REVIEW URRENT C OPINION
Use of procalcitonin for the prediction and treatment of acute bacterial infection in children Richard Pierce a, Michael T. Bigham b, and John S. Giuliano Jr c
Purpose of review Procalcitonin (PCT) is increasingly utilized to determine the presence of infection or to guide antibiotic therapy. This review will highlight the diagnostic and prognostic utility of serum PCT in children. Recent findings Recent studies endorse the use of serum PCT to detect invasive infection, to differentiate sepsis from noninfectious systemic inflammatory response syndrome, and to guide antibiotic therapy. Typical values for maximal sensitivity and specificity are less than 0.5 ng/ml for noninfectious inflammation and greater than 2.0 ng/ml for bacterial sepsis. PCT appears to be a reliable indicator of infection. PCT has performed better than C-reactive protein in some settings, though pediatric comparative data are lacking. PCT may aid in diagnosing infection in challenging patient populations such as those with sickle cell disease, congenital heart defects, neutropenia, and indwelling central venous catheters. Antibiotic therapy tailored to serial PCT measurements may shorten the antibiotic exposure without increasing treatment failure. Summary PCT is a reliable serum marker for determining the presence or absence of invasive bacterial infection and response to antibiotic therapy. Tailoring antibiotics to PCT levels may reduce the duration of therapy without increasing treatment failure, but more research is needed in children. Keywords antibiotics, biomarkers, pediatrics, sepsis
INTRODUCTION
PHYSIOLOGY OF PROCALCITONIN
Procalcitonin (PCT) is an amino acid peptide initially investigated in 1961 as a tumor marker for medullary thyroid carcinoma [1]. During homeostasis, PCT is produced exclusively by the neuroendocrine cells and circulates at very low levels. Increases in serum PCT were first noted in adults with Staphylococcal toxic shock syndrome in the early 1980s [1]. Since then, PCT has been extensively studied in adults and children as a marker for bacterial infection in a myriad of clinical scenarios ranging from appendicitis to zoonoses. The most promising PCT research has focused on four main areas: confirming serious bacterial illness (SBI) in previously healthy individuals; ruling out SBI in susceptible populations such as neonates, immunocompromised patients, and those with chronic conditions; differentiating between sepsis and systemic inflammatory response syndrome (SIRS); and monitoring response to and tailoring antibiotic therapy.
During homeostasis, the CALC-I gene is expressed primarily in the C-cells of the thyroid, producing preprocalcitonin. This is subsequently cleaved to produce PCT and finally calcitonin. Very little PCT (0.5 ng/ml positive pneumonia 34 weeks with concern for sepsis
Cohen 2012 [41]
Stocker 2010 [42]
Antibiotics were discontinued after two consecutive PCT below predefined GA values
Two children’s hospitals 337 children with lower respiratory tract infection Baer 2013 [40 ] &&
319 hospitalized children with simple mild to moderate pneumonia Esposito 2011 [39]
LR, negative likelihood ratio; þLR, positive likelihood ratio; CAP, community acquired pneumonia; GA, gestational age; PCT, procalcitonin; Sens, sensitivity; Spec, specificity. The 95% confidence interval is given in parenthesis.
Not validated in severe or complicated pneumonia Significantly reduced antibiotic exposure with no adverse events Treatment with antibiotics until PCT level was < 0.25 ng/ml
Clinical outcome was similar and favorable in both groups.
Comments Results PCT cutoff values # Patients Authors & date
Table 2. Procalcitonin-guided antibiotic therapy
Procalcitonin use in children with infection Pierce et al.
in the adult ICU setting found significant decreases in antibiotic exposure and no change in hospital or 28-day mortality with PCT-guided therapy compared with standard therapy [37]. Finally, a large, multicenter RCT entitled ‘Stop Antibiotics on guidance of Procalcitonin Study’ (SAPS) is currently enrolling and should clarify PCT-guided therapy in adults [38]. Fewer pediatric trials using PCT-guided antibiotic therapy exist (Table 2). Hospitalized children with pneumonia were treated until PCT levels were less than 0.25 ng/ml and had significantly less antibiotic exposure with no increase in morbidity or mortality [39]. A similar study targeted PCT levels less than 0.25 ng/ml or 90% drop from the initial PCT value and found significantly less antibiotic exposure with no recurrence of infection [40 ]. A retrospective study in children found that PCT was a better marker of antibiotic response to pneumococcal pneumonia than CRP or WBC [41]. The only study investigating PCT-guided therapy in critically ill neonates with early-onset sepsis found that PCTguided therapy to age-adjusted PCT values shortened the antibiotic course by 22.4 h, with no changes in unfavorable clinical outcomes [42]. They caution, however, that their sample size of 121 newborns is insufficient to exclude rare adverse events. &&
CONCLUSION PCT has demonstrated diagnostic and therapeutic utility in a variety of clinical situations. It is a reliable serum marker for the presence or absence of invasive bacterial infection and response to antibiotic therapy. Typical values for maximal sensitivity and specificity in the context of ‘ruling out’ or ‘ruling in’ SBI in children and neonates are less than 0.5 ng/ml and greater than 2.0 ng/ml, respectively. Similar values are appropriate for children with febrile neutropenia or sickle cell disease, or patients with CVCs. Tailoring antibiotics to PCT less than 0.25 ng/ml or below age appropriate values may reduce the duration of therapy without increasing treatment failure, but more research is required in children. There is modest evidence that PCT is superior to CRP. With many studies supporting CRP as well as PCT, differences in cost, availability, and assay sensitivity may influence the clinical use. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
1040-8703 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-pediatrics.com
297
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Emergency and critical care medicine
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Becker KL, Nylen ES, White JC, et al. 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: 1512–1525. 2. Becker KL, Snider R, Nylen ES. Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. Br J Pharmacol 2010; 159:253–264. 3. Riedel S. Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis. Diagn Microbiol Infect Dis 2012; 73:221–227. 4. Liappis AP, Gibbs KW, Nylen ES, et al. Exogenous procalcitonin evokes a proinflammatory cytokine response. Inflamm Res 2011; 60:203–207. 5. 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; 30:2091– 2095. 6. Wiedermann FJ, Kaneider N, Egger P, et al. Migration of human monocytes in response to procalcitonin. Crit Care Med 2002; 30:1112–1117. 7. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 2008; 36:941–952. 8. Auriti C, Fiscarelli E, Ronchetti MP, et al. Procalcitonin in detecting neonatal & nosocomial sepsis. Arch Dis Child Fetal Neonatal Ed 2012; 97:F368–F370. This prospective multicenter observational study of almost 800 neonates makes it one of the largest studies on PCT in neonates. It stratifies the results by PCT level and birth weight. 9. Vouloumanou EK, Plessa E, Karageorgopoulos DE, et al. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and metaanalysis. Intensive Care Med 2011; 37:747–762. 10. Gomez B, Bressan S, Mintegi S, et al. Diagnostic value of procalcitonin in well appearing young febrile infants. Pediatrics 2012; 130:815–822. 11. Van den Bruel A, Thompson MJ, Haj-Hassan T, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ 2011; 342:d3082. 12. Yo CH, Hsieh PS, Lee SH, 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; 60:591–600. This recent systematic review and meta-analysis directly compares the diagnostic ability of PCT, CRP, and WBC. They conclude that PCT is superior to CRP and WBC in most clinical scenarios. 13. Bressan S, Gomez B, Mintegi S, et al. Diagnostic performance of the labscore in predicting severe and invasive bacterial infections in well appearing young febrile infants. Pediatr Infect Dis J 2012; 31:1239–1244. 14. Leroy S, Fernandez-Lopez A, Nikfar R, et al. Association of procalcitonin with & acute pyelonephritis and renal scars in pediatric UTI. Pediatrics 2013; 131:870–879. This is the largest systematic review and meta-analysis involving 18 studies comparing the prognostic ability of CRP and PCT in determining pyelonephritis and subsequent renal scarring. They determine PCT is superior in this setting. 15. Phillips RS, Wade R, Lehrnbecher T, et al. Systematic review and metaanalysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer. BMC Med 2012; 10:6. 16. 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:e182–e188. 17. Mathew B, Roy DD, Kumar TV. The use of procalcitonin as a marker of sepsis in children. J Clin Diagn Res 2013; 7:305–307. 18. Van Rossum AM, Wulkan RW, Oudesluys-Murphy AM. Procalcitonin as an early marker of infection in neonates and children. Lancet Infect Dis 2004; 4:620–630. 19. Nahum E, Schiller O, Livni G, et al. Procalcitonin level as an aid for the & diagnosis of bacterial infections following pediatric cardiac surgery. J Crit Care 2012; 27:220.e11–220.e16. This is a nested case–control study comparing PCT and CRP to determine the presence of infection in febrile children undergoing cardiac surgery. In this setting, PCT appears to be superior to CRP. 20. Garcia IJ, Gargallo MB, Torne EE, et al. Procalcitonin: a useful biomarker to discriminate infection after cardiopulmonary bypass in children. Pediatr Crit Care Med 2012; 13:441–445.
298
www.co-pediatrics.com
21. Rungatscher A, Merlini A, De Rita F, et al. Diagnosis of infection in paediatric veno-arterial cardiac extracorporeal membrane oxygenation: role of procalcitonin and C-reactive protein. Eur J Cardiothorac Surg 2013; 43:1043–1049. 22. Leroy S, Romanello C, Galetto-Lacour A, et al. Procalcitonin is a predictor for high-grade vesicoureteral reflux in children: meta-analysis of individual patient data. J Pediatr 2011; 159:644.e4–651.e4. 23. Unal S, Arslankoylu A, Kuyucu N, et al. Procalcitonin is more useful than C-reactive protein in fever in patients with sickle cell disease. J Pediatr Hematol Oncol 2012; 34:85–89. 24. Bulloch AJK, Henry B, Shah M, et al. Procalcitonin as a marker of bacteremia in children with fever and a central venous catheter presenting to the emergency department. Pediatr Emerg Care 2012; 28:1017–1021. 25. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med 2013; 41:580–637. 26. Uzzan B, Cohen R, Nicolas P, et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med 2006; 34:1996–2003. 27. Tang BMP, 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; 7:210–217. 28. 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; 13:426–435. 29. Han YY, Doughty LA, Kofos D, et al. Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Pediatr Crit Care Med 2003; 4:21–25. 30. Arkader R, Troster EJ, Lopes MR, et al. Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child 2006; 91:117–120. 31. Rey C, Los Arcos M, Concha A, et al. Procalcitonin and C-reactive protein as markers of systemic inflammatory response syndrome severity in critically ill children. Intensive Care Med 2007; 33:477–484. 32. Rey C, Garcia-Hernandez I, Concha A, et al. Pro-adrenomedullin, pro&& endothelin 1, procalcitonin, C-reactive protein and mortality risk in critically ill children. Crit Care 2013; 17:R240. [Epub ahead of print] This is a prospective, two-center observational study comparing the prognostic ability of PCT with other recently identified biomarkers. The authors conclude that PCT greater than 2 ng/ml predicts increased mortality. 33. Schuetz P, Muller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; 9:CD007498. 34. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitoninguided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 2004; 363:600–607. 35. Oliveira CF, Botoni FA, Oliveira CR, et al. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med 2013; 41:2336–2343. 36. 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; 39:1792–1799. 37. 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:R291. 38. Assink-de Jong E, de Lange DW, van Oers JA, et al. Stop Antibiotics on guidance of Procalcitonin Study (SAPS): a randomized prospective multicenter investigator-initiated trial to analyse whether daily measurements of procalcitonin versus a standard-of-care approach can safely shorten antibiotic duration in intensive care unit patients – calculated sample size: 1816 patients. BMC Infect Dis 2013; 13. 39. Esposito S, Tagliabue C, Picciolli I, et al. Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia. Respir Med 2011; 105: 1939–1945. 40. 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: e68419. A well-designed prospective randomized clinical trial of PCT-guided therapy in lower respiratory tract infections in children and adolescents. The authors found that PCT guidance reduced the antibiotic exposure without any adverse events. 41. Cohen JF, Leis A, Lecarpentier T, et al. Procalcitonin predicts response to beta-lactam treatment in hospitalized children with community-acquired pneumonia. PLoS One 2012; 7:e36927. 42. Stocker M, Fontana M, El Helou S, et al. Use of procalcitonin-guided decision-making to shorten antibiotic therapy in suspected neonatal early-onset sepsis: prospective randomized intervention trial. Neonatology 2010; 97:165–174.
Volume 26 Number 3 June 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Use of procalcitonin for the prediction and treatment of acute bacterial infection in children Richard Pierce a, Michael T. Bigham b, and John S. Giuliano Jr c
Purpose of review Procalcitonin (PCT) is increasingly utilized to determine the presence of infection or to guide antibiotic therapy. This review will highlight the diagnostic and prognostic utility of serum PCT in children. Recent findings Recent studies endorse the use of serum PCT to detect invasive infection, to differentiate sepsis from noninfectious systemic inflammatory response syndrome, and to guide antibiotic therapy. Typical values for maximal sensitivity and specificity are less than 0.5 ng/ml for noninfectious inflammation and greater than 2.0 ng/ml for bacterial sepsis. PCT appears to be a reliable indicator of infection. PCT has performed better than C-reactive protein in some settings, though pediatric comparative data are lacking. PCT may aid in diagnosing infection in challenging patient populations such as those with sickle cell disease, congenital heart defects, neutropenia, and indwelling central venous catheters. Antibiotic therapy tailored to serial PCT measurements may shorten the antibiotic exposure without increasing treatment failure. Summary PCT is a reliable serum marker for determining the presence or absence of invasive bacterial infection and response to antibiotic therapy. Tailoring antibiotics to PCT levels may reduce the duration of therapy without increasing treatment failure, but more research is needed in children. Keywords antibiotics, biomarkers, pediatrics, sepsis
INTRODUCTION
PHYSIOLOGY OF PROCALCITONIN
Procalcitonin (PCT) is an amino acid peptide initially investigated in 1961 as a tumor marker for medullary thyroid carcinoma [1]. During homeostasis, PCT is produced exclusively by the neuroendocrine cells and circulates at very low levels. Increases in serum PCT were first noted in adults with Staphylococcal toxic shock syndrome in the early 1980s [1]. Since then, PCT has been extensively studied in adults and children as a marker for bacterial infection in a myriad of clinical scenarios ranging from appendicitis to zoonoses. The most promising PCT research has focused on four main areas: confirming serious bacterial illness (SBI) in previously healthy individuals; ruling out SBI in susceptible populations such as neonates, immunocompromised patients, and those with chronic conditions; differentiating between sepsis and systemic inflammatory response syndrome (SIRS); and monitoring response to and tailoring antibiotic therapy.
During homeostasis, the CALC-I gene is expressed primarily in the C-cells of the thyroid, producing preprocalcitonin. This is subsequently cleaved to produce PCT and finally calcitonin. Very little PCT (0.5 ng/ml positive pneumonia 34 weeks with concern for sepsis
Cohen 2012 [41]
Stocker 2010 [42]
Antibiotics were discontinued after two consecutive PCT below predefined GA values
Two children’s hospitals 337 children with lower respiratory tract infection Baer 2013 [40 ] &&
319 hospitalized children with simple mild to moderate pneumonia Esposito 2011 [39]
LR, negative likelihood ratio; þLR, positive likelihood ratio; CAP, community acquired pneumonia; GA, gestational age; PCT, procalcitonin; Sens, sensitivity; Spec, specificity. The 95% confidence interval is given in parenthesis.
Not validated in severe or complicated pneumonia Significantly reduced antibiotic exposure with no adverse events Treatment with antibiotics until PCT level was < 0.25 ng/ml
Clinical outcome was similar and favorable in both groups.
Comments Results PCT cutoff values # Patients Authors & date
Table 2. Procalcitonin-guided antibiotic therapy
Procalcitonin use in children with infection Pierce et al.
in the adult ICU setting found significant decreases in antibiotic exposure and no change in hospital or 28-day mortality with PCT-guided therapy compared with standard therapy [37]. Finally, a large, multicenter RCT entitled ‘Stop Antibiotics on guidance of Procalcitonin Study’ (SAPS) is currently enrolling and should clarify PCT-guided therapy in adults [38]. Fewer pediatric trials using PCT-guided antibiotic therapy exist (Table 2). Hospitalized children with pneumonia were treated until PCT levels were less than 0.25 ng/ml and had significantly less antibiotic exposure with no increase in morbidity or mortality [39]. A similar study targeted PCT levels less than 0.25 ng/ml or 90% drop from the initial PCT value and found significantly less antibiotic exposure with no recurrence of infection [40 ]. A retrospective study in children found that PCT was a better marker of antibiotic response to pneumococcal pneumonia than CRP or WBC [41]. The only study investigating PCT-guided therapy in critically ill neonates with early-onset sepsis found that PCTguided therapy to age-adjusted PCT values shortened the antibiotic course by 22.4 h, with no changes in unfavorable clinical outcomes [42]. They caution, however, that their sample size of 121 newborns is insufficient to exclude rare adverse events. &&
CONCLUSION PCT has demonstrated diagnostic and therapeutic utility in a variety of clinical situations. It is a reliable serum marker for the presence or absence of invasive bacterial infection and response to antibiotic therapy. Typical values for maximal sensitivity and specificity in the context of ‘ruling out’ or ‘ruling in’ SBI in children and neonates are less than 0.5 ng/ml and greater than 2.0 ng/ml, respectively. Similar values are appropriate for children with febrile neutropenia or sickle cell disease, or patients with CVCs. Tailoring antibiotics to PCT less than 0.25 ng/ml or below age appropriate values may reduce the duration of therapy without increasing treatment failure, but more research is required in children. There is modest evidence that PCT is superior to CRP. With many studies supporting CRP as well as PCT, differences in cost, availability, and assay sensitivity may influence the clinical use. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
1040-8703 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-pediatrics.com
297
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Emergency and critical care medicine
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Becker KL, Nylen ES, White JC, et al. 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: 1512–1525. 2. Becker KL, Snider R, Nylen ES. Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. Br J Pharmacol 2010; 159:253–264. 3. Riedel S. Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis. Diagn Microbiol Infect Dis 2012; 73:221–227. 4. Liappis AP, Gibbs KW, Nylen ES, et al. Exogenous procalcitonin evokes a proinflammatory cytokine response. Inflamm Res 2011; 60:203–207. 5. 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; 30:2091– 2095. 6. Wiedermann FJ, Kaneider N, Egger P, et al. Migration of human monocytes in response to procalcitonin. Crit Care Med 2002; 30:1112–1117. 7. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 2008; 36:941–952. 8. Auriti C, Fiscarelli E, Ronchetti MP, et al. Procalcitonin in detecting neonatal & nosocomial sepsis. Arch Dis Child Fetal Neonatal Ed 2012; 97:F368–F370. This prospective multicenter observational study of almost 800 neonates makes it one of the largest studies on PCT in neonates. It stratifies the results by PCT level and birth weight. 9. Vouloumanou EK, Plessa E, Karageorgopoulos DE, et al. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and metaanalysis. Intensive Care Med 2011; 37:747–762. 10. Gomez B, Bressan S, Mintegi S, et al. Diagnostic value of procalcitonin in well appearing young febrile infants. Pediatrics 2012; 130:815–822. 11. Van den Bruel A, Thompson MJ, Haj-Hassan T, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ 2011; 342:d3082. 12. Yo CH, Hsieh PS, Lee SH, 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; 60:591–600. This recent systematic review and meta-analysis directly compares the diagnostic ability of PCT, CRP, and WBC. They conclude that PCT is superior to CRP and WBC in most clinical scenarios. 13. Bressan S, Gomez B, Mintegi S, et al. Diagnostic performance of the labscore in predicting severe and invasive bacterial infections in well appearing young febrile infants. Pediatr Infect Dis J 2012; 31:1239–1244. 14. Leroy S, Fernandez-Lopez A, Nikfar R, et al. Association of procalcitonin with & acute pyelonephritis and renal scars in pediatric UTI. Pediatrics 2013; 131:870–879. This is the largest systematic review and meta-analysis involving 18 studies comparing the prognostic ability of CRP and PCT in determining pyelonephritis and subsequent renal scarring. They determine PCT is superior in this setting. 15. Phillips RS, Wade R, Lehrnbecher T, et al. Systematic review and metaanalysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer. BMC Med 2012; 10:6. 16. 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:e182–e188. 17. Mathew B, Roy DD, Kumar TV. The use of procalcitonin as a marker of sepsis in children. J Clin Diagn Res 2013; 7:305–307. 18. Van Rossum AM, Wulkan RW, Oudesluys-Murphy AM. Procalcitonin as an early marker of infection in neonates and children. Lancet Infect Dis 2004; 4:620–630. 19. Nahum E, Schiller O, Livni G, et al. Procalcitonin level as an aid for the & diagnosis of bacterial infections following pediatric cardiac surgery. J Crit Care 2012; 27:220.e11–220.e16. This is a nested case–control study comparing PCT and CRP to determine the presence of infection in febrile children undergoing cardiac surgery. In this setting, PCT appears to be superior to CRP. 20. Garcia IJ, Gargallo MB, Torne EE, et al. Procalcitonin: a useful biomarker to discriminate infection after cardiopulmonary bypass in children. Pediatr Crit Care Med 2012; 13:441–445.
298
www.co-pediatrics.com
21. Rungatscher A, Merlini A, De Rita F, et al. Diagnosis of infection in paediatric veno-arterial cardiac extracorporeal membrane oxygenation: role of procalcitonin and C-reactive protein. Eur J Cardiothorac Surg 2013; 43:1043–1049. 22. Leroy S, Romanello C, Galetto-Lacour A, et al. Procalcitonin is a predictor for high-grade vesicoureteral reflux in children: meta-analysis of individual patient data. J Pediatr 2011; 159:644.e4–651.e4. 23. Unal S, Arslankoylu A, Kuyucu N, et al. Procalcitonin is more useful than C-reactive protein in fever in patients with sickle cell disease. J Pediatr Hematol Oncol 2012; 34:85–89. 24. Bulloch AJK, Henry B, Shah M, et al. Procalcitonin as a marker of bacteremia in children with fever and a central venous catheter presenting to the emergency department. Pediatr Emerg Care 2012; 28:1017–1021. 25. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med 2013; 41:580–637. 26. Uzzan B, Cohen R, Nicolas P, et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med 2006; 34:1996–2003. 27. Tang BMP, 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; 7:210–217. 28. 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; 13:426–435. 29. Han YY, Doughty LA, Kofos D, et al. Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Pediatr Crit Care Med 2003; 4:21–25. 30. Arkader R, Troster EJ, Lopes MR, et al. Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child 2006; 91:117–120. 31. Rey C, Los Arcos M, Concha A, et al. Procalcitonin and C-reactive protein as markers of systemic inflammatory response syndrome severity in critically ill children. Intensive Care Med 2007; 33:477–484. 32. Rey C, Garcia-Hernandez I, Concha A, et al. Pro-adrenomedullin, pro&& endothelin 1, procalcitonin, C-reactive protein and mortality risk in critically ill children. Crit Care 2013; 17:R240. [Epub ahead of print] This is a prospective, two-center observational study comparing the prognostic ability of PCT with other recently identified biomarkers. The authors conclude that PCT greater than 2 ng/ml predicts increased mortality. 33. Schuetz P, Muller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; 9:CD007498. 34. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitoninguided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 2004; 363:600–607. 35. Oliveira CF, Botoni FA, Oliveira CR, et al. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med 2013; 41:2336–2343. 36. 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; 39:1792–1799. 37. 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:R291. 38. Assink-de Jong E, de Lange DW, van Oers JA, et al. Stop Antibiotics on guidance of Procalcitonin Study (SAPS): a randomized prospective multicenter investigator-initiated trial to analyse whether daily measurements of procalcitonin versus a standard-of-care approach can safely shorten antibiotic duration in intensive care unit patients – calculated sample size: 1816 patients. BMC Infect Dis 2013; 13. 39. Esposito S, Tagliabue C, Picciolli I, et al. Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia. Respir Med 2011; 105: 1939–1945. 40. 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: e68419. A well-designed prospective randomized clinical trial of PCT-guided therapy in lower respiratory tract infections in children and adolescents. The authors found that PCT guidance reduced the antibiotic exposure without any adverse events. 41. Cohen JF, Leis A, Lecarpentier T, et al. Procalcitonin predicts response to beta-lactam treatment in hospitalized children with community-acquired pneumonia. PLoS One 2012; 7:e36927. 42. Stocker M, Fontana M, El Helou S, et al. Use of procalcitonin-guided decision-making to shorten antibiotic therapy in suspected neonatal early-onset sepsis: prospective randomized intervention trial. Neonatology 2010; 97:165–174.
Volume 26 Number 3 June 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
