The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Biological Characteristics of Presepsin
5. Presepsin Plasmatic Levels and Renal Function
6. Methods to Measure Presepsin Plasma Levels
7. Accuracy of Presepsin in Detecting Sepsis in Adults and Children
- −
- Presepsin < 200 pg/mL—sepsis excluded;
- −
- Presepsin < 300 pg/mL—systemic infection improbable;
- −
- Presepsin < 500 pg/mL—sepsis probable;
- −
- Presepsin < 1000 pg/mL—significant risk of severe sepsis;
- −
- Presepsin ≥ 1000 pg/mL—high risk of severe sepsis/septic shock equivalent to a SOFA score ≥ 8.
8. Ranges of Reference Values in Neonates
9. Presepsin Compared to Other Immunologic Biomarkers
10. Presepsin for the Detection of Early-Onset and Late-Onset Sepsis
11. Prognostic Significance of Presepsin
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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5th Centile | 25th Centile | 50th Centile | 75th Centile | 95th Centile | |
---|---|---|---|---|---|
Term (>37 weeks GA)[n= 484] | 315 | 466 | 604 | 791 | 1178 |
Preterm (24–36 weeks GA)[n= 195] | 352 | 503 | 620 | 864 | 1370 |
Type of Study | Authors, Year | Country | Population | Cut-off Value of P-SEP (pg/mL) | AUC | Type of Sample | Assay | Conclusions |
---|---|---|---|---|---|---|---|---|
Referenceranges | ||||||||
Prospective | Pugni et al., 2015 [14] | Italy | 484 healthy term 195 healthy preterm (GA 24–36 w) | 604 (50th centile) 620 (50th centile) | N/A | Whole blood | CLEIA | P-SEP levels are higher in preterm than in at-term neonates |
Prospective | Ishii et al., 2018 [15] | Japan | 30 healthy term (GA > 37 w) | 318.5 (at birth) 180.5 (day 5) | N/A | Whole blood | CLEIA | P-SEP levels show physiological variation during early neonatal period |
Prospective | Poggi et al., 2020 [4] | Italy | 183 preterm (GA < 32 w) | 583 (0–6 h) 614 (12 h) 604 (24 h) 513 (48 h) 50th centile | N/A | Whole blood | CLEIA | P-SEP levels in preterm <32 weeks GA are affected by GA during first 24 h of life |
EOS | ||||||||
Case- control | Motalib et al., 2015 [16] | Egypt | 28 EOS 34 healthy | 672 | 0.95 | Serum | CLEIA | P-SEP is an accurate marker in detecting EOS |
Prospective | Ozdemir et al., 2016 [17] | Turkey | 29 EOS 40 healthy (term neonates) | 539 | 0.77 | Serum | CLEIA | P-SEP may be used a reliable and accurate marker for both diagnosis and follow-up of EOS |
Case- control | Montaldo et al., 2017 [10] | Italy | 32 EOS 38 healthy (GA < 34 w) | 788 | 0.97 | Serum | CLEIA | P-SEP is significantly higher in preterm infants with EOS compared with uninfected infants |
Prospective | Seliem and Sultan, 2018 [18] | Egypt | 76 EOS 212 healthy (GA 24–36 w) | 2231 | N/A | Umbilical cord blood | ELISA | Umbilical cord blood P-SEP is a predictor of EOS in preterm infants born to mothers with premature rupture of membranes |
LOS | ||||||||
Prospective | Poggi et al., 2015 [1] | Italy | 19 LOS 21 healthy (GA < 32 w) | 885 | 0.97 | Whole blood | CLEIA | P-SEP is an accurate marker for the diagnosis of LOS in preterm infants |
Case- control | Sabry et al., 2016 [19] | Egypt | 80 LOS 40 healthy | 722 | 0.99 | Serum | ELISA | P-SEP is an accurate marker for the diagnosis of LOS |
Prospective | Topcuoglu et al., 2016 [20] | Turkey | 42 LOS (GA < 34 w) | 800.5 | 0.86 | Plasma | CLEIA | P-SEP can used as a reliable biomarker for the diagnosis of and response to treatment in LOS |
Prospective | Astrawinata et al., 2017 [21] | Indonesia | 40 LOS in preterm 40 healthy | 406 | 0.89 | Whole blood | CLEIA | P-SEP is the earliest and best-performing marker of LOS for the prognosis of preterm neonatal mortality when compared to CRP and PCT |
EOS/LOS | ||||||||
Prospective | Mussap et al., 2015 [22] | Italy | 25 sepsis 25 SIRS 25 healthy | 600 | 0.99 | Whole blood | CLEIA | In critically ill neonates, P-SEP could help in diagnosis and follow-up of neonatal sepsis and non-bacterial SIRS |
Case- control | Saied Osman et al., 2015 [23] | Egypt | 40 sepsis 15 healthy (full-term) | 875 | 0.95 | Plasma | CLEIA | P-SEP is a novel diagnostic marker in neonatal sepsis |
Prospective | Mostafa et al., 2015 [24] | Egypt | 49 sepsis 29 healthy | 686 | 0.78 | Plasma | CLEIA | P-SEP is useful in neonatal sepsis |
N/A | Tabl et al., 2016 [25] | Egypt | 22 sepsis 28 non- infectious SIRS 20 healthy (term neonates) | 812 | 0.99 | Plasma | CLEIA | P-SEP can discriminate between infections and non-infectious inflammatory conditions |
Prospective | Xiao et al., 2016 [26] | China | 140 sepsis 53 healthy | 786 | 0.94 | Whole blood | CLEIA | PSEP is accurate in early identify neonatal hematosepsis; its diagnostic value is superior to other laboratory Biomarkers |
Prospective | Miyosawa et al., 2018 [27] | Japan | 13 sepsis 18 healthy (preterm) | 795 | 0.86 | Whole blood | CLEIA | P-SEP can discriminate between infections and non-infectious inflammatory conditions |
Prospective | Kumar, et al., 2018 [28] | India | 41 sepsis | 1800 | 0.90 | Plasma | CLEIA | P-SEP, in comparison with CRP and PCT, offers a better sensitivity and negative predictive value |
Prospective | Iskandar et al., 2018 [29] | Indonesia | 51 sepsis | 706.5 | 0.80 | Whole blood | CLEIA | In early diagnosis of neonatal sepsis, compared with procalcitonin, presepsin seems to provide a better diagnostic value |
Prospective | Hashem et al., 2020 [30] | Egypt | 133 sepsis 102 healthy | 686 | 0.88 | Plasma | CLEIA | Presepsin is a valuable early diagnostic and monitoring sepsis biomarker, with higher specificity compared to neutrophil CD64 (nCD64) |
Prospective | Pietrasanta et al., 2021 [31] | Italy | 58 infections 77 sepsis 24 septic shock | 987.5 | 0.86 | Whole blood | CLEIA | P-SEP is an early marker of neonatal sepsis severity, but does not support the early identification of neonates with positive blood culture |
Number of Studies Considered | Authors, Year | Country | Number of Infants Included | Cut-off Value of P-SEP (pg/mL) | AUC | Pooled Sensitivity | Pooled Specificity | Conclusions |
---|---|---|---|---|---|---|---|---|
11 studies | Bellos et al., 2018 [32] | Greece | 783 (391 sepsis vs. 392 controls) | <650 | 0.96 | 91% | 85% | Diagnostic accuracy of P-SEP resulted high in detecting neonatal sepsis |
650–850 | 0.99 | 91% | 97% | |||||
>850 | 0.97 | 90% | 86% | |||||
28 studies comparing CRP, PCT, CRP + PCT or P-SEP | Ruan et al., 2018 [33] | China | 2661 (1281 sepsis vs. 1380 controls) | 722 | 0.99 | 94% | 98% | The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis |
10 studies | Van Maldeghem et al., 2019 [34] | Holland | 1369 (89 EOS, 61 LOS, 209 EOS and LOS combined vs. 1010 controls) | 305–672 | 0.94 | 81% | 86% | P-SEP is a promising and rapid-responding diagnostic biomarker for EOS and LOS. The difference in pooled means between EOS and LOS underlines the importance of considering them as two different disease entities |
801–855 | N/A | 81% | 100% | |||||
9 studies | Parri et al., 2019 [35] | Italy | 3 studies including 268 infants | <600 | 0.81 | 93% | 81% | Even though it cannot be recommended as a single diagnostic test, P-SEP could be a helpful and valuable biomarker in neonates with suspected sepsis |
6 studies including 375 infants | >600 | 0.97 | 87% | 100% |
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Maddaloni, C.; De Rose, D.U.; Santisi, A.; Martini, L.; Caoci, S.; Bersani, I.; Ronchetti, M.P.; Auriti, C. The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review. Int. J. Mol. Sci. 2021, 22, 12154. https://doi.org/10.3390/ijms222212154
Maddaloni C, De Rose DU, Santisi A, Martini L, Caoci S, Bersani I, Ronchetti MP, Auriti C. The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review. International Journal of Molecular Sciences. 2021; 22(22):12154. https://doi.org/10.3390/ijms222212154
Chicago/Turabian StyleMaddaloni, Chiara, Domenico Umberto De Rose, Alessandra Santisi, Ludovica Martini, Stefano Caoci, Iliana Bersani, Maria Paola Ronchetti, and Cinzia Auriti. 2021. "The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review" International Journal of Molecular Sciences 22, no. 22: 12154. https://doi.org/10.3390/ijms222212154