Diagnostic Accuracy of Soluble CD14 (Presepsin) in Identifying Gram- Positive versus Gram-Negative Infections in Preterm Neonates with Early-Onset Sepsis

Diagnostic Accuracy of Soluble CD14 (Presepsin) in Identifying Gram- Positive versus Gram-Negative Infections in Preterm Neonates with Early-Onset Sepsis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Diagnostic Accuracy of Soluble CD14 (Presepsin) in Identifying Gram- Positive versus Gram-Negative Infections in Preterm Neonates with Early-Onset Sepsis Mariam John Amin Ibrahim, Heba Mohamed Atif Ismail, Ahmed Nasser Ibrahim Elkholy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7710057/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Identifying the type of bacterial infection in a timely manner is crucial for the successful treatment of newborns with sepsis. Because blood culture results are often delayed, early biomarkers are needed to promptly signal infection and potentially provide clues to differentiate between Gram-positive and Gram-negative infections, thereby guiding timely therapy. Presepsin (P-SEP) has recently gained attention as a promising biomarker, generated as a component of the immune system's reaction to bacterial infection. It acts as an early warning sign of sepsis in newborns and can be identified in the first phases of inflammation. Purpose To assess the accuracy of soluble CD14 (presepsin) in differentiating between Gram-positive and Gram-negative infections in preterm newborns with early-onset neonatal sepsis. Methods sixteen newborns with early-onset sepsis proven retrospectively by positive blood culture results were included in this prospective observational study. Serum presepsin levels were measured at day 1 and day 3 after diagnosis. Results Patients with gram-negative infections had significantly elevated P-SEP levels initially on the first day and at follow-up on the third day. At a cutoff value of ≥ 970 ng/L, serum P-SEP on day 3 yielded a 100% positive predictive value, an 87.5% sensitivity, a 100% specificity, and an 88.8% negative predictive value to accurately predict the presence of gram negative bacterial infection. Conclusion Presepsin is a useful early biomarker in preterm neonates with early-onset sepsis, showing good accuracy in differentiating Gram-positive from Gram-negative infections and supporting timely clinical decision-making. Clinical trial number: not applicable accuracy Soluble CD14 Presepsin early onset Neonatal Sepsis Preterm Neonates blood culture gram negative bacteria Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION After preterm birth and difficulties connected to the labor and delivery process, the third most common cause of infant mortality is neonatal sepsis. It causes 42% of deaths in the first week of life and 13% of all neonatal deaths. [ 1 ] Despite the usefulness of numerous diagnostic and treatment options, doctors caring for infected neonates in the age of multi-drug resistance, particularly in low- and middle-income countries, confront numerous obstacles when making judgements. They are still in need of new specific diagnostic and prognostic markers to identify the type of organism in infected patients who would benefit from targeted antibiotic therapy rather than empirical antibiotics. In low- and middle-income countries (LMICs), blood culture results are often associated with long turnaround times and delayed reporting, which limits their usefulness for guiding early management decisions. [ 2 , 3 , 4 ] As a bacterial molecular pattern recognition receptor, CD14 can recognize a variety of ligand groups from pathogens that are both Gram-positive and Gram-negative, including Lipopolysaccharides (LPS) from Gram-negative bacteria and peptidoglycans and lipoteichoic acid from Gram-positive bacteria. [ 5 ] It facilitates the toll-like receptor 4's processing of the endotoxin signal, which causes the discharge of several cytokines and encourages the initiation of a systemic inflammatory reaction. [ 6 ] Monocytes and macrophages, which are inflammatory cells, exhibit 2 types of CD14: a membrane-bound CD14 (mCD14) found on these cells and a soluble CD14 (sCD14), which is created when the membrane form of CD14 is shed in the plasma. The body's reaction to a bacterial infection includes the production of presepsin (P-SEP), a fragment with a size of 13 kDa called soluble CD14 subtype, (sCD14-ST) that is produced when plasma proteases cleave sCD14. [ 7 ] P-SEP is thought to promote monocyte phagocytosis and interact with B and T cells to modify a particular immunological response, while its exact role is still unknown. In the early phases of inflammation and sepsis, it dramatically rises in the bloodstream. As a result, P-SEP appeared to be an appropriate biomarker for the early diagnosis of EOS. [ 8 , 9 , 10 ] AIM OF THE WORK To assess the accuracy of soluble CD14 (presepsin) in differentiating between Gram-positive and Gram-negative infections in preterm newborns with early-onset neonatal sepsis. PATIENTS AND METHODS This research was an observational prospective study. It was conducted at NICUs of Ain-Shams University Hospital, Cairo, Egypt, from October of 2021 and October of 2022. The present study included 16 newly born infants preterm diagnosed to have early onset sepsis proven by blood culture. Neonates with serious congenital malformation, fetal hydrops, perinatal asphyxia and confirmed intrauterine infections (herpes, syphilis, CMV, rubella, and toxoplasmosis) were excluded from the study [ 12 ] . All participating patients received empirical antibiotic therapy according to the protocol in children’s hospitals' NICUs (ampicillin and gentamycin) until culture and sensitivity results appeared. Every patient underwent the following procedures: Complete history taking : Antenatal, Natal and Postnatal histories. Gestational age estimation and Anthropometric measurements were done at time of admission. Clinical examination was performed for symptoms and signs of sepsis. Laboratory investigations done included blood culture (BACTEC), human presepsin (P-SEP) was determined using the enzyme linked immunosorbent assay (ELISA) technique. Blood samples were withdrawn from all cases prior to beginning of antibiotics. Presepsin was measured again at 72 hours. Blood samples were withdrawn by the most skilled personnel in the facility, and no samples were stored to be used in any further research. Statistical Analysis The acquired data was coded, entered, and analyzed using Microsoft Excel software. The data was then analyzed using the Statistical Package for the Social Sciences (SPSS) program, version 28.0. Categorical variables were displayed as numbers and proportions, whereas quantitative continuous variables were displayed as mean and standard deviation for parametric data and median and interquartile range for nonparametric data. To determine whether differences and associations were significant, the following tests were employed the normality of data was assessed by visual inspection of their histograms, skewness and kurtosis statistics and standard errors. Levene's test was used to confirm that the variances in the samples were equal (homogeneity of variance); for parametric data, independent continuous variables were compared using the student's t-test.; the one-sample Kolmogorov-Smirnov or Shapiro-Wilk tests were used to test the variables; the variable is not normally distributed if (p value) < 0.05; and the variances are not equal if (p value) < 0.05. The P-value, or probability level, was set at less than 0.05 for outcomes that were statistically significant and less than 0.001 for those that were highly significant. Where appropriate, values for the 95 percent confidence interval (95% CI) and odds ratio (OR) were shown. Receiver Operating Characteristic (ROC) curves for P-SEP were analysed in order to identify the area under the curve (AUC) and the most accurate cut-off values. After that, all other research variables, including sensitivity, specificity, LR+, LR-, positive predictive value (PPV), and negative predictive value (NPV), were assessed, in order to predict type of organism. For each parameter, an exact 95% CI was computed. An optimum test index is indicated by an AUC of 1.0; a diagnostic test with no relevance has an AUC of 0.5. A diagnostic test is generally considered low value if its ROC-AUC falls between 0.5 and 0.7, medium value if it falls between 0.7 and 0.9, and excellent value if it falls beyond 0.9. A significant statistical difference was demonstrated by a P < 0.01 value. RESULTS A total of 135 newborns were qualified to take part in our research, 119 were excluded due to the presence of congenital anomalies, presence of intrauterine infections, declining to participate, blood culture negative or lost follow up (Fig. 1 ) More than half of the case, 61.11% of them were males and 38.88% were females. Mean ± SD of the gestational age was 32.58 ± 2.43. The mean ± SD of the mother ages was 29.31 ± 5.01, and most of the deliveries were by caesarean sections. Eight out of sixteen culture-proven EOS had gram-negative bacteria (50%) and seven out of sixteen had gram-positive bacteria (43.7%); The organism that was most common was coagulase-negative Staphylococcus. (4cases; 25%), klebsiella came next (3 cases, 18.7%), Enterococci (2 cases; 12.5%), Acinetobacter (2 cases; 12.5%), One case with Staphylococcus aureus (6.3%), MRSA (1 case; 6.3%), Enterobacter aerogenes (one case; 6.3%), Candida parapsilosis (one case; 6.3%), and a mix of Klebsiella and Acinetobacter (one case; 6.3%) (Table 1 , Fig. 2 ) . Patients with gram-negative infections had substantially greater P-SEP levels at baseline (day 1) and follow-up (day 3), than those with gram-positive infections (t = 2.352, p = 0.035; t = 3.810, p = 0.002 respectively). ( Table 2 ) . Table 2 P-SEP level according to Blood cultures result in septic neonates. Gram positive Cocci (N = 7) Gram negative bacilli (N = 8) Independent T test p-value P-SEP at baseline (ng/L) 780.0 ± 176.54 1028.75 ± 225.54 2.352 0.035 a P-SEP at follow up (ng/L) 754.28 ± 179.89 1041.25 ± 107.62 3.810 0.002 a Abbreviations: P-SEP, presepsin; a = p-value is significant < 0.05 . Further analysis of the presepsin levels on day1 and day 3 indicate that P-SEP on day 1 produced 75 percent sensitivity, 85.7% specificity, 85.7% positive predictive value, and 77.4% negative predictive value, and a cutoff value of > 920 ng/L, with an area under the curve of 0.813 (95% confidence interval 0.582–1.043). Serum P-SEP on day three, however, produced 87.5% sensitivity, 100% specificity, 100% positive predictive value, and 88.8% negative predictive value, and an area under the curve of 0.946 (95% confidence interval 0.830–1.063) at a threshold value of > 970 ng/L. It is apparent that P-SEP on day 3 achieved a better performance in the prediction of gram-negative infections in EOS over the P-SEP on day 1. The overall model quality of presepsin (P-SEP) as a predictor for Gram-negative infections in early-onset neonatal sepsis (EOS) improved markedly from day 1 to day 3. On day 1, presepsin showed poor discriminatory performance (0.53, close to chance level), while by day 3, its performance increased substantially (0.83), indicating good accuracy in differentiating Gram-negative infections. This suggests that presepsin levels on day 3 are more reliable for diagnostic evaluation than those on day 1. (Table 3 , Fig. 3 , 4 ). Table 3 Receiver-operating characteristics (ROC) curve analyses of presepsin as a predictor for gram-negative infections in patients with EOS. cutoff AUC SE 95% CI Sensitivity Specificity PPV NPV P-SEP in day 1 (ng/L) ≥ 920 0.813 0.117 0.582–1.043 75% 85.7% 85.7% 77.4% P-SEP in day 3 (ng/L) ≥ 970 0.946 0.059 0.830–1.063 87.5% 100% 100% 88.8% Abbreviations: P-SEP, presepsin; AUC, area under the curve; PPV, positive predictive value; CI, confidence interval, SE, standard error;NPV, negative predictive value; DISCUSSION In the NICU, premature newborns are far more susceptible to systemic infections. They struggle to fight infections because of their underdeveloped immune systems, which may be further weakened by a number of preterm birth-related conditions. [11] . The establishment of the type of bacterial infection is a timely crucial key point in proper management of preterm neonates which help tailor the appropriate antibiotic that should be used. The regrettable delay in bacterial culture data (The gold standard for diagnosing sepsis in newborns) make it challenging to design precise antibiotic therapy. Current available biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT), have not been validated for differentiating between Gram-positive and Gram-negative organisms in neonatal sepsis. [12,13,14] . Therefore, It would be valuable to have a sepsis marker that assists in giving a clue in differentiating between Gram-positive and Gram-negative infections to guide early therapeutic decisions in neonates. [12] . If a biomarker could provide an early clue as to whether a preterm neonate has a Gram-positive or Gram-negative infection, it could guide timely selection of targeted antibiotic regimens and help reduce unnecessary antibiotic exposure. The human P-SEP level has gained popularity as a diagnostic tool for both full-term and preterm newborns with EOS within the past ten years. [10, 15] . The relationship between the type of causative organism and various sepsis biomarkers has not been extensively studied. Therefore, we aimed to explore this aspect using presepsin (P-SEP) as a potential indicator. In studying The relationship between P-SEP and blood culture results, it was revealed that P-SEP levels at days 1 and 3 were significantly higher in bacterial infections that were gram-negative than those that were gram-positive. (p = 0.035 and 0.002, respectively). Furthermore, P-SEP at follow up on day 3 of admission showed very good performance for identifying the presence of gram-negative infection, at a cutoff value of ≥ 970 ng/L [87.5% sensitivity, specificity 100%, PPV 100 %, NPV 88.8%]. However, at the cutoff value ≥ 920 ng/L, the P-SEP level at baseline on admission had [sensitivity 75%, specificity 85.7%, PPV = 85.7%, NPV = 77.4%]. In comparison to the P-SEP on day 1, the P-SEP on day 3 had better performance, having a PPV of 100% vs. 85.7% and a sensitivity of 87.5% vs. 75%. These results were in line with those of Masson et al., who found that patients with Gram-negative bacterial infections had greater baseline P-SEP levels (946 ng/L) than patients with Gram-positive infections [16] . Mahmoud Zayed et al. found that gram-positive infections had greater P-SEP levels at days 1, 3, and 6 of life than gram-negative infections, which is inconsistent to our findings. [17] . But according to some prior studies, there is no discernible difference between gram-positive and gram-negative infections in terms of P-SEP on days 1 and 3 [18,19] . The 13 kDa subtype of the soluble CD14 on the N-terminal segment is the presepsin we have been measuring in our study. CD14 is expressed on the membrane of phagocytic cells and serves as a pattern recognition receptor (PRR) for lipopolysaccharide (LPS)/LPS-binding protein (LPS-LBP) complexes. Together with the bacteria that are ingested, CD14 is internalized during phagocytosis. It is then cleaved via phago-lysosomal processing and is released into the plasma as presepsin. The presence of lipopolysaccharide (LPS), a characteristic part of Gram-negative bacteria, may help to explain why infections brought on by Gram-negative bacteria have higher presepsin levels than those produced by Gram-positive bacteria [20] . This study has several noteworthy limitations. It was conducted at a single center with a relatively small sample size, which restricts the generalizability of the findings. In addition, to the discrepancies in reported reference values for presepsin, particularly in preterm neonates. We recommend that future research be conducted on a larger scale and across multiple centers to more accurately evaluate the role of presepsin in differentiating Gram-positive from Gram-negative infections. CONCLUSION Presepsin evaluation in preterm neonates with early-onset sepsis demonstrates diagnostic value as an early biomarker of infection. While it cannot replace blood culture, presepsin shows promising accuracy in differentiating between Gram-positive and Gram-negative infections, supporting its role as a useful adjunct for guiding timely therapeutic decisions in neonatal intensive care. Abbreviations AUC: area under the curve After that, all other research variables, including sensitivity, specificity, CI: confidence interval CMV: Cytomegalovirus. CONS: coagulase negative staphylococcus. CRP: C- reactive protein ELISA: enzyme linked immunosorbent assay EOS: early onset sepsis kDa: kilodalton LPS-LBP: lipopolysaccharide/LPS-binding protein complexes LPS: Lipopolysaccharides mCD14: membrane-bound CD14 MRSA: methicillin-resistant staphylococcus aureus NICUs: neonatal intensive care units. NPV: negative predictive value OR: odds ratio P-SEP: Presepsin pattern recognition receptor (PRR) for PPV: positive predictive value ROC: Receiver Operating Characteristic sCD14-ST : soluble CD14 subtype soluble CD14 (sCD14 SPSS: Statistical Package for the Social Sciences program Declarations Ethical approval and consent to participate The study received approval from the faculty of medicine's Research Ethics Committee, Ain Shams university no. MS 619/2021. This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki, as adopted by the World Medical Association for research involving human participants. Each patient's parents provided their informed consent to be recruited in the study. No personal data was used in the study. The participants had the write to withdraw at any point in the study. Consent for publication N/A no personal data was used in this research Availability of data and materials The data supporting the findings of this research are available from the corresponding author and can be provided upon reasonable request Competing interests The authors declare that they have no conflicts of interest. Funding This research received no external funding. Authors contribution All authors contributed to the formulation of the study design. AE was responsible for the collection of clinical data. The first draft of the manuscript was prepared by MI and AE. All authors reviewed and commented on previous versions of the manuscript and have read and approved the final version. Acknowledgements We gratefully acknowledge all the participants who generously contributed to this study. Their involvement was invaluable to the success of our research. References Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379(9832):2151-61. Zea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr. 2015;61(1):1-13. Sands K, Spiller O, Thomson K, Portal E, Iregbu K, Walsh T. Early-onset neonatal sepsis in low- and middle-income countries: Current challenges and future opportunities. Infect Drug Resist. 2022;15:933-46. Kabugo D, Asiimwe BB, Dowdy DW, et al. Best practices of blood cultures in low- and middle-income countries. Clin Microbiol Rev. 2020;33(2):e00146-19. 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. 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):625-32. Seliem W, Sultan AM. Presepsin as a predictor of early onset neonatal sepsis in the umbilical cord blood of premature infants with premature rupture of membranes. Pediatr Int. 2018;60(5):428-32. Memar MY, Alizadeh N, Varshochi M, Kafil HS. Immunologic biomarkers for diagnostic of early-onset neonatal sepsis. J Matern Fetal Neonatal Med. 2019;32(1):143-53. Memar MY, Baghi HB. Presepsin: A promising biomarker for the detection of bacterial infections. Biomed Pharmacother. 2019;111:649-56. 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. Melville JM, Moss TJM. The immune consequences of preterm birth. Front Neurosci. 2013;7:79. Polin RA, Papile LA, Baley J, Bhutani VK, Carlo WA, Cummings J, Kumar P, Tan RC, Wang KS; Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129(5):1006-15. Hofer N, Zacharias E, Müller W, Resch B. An update on the use of C-reactive protein in early-onset neonatal sepsis: Current insights and new tasks. Neonatology. 2012;102(1):25-36. Stocker M, van Herk W, el Helou S, et al. Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: A multicentre, randomized controlled trial (NeoPIns). Lancet. 2017;390(10097):871-81. Botondi V, D’Adamo E, Plebani M, Trubiani O, Perrotta M, Di Ricco L, Spagnuolo C, De Sanctis S, Barbante E, Strozzi MC. Perinatal presepsin assessment: A new sepsis diagnostic tool? Clin Chem Lab Med. 2022;60(8):1136-44. Masson S, Caironi P, Fanizza C, Thomae R, Bernasconi R, Noto A, Oggioni R, Pasetti GS, Romero M, Tognoni G. Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: Data from the multicenter, randomized ALBIOS trial. Intensive Care Med. 2015;41(1):12-20. Mahmoud Zayed K, Abd Elmoez Ali Saad A, Mohamed Amin W, Gamal Abo El-Nasr M. Diagnostic value of presepsin in detection of early-onset neonatal sepsis. Al-Azhar J Pediatr. 2020;23(2):825-51. Asmaa OA, Hanan H, Al-Shaimaa MS, Atya AMA. Presepsin: A new marker for early diagnosis of septicemia. Med J Cairo Univ. 2018;86(9):2237. Değirmencioğlu H, Ozer Bekmez B, Derme T, Öncel MY, Canpolat FE, Tayman C. Presepsin and fetuin-A dyad for the diagnosis of proven sepsis in preterm neonates. BMC Infect Dis. 2019;19(1):1-7. Koizumi Y, Sakanashi D, Mohri T, Watanabe H, Shiota A, Asai N, Kato H, Hagihara M, Murotani K, Yamagishi Y, Suematsu H, Mikamo H. Can presepsin uniformly respond to various pathogens? An in vitro assay of new sepsis marker. BMC Immunol. 2020;21(1):33. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7710057","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":542278909,"identity":"7a338843-0581-4909-876d-8a46ccf5b185","order_by":0,"name":"Mariam John Amin 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16:21:32","extension":"html","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":78596,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7710057/v1/324d7bcef3f951cb725dc3a7.html"},{"id":95567093,"identity":"5589d05f-511f-4f69-b1dc-5bc42396c27c","added_by":"auto","created_at":"2025-11-10 16:21:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":31526,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003econsort of the studied neonates\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7710057/v1/aef4ea238fe079975bbf5aa9.png"},{"id":95655584,"identity":"5927a1c9-5916-4cd0-9a00-241469c5f169","added_by":"auto","created_at":"2025-11-11 16:16:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":93849,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBlood culture results in septic neonates.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7710057/v1/c4c0a96b0cb8c9cf4051630a.png"},{"id":95567111,"identity":"9cdfc9b2-cea8-4bf2-bc11-1e17ddaeea5f","added_by":"auto","created_at":"2025-11-10 16:21:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":69235,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe overall model quality of P-SEP as a predictor for infections with gram negative organisms in EOS.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7710057/v1/7125bdaa0f676594e7bd5195.png"},{"id":95655691,"identity":"10fe6e70-41dd-48e3-a554-1860b9680d3a","added_by":"auto","created_at":"2025-11-11 16:16:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":74528,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC curve for prediction of infections with gram negative organisms in EOS.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7710057/v1/2709c7a4c36fb6a0d022bff6.png"},{"id":104768134,"identity":"8b2acd5e-3ac8-4384-a6e3-f24e4b5f8b46","added_by":"auto","created_at":"2026-03-17 04:10:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2340662,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7710057/v1/53d6516d-1a3c-4c53-a403-c3c4de06ce1a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic Accuracy of Soluble CD14 (Presepsin) in Identifying Gram- Positive versus Gram-Negative Infections in Preterm Neonates with Early-Onset Sepsis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAfter preterm birth and difficulties connected to the labor and delivery process, the third most common cause of infant mortality is neonatal sepsis. It causes 42% of deaths in the first week of life and 13% of all neonatal deaths. \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eDespite the usefulness of numerous diagnostic and treatment options, doctors caring for infected neonates in the age of multi-drug resistance, particularly in low- and middle-income countries, confront numerous obstacles when making judgements. They are still in need of new specific diagnostic and prognostic markers to identify the type of organism in infected patients who would benefit from targeted antibiotic therapy rather than empirical antibiotics. In low- and middle-income countries (LMICs), blood culture results are often associated with long turnaround times and delayed reporting, which limits their usefulness for guiding early management decisions. \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAs a bacterial molecular pattern recognition receptor, CD14 can recognize a variety of ligand groups from pathogens that are both Gram-positive and Gram-negative, including Lipopolysaccharides (LPS) from Gram-negative bacteria and peptidoglycans and lipoteichoic acid from Gram-positive bacteria. \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e It facilitates the toll-like receptor 4's processing of the endotoxin signal, which causes the discharge of several cytokines and encourages the initiation of a systemic inflammatory reaction. \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eMonocytes and macrophages, which are inflammatory cells, exhibit 2 types of CD14: a membrane-bound CD14 (mCD14) found on these cells and a soluble CD14 (sCD14), which is created when the membrane form of CD14 is shed in the plasma. The body's reaction to a bacterial infection includes the production of presepsin (P-SEP), a fragment with a size of 13 kDa called soluble CD14 subtype, (sCD14-ST) that is produced when plasma proteases cleave sCD14. \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eP-SEP is thought to promote monocyte phagocytosis and interact with B and T cells to modify a particular immunological response, while its exact role is still unknown. In the early phases of inflammation and sepsis, it dramatically rises in the bloodstream. As a result, P-SEP appeared to be an appropriate biomarker for the early diagnosis of EOS. \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n\u003ch3\u003eAIM OF THE WORK\u003c/h3\u003e\n\u003cp\u003eTo assess the accuracy of soluble CD14 (presepsin) in differentiating between Gram-positive and Gram-negative infections in preterm newborns with early-onset neonatal sepsis.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cp\u003eThis research was an observational prospective study. It was conducted at NICUs of Ain-Shams University Hospital, Cairo, Egypt, from October of 2021 and October of 2022.\u003c/p\u003e\u003cp\u003eThe present study included 16 newly born infants preterm diagnosed to have early onset sepsis proven by blood culture. Neonates with serious congenital malformation, fetal hydrops, perinatal asphyxia and confirmed intrauterine infections (herpes, syphilis, CMV, rubella, and toxoplasmosis) were excluded from the study \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. All participating patients received empirical antibiotic therapy according to the protocol in children’s hospitals' NICUs (ampicillin and gentamycin) until culture and sensitivity results appeared.\u003c/p\u003e\u003cp\u003eEvery patient underwent the following procedures: \u003cem\u003eComplete history taking\u003c/em\u003e: Antenatal, Natal and Postnatal histories. Gestational age estimation and Anthropometric measurements were done at time of admission. Clinical examination was performed for symptoms and signs of sepsis. Laboratory investigations done included blood culture (BACTEC), human presepsin (P-SEP) was determined using the enzyme linked immunosorbent assay (ELISA) technique. Blood samples were withdrawn from all cases prior to beginning of antibiotics. Presepsin was measured again at 72 hours. Blood samples were withdrawn by the most skilled personnel in the facility, and no samples were stored to be used in any further research.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThe acquired data was coded, entered, and analyzed using Microsoft Excel software. The data was then analyzed using the Statistical Package for the Social Sciences (SPSS) program, version 28.0. Categorical variables were displayed as numbers and proportions, whereas quantitative continuous variables were displayed as mean and standard deviation for parametric data and median and interquartile range for nonparametric data.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTo determine whether differences and associations were significant, the following tests were employed\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ethe normality of data was assessed by visual inspection of their histograms, skewness and kurtosis statistics and standard errors. Levene's test was used to confirm that the variances in the samples were equal (homogeneity of variance); for parametric data, independent continuous variables were compared using the student's t-test.; the one-sample Kolmogorov-Smirnov or Shapiro-Wilk tests were used to test the variables; the variable is not normally distributed if (p value) \u0026lt; 0.05; and the variances are not equal if (p value) \u0026lt; 0.05.\u003c/p\u003e\u003cp\u003eThe P-value, or probability level, was set at less than 0.05 for outcomes that were statistically significant and less than 0.001 for those that were highly significant. Where appropriate, values for the 95 percent confidence interval (95% CI) and odds ratio (OR) were shown.\u003c/p\u003e\u003cp\u003eReceiver Operating Characteristic (ROC) curves for P-SEP were analysed in order to identify the area under the curve (AUC) and the most accurate cut-off values. After that, all other research variables, including sensitivity, specificity, LR+, LR-, positive predictive value (PPV), and negative predictive value (NPV), were assessed, in order to predict type of organism. For each parameter, an exact 95% CI was computed. An optimum test index is indicated by an AUC of 1.0; a diagnostic test with no relevance has an AUC of 0.5. A diagnostic test is generally considered low value if its ROC-AUC falls between 0.5 and 0.7, medium value if it falls between 0.7 and 0.9, and excellent value if it falls beyond 0.9. A significant statistical difference was demonstrated by a P \u0026lt; 0.01 value.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003c/p\u003e\u003cp\u003e A total of 135 newborns were qualified to take part in our research, 119 were excluded due to the presence of congenital anomalies, presence of intrauterine infections, declining to participate, blood culture negative or lost follow up (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eMore than half of the case, 61.11% of them were males and 38.88% were females. Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of the gestational age was 32.58\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD of the mother ages was 29.31\u0026thinsp;\u0026plusmn;\u0026thinsp;5.01, and most of the deliveries were by caesarean sections.\u003c/p\u003e\u003cp\u003eEight out of sixteen culture-proven EOS had gram-negative bacteria (50%) and seven out of sixteen had gram-positive bacteria (43.7%); The organism that was most common was coagulase-negative Staphylococcus. (4cases; 25%), klebsiella came next (3 cases, 18.7%), Enterococci (2 cases; 12.5%), Acinetobacter (2 cases; 12.5%), One case with Staphylococcus aureus (6.3%), MRSA (1 case; 6.3%), Enterobacter aerogenes (one case; 6.3%), Candida parapsilosis (one case; 6.3%), and a mix of Klebsiella and Acinetobacter (one case; 6.3%) \u003cb\u003e(Table\u0026nbsp;1\u003c/b\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePatients with gram-negative infections had substantially greater P-SEP levels at baseline (day 1) and follow-up (day 3), than those with gram-positive infections (t\u0026thinsp;=\u0026thinsp;2.352, p\u0026thinsp;=\u0026thinsp;0.035; t\u0026thinsp;=\u0026thinsp;3.810, p\u0026thinsp;=\u0026thinsp;0.002 respectively). \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eP-SEP level according to Blood cultures result in septic neonates.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGram positive Cocci\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGram negative bacilli\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIndependent T test\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP-SEP at baseline (ng/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e780.0\u0026thinsp;\u0026plusmn;\u0026thinsp;176.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1028.75\u0026thinsp;\u0026plusmn;\u0026thinsp;225.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.352\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP-SEP at follow up (ng/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e754.28\u0026thinsp;\u0026plusmn;\u0026thinsp;179.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1041.25\u0026thinsp;\u0026plusmn;\u0026thinsp;107.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.810\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: P-SEP, presepsin; \u003csup\u003ea\u003c/sup\u003e = p-value is significant\u0026thinsp;\u0026lt;\u0026thinsp;0.05 .\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFurther analysis of the presepsin levels on day1 and day 3 indicate that P-SEP on day 1 produced 75 percent sensitivity, 85.7% specificity, 85.7% positive predictive value, and 77.4% negative predictive value, and a cutoff value of \u0026gt;\u0026thinsp;920 ng/L, with an area under the curve of 0.813 (95% confidence interval 0.582\u0026ndash;1.043). Serum P-SEP on day three, however, produced 87.5% sensitivity, 100% specificity, 100% positive predictive value, and 88.8% negative predictive value, and an area under the curve of 0.946 (95% confidence interval 0.830\u0026ndash;1.063) at a threshold value of \u0026gt;\u0026thinsp;970 ng/L. It is apparent that P-SEP on day 3 achieved a better performance in the prediction of gram-negative infections in EOS over the P-SEP on day 1. The overall model quality of presepsin (P-SEP) as a predictor for Gram-negative infections in early-onset neonatal sepsis (EOS) improved markedly from day 1 to day 3. On day 1, presepsin showed poor discriminatory performance (0.53, close to chance level), while by day 3, its performance increased substantially (0.83), indicating good accuracy in differentiating Gram-negative infections. This suggests that presepsin levels on day 3 are more reliable for diagnostic evaluation than those on day 1. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e,\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eReceiver-operating characteristics (ROC) curve analyses of presepsin as a predictor for gram-negative infections in patients with EOS.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ecutoff\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAUC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSensitivity\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSpecificity\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePPV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNPV\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP-SEP in day 1 (ng/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;920\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.813\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.117\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.582\u0026ndash;1.043\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e75%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e85.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e85.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e77.4%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP-SEP in day 3 (ng/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;970\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.946\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.059\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.830\u0026ndash;1.063\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e87.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e100%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e100%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e88.8%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eAbbreviations: P-SEP, presepsin; AUC, area under the curve; PPV, positive predictive value; CI, confidence interval, SE, standard error;NPV, negative predictive value;\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn the NICU, premature newborns are far more susceptible to systemic infections. They struggle to fight infections because of their underdeveloped immune systems, which may be further weakened by a number of preterm birth-related conditions. \u003csup\u003e[11]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe establishment of the type of bacterial infection is a timely crucial key point in proper management of preterm neonates which help tailor the appropriate antibiotic that should be used. The regrettable delay in bacterial culture data (The gold standard for diagnosing sepsis in newborns) make it challenging to design precise antibiotic therapy. Current available biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT), have not been validated for differentiating between Gram-positive and Gram-negative organisms in neonatal sepsis.\u003csup\u003e\u0026nbsp;[12,13,14]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTherefore, It would be valuable to have a sepsis marker that assists in giving a clue in differentiating between Gram-positive and Gram-negative infections to guide early therapeutic decisions in neonates.\u003csup\u003e\u0026nbsp;[12]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIf a biomarker could provide an early clue as to whether a preterm neonate has a Gram-positive or Gram-negative infection, it could guide timely selection of targeted antibiotic regimens and help reduce unnecessary antibiotic exposure.\u003c/p\u003e\n\u003cp\u003eThe human P-SEP level has gained popularity as a diagnostic tool for both full-term and preterm newborns with EOS within the past ten years. \u003csup\u003e[10, 15]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe relationship between the type of causative organism and various sepsis biomarkers has not been extensively studied. Therefore, we aimed to explore this aspect using presepsin (P-SEP) as a potential indicator.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn studying The relationship between P-SEP and blood culture results, it was revealed that P-SEP levels at days 1 and 3 were significantly higher in bacterial infections that were gram-negative than those that were gram-positive. (p = 0.035 and 0.002, respectively).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, P-SEP at follow up on day 3 of admission showed very good performance for identifying the presence of gram-negative infection, at a cutoff value of ≥ 970 ng/L [87.5% sensitivity, specificity 100%, PPV 100 %, NPV 88.8%]. However, at the cutoff value ≥ 920 ng/L, the P-SEP level at baseline on admission had [sensitivity 75%, specificity 85.7%, PPV = 85.7%, NPV = 77.4%].\u003c/p\u003e\n\u003cp\u003eIn comparison to the P-SEP on day 1, the P-SEP on day 3 had better performance, having a PPV of 100% vs. 85.7% and a sensitivity of 87.5% vs. 75%.\u003c/p\u003e\n\u003cp\u003eThese results were in line with those of Masson et al., who found that patients with Gram-negative bacterial infections had greater baseline P-SEP levels (946 ng/L) than patients with Gram-positive infections \u003csup\u003e[16]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMahmoud Zayed et al.\u003c/strong\u003e found that gram-positive infections had greater P-SEP levels at days 1, 3, and 6 of life than gram-negative infections, which is inconsistent to our findings. \u003csup\u003e[17]\u003c/sup\u003e. But according to some prior studies, there is no discernible difference between gram-positive and gram-negative infections in terms of P-SEP on days 1 and 3 \u003csup\u003e[18,19]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe 13 kDa subtype of the soluble CD14 on the N-terminal segment is the presepsin we have been measuring in our study. CD14 is expressed on the membrane of phagocytic cells and serves as a pattern recognition receptor (PRR) for lipopolysaccharide (LPS)/LPS-binding protein (LPS-LBP) complexes. Together with the bacteria that are ingested, CD14 is internalized during phagocytosis. It is then cleaved via phago-lysosomal processing and is released into the plasma as presepsin. The presence of lipopolysaccharide (LPS), a characteristic part of Gram-negative bacteria, may help to explain why infections brought on by Gram-negative bacteria have higher presepsin levels than those produced by Gram-positive bacteria \u003csup\u003e[20]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThis study has several noteworthy limitations. It was conducted at a single center with a relatively small sample size, which restricts the generalizability of the findings. In addition, to the discrepancies in reported reference values for presepsin, particularly in preterm neonates. We recommend that future research be conducted on a larger scale and across multiple centers to more accurately evaluate the role of presepsin in differentiating Gram-positive from Gram-negative infections.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003ePresepsin evaluation in preterm neonates with early-onset sepsis demonstrates diagnostic value as an early biomarker of infection. While it cannot replace blood culture, presepsin shows promising accuracy in differentiating between Gram-positive and Gram-negative infections, supporting its role as a useful adjunct for guiding timely therapeutic decisions in neonatal intensive care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAUC: area under the curve After that, all other research variables, including sensitivity, specificity,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCI: confidence interval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCMV: Cytomegalovirus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CONS: coagulase negative staphylococcus.\u003c/p\u003e\n\u003cp\u003eCRP: C- reactive protein\u003c/p\u003e\n\u003cp\u003eELISA: enzyme linked immunosorbent assay\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEOS: early onset sepsis\u003c/p\u003e\n\u003cp\u003ekDa: kilodalton\u003c/p\u003e\n\u003cp\u003eLPS-LBP: \u0026nbsp;lipopolysaccharide/LPS-binding protein complexes\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLPS: Lipopolysaccharides\u0026nbsp;\u003c/p\u003e\n\u003cp\u003emCD14: membrane-bound CD14\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMRSA: methicillin-resistant staphylococcus aureus\u003c/p\u003e\n\u003cp\u003eNICUs: neonatal intensive care units.\u003c/p\u003e\n\u003cp\u003eNPV: negative predictive value\u003c/p\u003e\n\u003cp\u003eOR: odds ratio\u003c/p\u003e\n\u003cp\u003eP-SEP: Presepsin\u003c/p\u003e\n\u003cp\u003epattern recognition receptor (PRR) for\u003c/p\u003e\n\u003cp\u003ePPV: positive predictive value\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eROC: Receiver Operating Characteristic\u0026nbsp;\u003c/p\u003e\n\u003cp\u003esCD14-ST : soluble CD14 subtype\u003c/p\u003e\n\u003cp\u003esoluble CD14 (sCD14\u003c/p\u003e\n\u003cp\u003eSPSS: Statistical Package for the Social Sciences program\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received approval from the faculty of medicine's Research Ethics Committee, Ain Shams university no. MS 619/2021. This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki, as adopted by the World Medical Association for research involving human participants. Each patient's parents provided their informed consent to be recruited in the study. No personal data was used in the study. The participants had the write to withdraw at any point in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN/A no personal data was used in this research\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this research are available from the corresponding author and can be provided upon reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the formulation of the study design. AE was responsible for the collection of clinical data. The first draft of the manuscript was prepared by MI and AE. All authors reviewed and commented on previous versions of the manuscript and have read and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully acknowledge all the participants who generously contributed to this study. Their involvement was invaluable to the success of our research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e\u003cstrong\u003eLiu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379(9832):2151-61.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eZea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr. 2015;61(1):1-13.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eSands K, Spiller O, Thomson K, Portal E, Iregbu K, Walsh T. Early-onset neonatal sepsis in low- and middle-income countries: Current challenges and future opportunities. Infect Drug Resist. 2022;15:933-46.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eKabugo D, Asiimwe BB, Dowdy DW, et al. Best practices of blood cultures in low- and middle-income countries. Clin Microbiol Rev. 2020;33(2):e00146-19.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMussap 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.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eBellos 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):625-32.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eSeliem W, Sultan AM. Presepsin as a predictor of early onset neonatal sepsis in the umbilical cord blood of premature infants with premature rupture of membranes. Pediatr Int. 2018;60(5):428-32.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMemar MY, Alizadeh N, Varshochi M, Kafil HS. Immunologic biomarkers for diagnostic of early-onset neonatal sepsis. J Matern Fetal Neonatal Med. 2019;32(1):143-53.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMemar MY, Baghi HB. Presepsin: A promising biomarker for the detection of bacterial infections. Biomed Pharmacother. 2019;111:649-56.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003ePoggi 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.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMelville JM, Moss TJM. The immune consequences of preterm birth. Front Neurosci. 2013;7:79.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003ePolin RA, Papile LA, Baley J, Bhutani VK, Carlo WA, Cummings J, Kumar P, Tan RC, Wang KS; Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129(5):1006-15.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eHofer N, Zacharias E, M\u0026uuml;ller W, Resch B. An update on the use of C-reactive protein in early-onset neonatal sepsis: Current insights and new tasks. Neonatology. 2012;102(1):25-36.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eStocker M, van Herk W, el Helou S, et al. Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: A multicentre, randomized controlled trial (NeoPIns). Lancet. 2017;390(10097):871-81.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eBotondi V, D\u0026rsquo;Adamo E, Plebani M, Trubiani O, Perrotta M, Di Ricco L, Spagnuolo C, De Sanctis S, Barbante E, Strozzi MC. Perinatal presepsin assessment: A new sepsis diagnostic tool? Clin Chem Lab Med. 2022;60(8):1136-44.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMasson S, Caironi P, Fanizza C, Thomae R, Bernasconi R, Noto A, Oggioni R, Pasetti GS, Romero M, Tognoni G. Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: Data from the multicenter, randomized ALBIOS trial. Intensive Care Med. 2015;41(1):12-20.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMahmoud Zayed K, Abd Elmoez Ali Saad A, Mohamed Amin W, Gamal Abo El-Nasr M. Diagnostic value of presepsin in detection of early-onset neonatal sepsis. Al-Azhar J Pediatr. 2020;23(2):825-51.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAsmaa OA, Hanan H, Al-Shaimaa MS, Atya AMA. Presepsin: A new marker for early diagnosis of septicemia. Med J Cairo Univ. 2018;86(9):2237.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eDeğirmencioğlu H, Ozer Bekmez B, Derme T, \u0026Ouml;ncel MY, Canpolat FE, Tayman C. Presepsin and fetuin-A dyad for the diagnosis of proven sepsis in preterm neonates. BMC Infect Dis. 2019;19(1):1-7.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eKoizumi Y, Sakanashi D, Mohri T, Watanabe H, Shiota A, Asai N, Kato H, Hagihara M, Murotani K, Yamagishi Y, Suematsu H, Mikamo H. Can presepsin uniformly respond to various pathogens? An in vitro assay of new sepsis marker. BMC Immunol. 2020;21(1):33.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"accuracy, Soluble CD14, Presepsin, early onset Neonatal Sepsis, Preterm Neonates, blood culture, gram negative bacteria","lastPublishedDoi":"10.21203/rs.3.rs-7710057/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7710057/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIdentifying the type of bacterial infection in a timely manner is crucial for the successful treatment of newborns with sepsis. Because blood culture results are often delayed, early biomarkers are needed to promptly signal infection and potentially provide clues to differentiate between Gram-positive and Gram-negative infections, thereby guiding timely therapy. Presepsin (P-SEP) has recently gained attention as a promising biomarker, generated as a component of the immune system's reaction to bacterial infection. It acts as an early warning sign of sepsis in newborns and can be identified in the first phases of inflammation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the accuracy of soluble CD14 (presepsin) in differentiating between Gram-positive and Gram-negative infections in preterm newborns with early-onset neonatal sepsis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003esixteen newborns with early-onset sepsis proven retrospectively by positive blood culture results were included in this prospective observational study. Serum presepsin levels were measured at day 1 and day 3 after diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with gram-negative infections had significantly elevated P-SEP levels initially on the first day and at follow-up on the third day. At a cutoff value of ≥ 970 ng/L, serum P-SEP on day 3 yielded a 100% positive predictive value, an 87.5% sensitivity, a 100% specificity, and an 88.8% negative predictive value to accurately predict the presence of gram negative bacterial infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePresepsin is a useful early biomarker in preterm neonates with early-onset sepsis, showing good accuracy in differentiating Gram-positive from Gram-negative infections and supporting timely clinical decision-making.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number: not applicable\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Diagnostic Accuracy of Soluble CD14 (Presepsin) in Identifying Gram- Positive versus Gram-Negative Infections in Preterm Neonates with Early-Onset Sepsis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 16:21:27","doi":"10.21203/rs.3.rs-7710057/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c150c51d-7570-4737-9c0e-a6fb35d0309b","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-17T04:09:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-10 16:21:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7710057","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7710057","identity":"rs-7710057","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}