Presepsin as a diagnostic marker of sepsis in children and adolescents: a short critical update
Keywords:
Children, Pediatric Emergency Department, Presepsin, Sepsis, Sepsis biomarkersAbstract
Background and aim: Sepsis is a potentially fatal condition which strikes 1.2 million children worldwide per year. New biomarkers have been proposed in the assessment of the risk of sepsis progression and in the identification of patients with the worst outcome. This review aims to assess the diagnostic value of presepsin, a promising new biomarker, in pediatric sepsis, with particular attention to its usefulness in emergency department.
Methods: We performed a literature search of the last 10 years to find presepsin related studies and reports concerning pediatric population aged from 0 months to 18 years. We mainly focused on randomized placebo-control studies, followed by case-control studies, observational (both retrospective or prospective), and finally systematic reviews and meta-analysis. The article selection process was carried out independently by three reviewers.
Results: A total of 60 records were identified in literature, 49 were excluded according to the exclusion criteria. The highest presepsin sensitivity value was 100%, with a high cut-off (800.5 pg/mL). The highest sensitivity-specificity ratio was 94% vs 100%, with a similar considered presepsin cut-off (855 ng/L). As regards the presepsin cut-offs reported in the various studies, several authors agree on a critical threshold of about 650 ng/L to guarantee a sensitivity> 90%. The analyzed studies show a wide variability for patients’ age and presepsin risk cut-offs.
Conclusions: Presepsin seems to be a new useful marker for early diagnosis of sepsis, even in a pediatric emergency setting. Being a new marker of sepsis, more studies are required to better understand its potential.
References
Velissaris D, Zareifopoulos N, Karamouzos V, et al. Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis. Cureus. Published online May 13, 2021. doi:10.7759/cureus.15019
Maddaloni C, De Rose DU, Santisi A, et al. The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review. IJMS. 2021;22(22):12154. doi:10.3390/ijms222212154
Piccioni A, Santoro MC, de Cunzo T, et al. Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review. Medicina. 2021;57(8):770. doi:10.3390/medicina57080770
Godnic M, Stubjar D, Skvarc M, Jukic T. Diagnostic and prognostic value of sCD14-ST—presepsin for patients admitted to hospital intensive care unit (ICU). Wien Klin Wochenschr. 2015;127(13-14):521-527. doi:10.1007/s00508-015-0719-5
Pizzolato E, Ulla M, Galluzzo C, et al. Role of presepsin for the evaluation of sepsis in the emergency department. Clinical Chemistry and Laboratory Medicine (CCLM). 2014;0(0). doi:10.1515/cclm-2014-0199
Poggi C, Bianconi T, Gozzini E, Generoso M, Dani C. Presepsin for the Detection of Late-Onset Sepsis in Preterm Newborns. Pediatrics. 2015;135(1):68-75. doi:10.1542/peds.2014-1755
Parri N, Trippella G, Lisi C, De Martino M, Galli L, Chiappini E. Accuracy of presepsin in neonatal sepsis: systematic review and meta-analysis. Expert Review of Anti-infective Therapy. 2019;17(4):223-232. doi:10.1080/14787210.2019.1584037
El Gendy FM, El-Mekkawy MS, Saleh NY, Habib MSE din, Younis FE. Clinical study of Presepsin and Pentraxin3 in critically ill children. Journal of Critical Care. 2018;47:36-40. doi:10.1016/j.jcrc.2018.06.004
Yoon SH, Kim EH, Kim HY, Ahn JG. Presepsin as a diagnostic marker of sepsis in children and adolescents: a systemic review and meta-analysis. BMC Infect Dis. 2019;19(1):760. doi:10.1186/s12879-019-4397-1
Hassuna NA, Elgezawy E, Mousa SO, et al. Diagnostic value of monocyte chemoattractant Protein-1, soluble mannose receptor, Presepsin, and Procalcitonin in critically ill children admitted with suspected sepsis. BMC Pediatr. 2021;21(1):458. doi:10.1186/s12887-021-02930-7
Plesko M, Suvada J, Makohusova M, et al. The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients. neo. 2016;63(05):752-760. doi:10.4149/neo_2016_512
Baraka A, Zakaria M. Presepsin as a diagnostic marker of bacterial infections in febrile neutropenic pediatric patients with hematological malignancies. Int J Hematol. 2018;108(2):184-191. doi:10.1007/s12185-018-2447-x
Agnello L, Bivona G, Parisi E, et al. Presepsin and Midregional Proadrenomedullin in Pediatric Oncologic Patients with Febrile Neutropenia. Laboratory Medicine. 2020;51(6):585-591. doi:10.1093/labmed/lmaa011
Curatola A, Lazzareschi I, Bersani G, Covino M, Gatto A, Chiaretti A. Impact of COVID‐19 outbreak in acute bronchiolitis: Lesson from a tertiary Italian Emergency Department. Pediatric Pulmonology. 2021;56(8):2484-2488. doi:10.1002/ppul.25442
Lazzerini M, Sforzi I, Trapani S, et al. Characteristics and risk factors for SARS-CoV-2 in children tested in the early phase of the pandemic: a cross-sectional study, Italy, 23 February to 24 May 2020. Eurosurveillance. 2021;26(14). doi:10.2807/1560-7917.ES.2021.26.14.2001248
Topcuoglu S, Arslanbuga C, Gursoy T, et al. Role of presepsin in the diagnosis of late-onset neonatal sepsis in preterm infants. The Journal of Maternal-Fetal & Neonatal Medicine. Published online July 2, 2015:1-6. doi:10.3109/14767058.2015.1064885
Sakyi SA, Enimil A, Adu DK, et al. Individual and combined bioscore model of presepsin, procalcitonin, and high sensitive C - reactive protein as biomarkers for early diagnosis of paediatric sepsis. Heliyon. 2020;6(9). doi:10.1016/J.HELIYON.2020.E04841
Bellos I, Fitrou G, Pergialiotis V, Thomakos N, Perrea DN, Daskalakis G. The diagnostic accuracy of presepsin in neonatal sepsis: a meta-analysis. Eur J Pediatr. 2018;177(5):625-632. doi:10.1007/s00431-018-3114-1
Ulla M., Pizzolato E., Lucchiari M., Loiacono M., Soardo F., Forno D., Morello F., Lupia E., Moiraghi C., Mengozzi G., et al. Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: A multicenter prospective study. Crit. Care. 2013;17:R168. doi: 10.1186/cc12847.
Balci C., Sungurtekin H., Gürses E., Sungurtekin U., Kaptanoğlu B. Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit. Crit. Care. 2002;7:85–90. doi: 10.1186/cc1843.
Sandquist M., Wong H.R. Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment. Expert Rev. Clin. Immunol. 2014;10:1349–1356. doi: 10.1586/1744666X.2014.949675.
Harbarth S., Holeckova K., Froidevaux C., Pittet D., Ricou B., Grau G.E., Vadas L., Pugin J., Network G.S. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am. J. Respir. Crit. Care Med. 2001;164:396–402. doi: 10.1164/ajrccm.164.3.2009052.
Yusa T., Tateda K., Ohara A., Miyazaki S. New possible biomarkers for diagnosis of infections and diagnostic distinction between bacterial and viral infections in children. J. Infect. Chemother. 2017;23:96–100. doi: 10.1016/j.jiac.2016.11.002.
Alizadeh N., Memar M.Y., Moaddab S.R., Kafil H.S. Aptamer-assisted novel technologies for detecting bacterial pathogens. Biomed. Pharmacother. 2017;93:737–745. doi: 10.1016/j.biopha.2017.07.011.
Leli C., Ferranti M., Marrano U., Al Dhahab Z.S., Bozza S., Cenci E., Mencacci A. Diagnostic accuracy of presepsin (sCD14-ST) and procalcitonin for prediction of bacteraemia and bacterial DNAaemia in patients with suspected sepsis. J. Med. Microbiol. 2016;65:713–719. doi: 10.1099/jmm.0.000278.
Bone R.C., Balk R.A., Cerra F.B., Dellinger R.P., Fein A.M., Knaus W.A., Schein R.M., Sibbald W.J. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1644–1655. doi: 10.1378/chest.101.6.1644.
Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.-D., Coopersmith C.M., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287.
Cecconi M., Evans L., Levy M., Rhodes A. Sepsis and septic shock. Lancet. 2018;392:75–87. doi: 10.1016/S0140-6736(18)30696-2.
Labib M., Berezovski M.V. Electrochemical aptasensors for microbial and viral pathogens. Adv. Biochem. Eng. Biotechnol. 2014;140:155–181. doi: 10.1007/10_2013_229.
Biron B.M., Ayala A., Lomas-Neira J.L. Biomarker insight biomarkers for sepsis: What is and what might be? Biomark Insights. 2015;10(Suppl. 4):7–17.
Pierrakos C., Vincent J.-L. Sepsis biomarkers: A review. Crit. Care. 2010;14:R15. doi: 10.1186/cc8872.
Chenevier-Gobeaux C., Borderie D., Weiss N., Mallet-Coste T., Claessens Y.-E. Presepsin (sCD14-ST), an innate immune response marker in sepsis. Clin. Chim. Acta. 2015;450:97–103. doi: 10.1016/j.cca.2015.06.026.
Zhang J., Hu Z.-D., Song J., Shao J. Diagnostic Value of Presepsin for Sepsis. A Systematic Review and Meta-Analysis. Medicine. 2015;94:e2158. doi: 10.1097/MD.0000000000002158.
Wu J., Hu L., Zhang G., Wu F., He T. Accuracy of Presepsin in Sepsis Diagnosis: A Systematic Review and Meta-Analysis. PLoS ONE. 2015;10:e0133057. doi: 10.1371/journal.pone.0133057.
Zheng Z., Jiang L., Ye L., Gao Y., Tang L., Zhang M. The accuracy of presepsin for the diagnosis of sepsis from SIRS: A systematic review and meta-analysis. Ann. Intensive Care. 2015;5:48. doi: 10.1186/s13613-015-0089-1.
Tong X., Cao Y., Yu M., Han C. Presepsin as a diagnostic marker for sepsis: Evidence from a bivariate meta-analysis. Ther. Clin. Risk Manag. 2015;11:1027–1033. doi: 10.2147/TCRM.S84811.
Liu Y., Hou J.-h., Li Q., Chen K.-j., Wang S.-N., Wang J.-m. Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome: A systematic review and meta-analysis. SpringerPlus. 2016;5:2091. doi: 10.1186/s40064-016-3591-5.
Wu C.-C., Lan H.-M., Han S.-T., Chaou C.-H., Yeh C.-F., Liu S.-H., Li C.-H., Blaney G.N., Liu Z.-Y., Chen K.-F. Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: A systematic review and meta-analysis. Ann. Intensiv. Care. 2017;7:1–16. doi: 10.1186/s13613-017-0316-z.
Yang H.S., Hur M., Yi A., Kim H., Lee S., Kim S.-N. Prognostic value of presepsin in adult patients with sepsis: Systematic review and meta-analysis. PLoS ONE. 2018;13:e0191486. doi: 10.1371/journal.pone.0191486.
Ruan L., Chen G.-Y., Liu Z., Zhao Y., Xu G.-Y., Li S.-F., Li C.-N., Chen L.-S., Tao Z. The combination of procalcitonin and C-reactive protein or presepsin alone improves the accuracy of diagnosis of neonatal sepsis: A meta-analysis and systematic review. Crit. Care. 2018;22:1–9. doi: 10.1186/s13054-018-2236-1.
Kondo Y., Umemura Y., Hayashida K., Hara Y., Aihara M., Yamakawa K. Diagnostic value of procalcitonin and presepsin for sepsis in critically ill adult patients: A systematic review and meta-analysis. J. Intensiv. Care. 2019;7:1–13. doi: 10.1186/s40560-019-0374-4.
Taneja R., Batra P. Biomarkers as point of care tests (POCT) in neonatal sepsis: A state of science review. J. Neonatal Perinat. Med. 2021;14:331–338. doi: 10.3233/NPM-200581.
Endo S., Suzuki Y., Takahashi G., Shozushima T., Ishikura H., Murai A., Nishida T., Irie Y., Miura M., Iguchi H., et al. Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study. J. Infect. Chemother. 2012;18:891–897. doi: 10.1007/s10156-012-0435-2.
Klouche K., Cristol J.P., Devin J., Gilles V., Kuster N., Larcher R., Amigues L., Corne P., Jonquet O., Dupuy A.M. Diagnostic and prognostic value of soluble CD14 subtype (Presepsin) for sepsis and community-acquired pneumonia in ICU patients. Ann. Intensive Care. 2016;6:1. doi: 10.1186/s13613-016-0160-6.
Gad G.I., Shinkar D.M., Kamel El-Din M.M., Nagi H.M. The Utility of Soluble CD14 Subtype in Early Diagnosis of Culture-Proven Early-Onset Neonatal Sepsis and Prediction of Outcome. Am. J. Perinatol. 2020;37:497–502. doi: 10.1055/s-0039-1683863.
Kumar J., Singh A. A Comparative Evaluation of Presepsin with Procalcitonin and CRP in Diagnosing Neonatal Sepsis: Correspondence. Indian J. Pediatr. 2019;86:313–314. doi: 10.1007/s12098-018-2744-7
Iskandar A., Arthamin M.Z., Indriana K., Anshory M., Hur M., Di Somma S., GREAT Network Comparison between presepsin and procalcitonin in early diagnosis of neonatal sepsis. J. Matern. Neonatal Med. 2019;32:3903–3908. doi: 10.1080/14767058.2018.1475643.
Pietrasanta C., Ronchi A., Vener C., Poggi C., Ballerini C., Testa L., Colombo R.M., Spada E., Dani C., Mosca F., et al. Presepsin (Soluble cd14 subtype) as an early marker of neonatal sepsis and septic shock: A prospective diagnostic trial. Antibiotics. 2021;10:580. doi: 10.3390/antibiotics10050580.
Mostafa R., Khoulouss S., Nea M. Detection of presepsin and surface CD-14 as a biomarker for early diagnosis of neonatal sepsis. J. Am. Sci. 2015;1111:104–116.
Saied Osman A., Goudah Awadallah M., Tabl Hael M. Presepsin as a novel diagnostic marker in neonatal septicemia. Egypt. J. Med. Microbiol. 2015;24:21–26. doi: 10.12816/0024924.
Pugni L., Pietrasanta C., Milani S., Vener C., Ronchi A., Falbo M., Arghittu M., Mosca F. Presepsin (soluble CD14 subtype): Reference ranges of a new sepsis marker in term and preterm neonates. PLoS ONE. 2015;10:e0146020.
Montaldo P., Rosso R., Santantonio A., Chello G., Giliberti P. Presepsin for the detection of early-onset sepsis in preterm newborns. Pediatr. Res. 2017;81:329–334. doi: 10.1038/pr.2016.217.
De Rose D.U., Perri A., Auriti C., Gallini F., Maggio L., Fiori B., D’Inzeo T., Spanu T., Vento G. Time to positivity of blood cultures could inform decisions on antibiotics administration in neonatal early-onset sepsis. Antibiotics. 2021;10:123. doi: 10.3390/antibiotics10020123.
Hincu M.A., Zonda G.I., Stanciu G.D., Nemescu D., Paduraru L. Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis. Children. 2020;7:309. doi: 10.3390/children7120309.
Popa T.O., Cimpoeşu D. Dorobăţ CM: Diagnostic and prognostic value of presepsin in the emergency department. Rev Med. Chir. Soc. Med. Nat. Iasi. 2015;119:69–76.
Liu B., Chen Y.-X., Yin Q., Zhao Y.-Z., Li C.-S. Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department. Crit. Care. 2013;17:R244. doi: 10.1186/cc13070.
Carpio R., Zapata J., Spanuth E., Hess G. Utility of presepsin (sCD14-ST) as a diagnostic and prognostic marker of sepsis in the emergency department. Clin. Chim. Acta. 2015;450:169–175. doi: 10.1016/j.cca.2015.08.013.
Kweon O.J., Choi J.-H., Park S.K., Park A.J. Usefulness of presepsin (sCD14 sub- type) measurements as a new marker for the diagnosis and prediction of disease severity of sepsis in the Korean population. J. Crit. Care. 2014;29:965–970. doi: 10.1016/j.jcrc.2014.06.014.
De Guadiana Romualdo L.G., Torrella P.E., González M.V., Sánchez R.J., Holgado A.H., Freire A.O., Acebes S.R., Otón M.D.A. Diagnostic accuracy of pre-sepsin (soluble CD14 subtype) for prediction of bacteremia in patients with systemic inflammatory response syndrome in the Emergency Department. Clin. Biochem. 2014;47:505–508. doi: 10.1016/j.clinbiochem.2014.02.011.
Romualdo L.G.D.G., Torrella P.E., Acebes S.R., Otón M.D.A., Sánchez R.J., Holgado A.H., Santos E.J., Freire A.O. Diagnostic accuracy of presepsin (sCD14-ST) as a biomarker of infection and sepsis in the emergency department. Clin. Chim. Acta. 2017;464:6–11. doi: 10.1016/j.cca.2016.11.003.
Mussap M., Puxeddu E., Puddu M., Ottonello G., Coghe F., Comite P., Cibecchini F., Fanos V. Soluble CD14 subtype (sCD14-ST) presepsin in premature and full term critically ill newborns with sepsis and SIRS. Clin. Chim. Acta. 2015;451:65–70. doi: 10.1016/j.cca.2015.07.025.
Sargentini V., Ceccarelli G., D’Alessandro M., Collepardo D., Morelli A., D’Egidio A., Mariotti S., Nicoletti A.M., Evangelista B., D’Ettorre G., et al. Presepsin as a potential marker for bacterial infection relapse in critical care patients. A preliminary study. Clin. Chem. Lab. Med. 2014;53:567–573. doi: 10.1515/cclm-2014-0119.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Lavinia Capossela, Gaia Margiotta, Serena Ferretti, Antonietta Curatola, Chiara Bertolaso, Lorenzo Di Sarno, Antonio Chiaretti, Antonio Gatto
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
How to Cite
