J. Procalcitonin for reduced antibiotic exposure in the critical care setting: a systematic review and an economic evaluation. Crit Care Med 2011; 39 (7) 1792-1799
    CrossrefPubMedGoogle Scholar
  • 70 Matthaiou DK, Ntani G, Kontogiorgi M, Poulakou G, Armaganidis A, Dimopoulos G. An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care Med 2012; 38 (6) 940-949
    CrossrefPubMedGoogle Scholar
  • 71 Prkno A, Wacker C, Brunkhorst FM, Schlattmann P. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock—a systematic review and meta-analysis. Crit Care 2013; 17 (6) R291
    CrossrefPubMedGoogle Scholar
  • 72 Schuetz P, Müller B, Christ-Crain M , et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; 9: CD007498
    PubMedGoogle Scholar
  • 73 Soni NJ, Samson DJ, Galaydick JL , et al. Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis. J Hosp Med 2013; 8 (9) 530-540
    CrossrefPubMedGoogle Scholar
  • 74 Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med 2010; 38 (11) 2229-2241
    CrossrefPubMedGoogle Scholar
  • 75 Esposito S, Tagliabue C, Picciolli I , et al. Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia. Respir Med 2011; 105 (12) 1939-1945
    CrossrefPubMedGoogle Scholar
  • 76 Baer G, Baumann P, Buettcher M , et al. Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infection in children and adolescents (ProPAED): a randomized controlled trial. PLoS ONE 2013; 8 (8) e68419
    CrossrefPubMedGoogle Scholar