Performance and Clinical Utility of Follow-Up Blood Cultures in the NICU: A 10-Year Retrospective Study

Performance and Clinical Utility of Follow-Up Blood Cultures in the NICU: A 10-Year Retrospective Study | 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 Performance and Clinical Utility of Follow-Up Blood Cultures in the NICU: A 10-Year Retrospective Study Yuka Suzuki, Daisuke Kinoshita, Takeshi Utsunomiya, Akira Nishimura This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8791133/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Persistent bacteraemia is rare in adults with gram-negative rod (GNR) infections when appropriate antimicrobial therapy is administered, and routine follow-up blood cultures (FUBCs) are not generally recommended. However, neonates in the neonatal intensive care unit (NICU) have unique immunological vulnerabilities and device-related risks that may predispose them to persistent bacteraemia. Nonetheless, evidence regarding the use of FUBCs in this population remains limited. In this study, we aimed to evaluate the performance and clinical value of FUBCs in neonates with positive blood culture results. Methods A retrospective observational study of neonates admitted to the NICU of Japanese Red Cross Kyoto Daiichi Hospital between January 2015 and March 2024 was conducted. Patients with contaminated cultures were excluded from the study. Demographic variables, causative organisms, intravascular device use, meningitis, mortality within 30 days, and steroid exposure were also obtained. FUBC was defined as a repeat culture obtained ≥ 24 h after the initial positive culture. The clinical characteristics of the FUBC-positive and FUBC-negative groups were compared. FUBC performance, positivity rates by organism, and time to culture clearance were analysed. Results Among 2,569 blood culture samples, 103 were positive, and 68 cultures from 51 patients were included after excluding contaminants. FUBCs were conducted in 61 cases (89.7%), of which 18 (29.5%) were positive for the same organism. The presence of intravascular indwelling devices was significantly associated with FUBC positivity. Among gram-positive cocci, methicillin-resistant Staphylococcus aureus showed a 100% positivity rate, while Group B Streptococcus (GBS) and early onset bacteraemia showed 0% positivity. Among the GNR, Escherichia coli showed persistent bacteraemia in all FUBC-positive cases. The median time to blood culture clearance was 5.5 days. Conclusions The FUBC positivity rate of patients in NICU was higher than that reported in adult populations. FUBCs may be valuable for infants with intravascular devices, while routine FUBCs may not be necessary for early onset or GBS bacteraemia. Further multicentre studies are required to define evidence-based NICU-specific FUBC strategies. Neonate bacteraemia follow-up blood culture neonatal intensive care unit neonatal intensive care unit Figures Figure 1 Background Sepsis is a major cause of morbidity and mortality in neonates [ 1 – 3 ]. Follow-up blood cultures (FUBCs) in many clinical settings are routinely obtained after an initial positive blood culture result to confirm the effectiveness of treatment [ 4 – 7 ]. FUBCs can help verify the clearance of bacteraemia; however, they also require additional blood sampling, which can be particularly burdensome on neonates [ 8 ]. The reported incidence of persistent bacteraemia in adult populations is relatively low (6.6–14%) [ 9 , 10 ], and FUBCs are generally recommended for only infections caused by Staphylococcus aureus or Candida [ 4 – 7 ]. Conversely, persistent bacteraemia due to a gram-negative rod (GNR) is uncommon when appropriate antimicrobial therapy is administered, and routine FUBCs are typically deemed unnecessary in these cases [ 9 – 13 ]. However, in paediatric patients under 18 years of age, the FUBC positivity rate for GNR bacteraemia has been reported to reach as high as 21%, indicating a potential clinical role [ 14 ]. The risk factors for persistent bacteraemia in children include Staphylococcus aureus , Pseudomonas aeruginosa , fungal infections, a history of bloodstream infection, and the presence of a central venous catheter. Streptococcal and anaerobic infections infrequently yield positive FUBCs [ 15 , 16 ]. Neonates, especially preterm infants in the neonatal intensive care unit (NICU), represent a distinct population with unique immunological vulnerabilities, pathogen distributions, and device-related risks that can affect the persistence of bacteraemia. However, evidence regarding the role and utility of FUBCs in the NICU remains limited. To address this gap, we conducted a retrospective single-centre study to evaluate the performance and clinical usefulness of FUBCs in neonates with bloodstream infections. Methods Study design and setting A retrospective observational study of neonates admitted to the NICU of Kyoto First Red Cross Hospital between 1 January 2015 and 31 March 2024 was conducted. All cases with at least one positive blood culture during hospitalisation were screened. Blood cultures that were considered contaminated were excluded from the analysis. Data collection Demographic and clinical variables included sex, gestational age, birth weight, postnatal age at the time of the initial positive blood culture, organism identification and antimicrobial susceptibility. Medical records were reviewed to determine the presence of intravascular indwelling devices, meningitis, and mortality within 30 days of blood culture collection, and steroid exposure within 48 h before the culture collection. Blood culture collection The puncture site was disinfected with ethanol and allowed to dry before sampling, following institutional protocols. Blood was collected from two separate sites whenever feasible, with 0.5–1.0 mL inoculated into paediatric aerobic bottles. Anaerobic bottles were added when intra-abdominal infection was suspected. Definitions FUBC was defined as a repeat blood culture collected ≥ 24 h after the initial positive culture to assess the treatment response. Persistent bacteraemia was defined as continuous growth of the same organism. Statistical analysis Demographic and clinical characteristics were compared between the FUBC-positive and FUBC-negative groups. Continuous variables were analysed using the Wilcoxon rank-sum test and are expressed as medians with interquartile ranges. Categorical variables were compared using the chi-square test. Statistical significance was set at p value of < 0.05. FUBC performance and positivity rates were summarised by organism. The number of days until blood culture clearance was also evaluated in FUBC-positive cases. Results Overall, 2,985 neonates were hospitalised, and 2,569 blood culture samples were obtained during the study period. Among these, 103 cultures were positive. After excluding contaminants, 68 positive blood cultures from 51 patients were included in the final analysis. FUBCs were conducted in 61 cases (89.7%), of which 18 (29.5%) were positive for the same organism. The median gestational age, birth weight, and postnatal age at the time of the initial positive culture between the FUBC-positive and FUBC-negative groups were similar (Table 1 , Fig. 1 ). Table 1 Patient characteristics Total (n = 61) Positive FUBC (n = 18) Negative FUBC (n = 43) p value Gestational age (weeks), median [IQR] 26 [24–29] 26.5 [24–28] 25 [24–31] 0.83 Birth weight (g), median [IQR] 772 [624–976] 750 [529–976] 892 [633–1176] 0.55 Postnatal age at positive blood culture (days), median [IQR] 24 [7–43] 24.5 [10–37] 24 [5–55] 0.77 Presence of intravascular device 49 (79%) 18 (100%) 30 (70%) < 0.01 Presence of meningitis 5 (8%) 1 (6%) 4 (9%) 0.63 Death within 30 days 6 (10%) 3 (17%) 3 (7%) 0.25 Steroid use within 48 hours prior to blood culture collection 30 (49%) 9 (50%) 21 (49%) 0.93 FUBC = follow-up blood culture The presence of intravascular indwelling devices was significantly associated with FUBC positivity (100% vs. 70% of patients). Tables 2 and 3 show the FUBC performance and positivity rates for each organism. Table 2 FUBC performance among gram-positive cocci Organism Number of isolates FUBC performed Positive FUBC Streptococcus agalactiae 10 10 (100%) 0 (0%) Methicillin-sensitive Staphylococcus aureus 7 7 (100%) 5 (71%) Methicillin-resistant Staphylococcus aureus 4 4 (100%) 4 (100%) Staphylococcus epidermidis 4 4 (100%) 2 (50%) Coagulase-negative staphylococci 3 3 (100%) 1 (33%) Staphylococcus haemolyticus 1 1 (100%) 0 (0%) Enterococcus avium 1 1 (100%) 1 (100%) Total 30 29 (96.7%) 13 (44.8%) FUBC = follow-up blood culture Table 3 FUBC performance among gram-negative bacilli Organism Number of isolates FUBC performed Positive FUBC Escherichia coli 16 16 (100%) 3 (19%) Klebsiella pneumoniae 7 5 (71%) 1 (20%) Klebsiella oxytoca 4 2 (50%) 0 (0%) Burkholderia cepacia 3 2 (67%) 1 (50%) Enterobacter cloacae 2 2 (100%) 0 (0%) Citrobacter spp. 2 2 (100%) 0 (0%) Klebsiella aerogenes 1 1 (100%) 0 (0%) Pseudomonas aeruginosa 1 0 (0%) 0 (0%) Bifidobacterium spp. 1 1 (100%) 0 (0%) Candida albicans 1 1 (100%) 0 (0%) Total 38 32 (84.2%) 5 (15.6%) FUBC = follow-up blood culture Among Gram-positive cocci, methicillin-resistant Staphylococcus aureus showed a 100% FUBC positivity rate, while Group B Streptococcus (GBS) showed a positivity rate of 0%. Among GNRs, Escherichia coli showed persistent bacteraemia in all cases with positive FUBCs. The median time to blood culture clearance among FUBC-positive cases was 5.5 days (range, 1–10 days) (Table 4 ). Table 4 Days to blood culture clearance among cases with positive FUBC Organism Days to clearance Methicillin-sensitive Staphylococcus aureus 1, 2, 3, 5, 6 Methicillin-resistant Staphylococcus aureus 3, 6, 6 Staphylococcus epidermidis 4 Coagulase-negative staphylococci 10 Enterococcus avium 6 Escherichia coli 6, 9, 10 Klebsiella pneumoniae 3 Burkholderia cepacia 3 Median (range) 5.5 (1–10) FUBC = follow-up blood culture Discussion This study is one of the few reports, nationally and internationally, that specifically evaluates the implementation status and clinical utility of FUBCs in the NICU. Unlike previous research that has focused on adults or general paediatric populations, neonates, especially preterm infants, have distinct immunological characteristics, pathogen profiles, and a significant reliance on intravascular devices. These fundamental differences necessitate an independent evaluation of the clinical significance of FUBCs in this specific population. In our NICU, the implementation rate of FUBCs was 89.7%, which is significantly higher than the rates reported in adult populations (38.9–77%). Moreover, the FUBC positivity rate was 29.5%, surpassing the adult reports of 6.6–14%, indicating that persistent bacteraemia may be more common among patients in the NICU [ 9 , 10 ]. A plausible explanation for this observation is the delayed clearance of bacteraemia that occurs due to immunological immaturity, especially among preterm infants [ 17 ]. Neonates have underdeveloped innate and adaptive immune responses compared to adults and older children. Furthermore, insufficient transplacental transfer of maternal immunoglobulin G to preterm infants may hinder bacterial clearance. Patients in the NICU are also more likely to undergo invasive procedures, including mechanical ventilation and repeated intravenous cannulation, which are established risk factors for nosocomial infection and may contribute to persistent bacteraemia [ 18 ]. The implementation rate of FUBCs for Staphylococcus aureus bacteraemia in our cohort was 100%, with a positivity rate of 81.8%. These rates are higher than those documented in adult populations, which have implementation and positivity rates of 23.1% and 44.9%, respectively [ 10 ]. These findings indicate that Staphylococcus aureus is frequently associated with persistent bacteraemia, even within the NICU setting and that FUBCs remain clinically valuable, consistent with observations in adult and older paediatric populations [ 10 , 15 ]. In cases of GNRs bacteraemia, the implementation rate of FUBCs was 84.2%, with a positivity rate of 15.6%, exceeding the rates reported in adult populations (implementation rate 25.8–69.4%, positivity rate 7.9–11.0%) [ 11 – 13 ]. Notably, all FUBC-positive Escherichia coli cases required 6, 9, and 10 days, respectively, to achieve culture negativity, indicating persistent bacteraemia in each instance. In contrast, Wiggers et al. reported a significantly low FUBC positivity rate of 1.4% for E. coli bacteraemia in adults, with persistent bacteraemia being rare [ 10 ]. Additionally, Uehara et al. demonstrated a high FUBC positivity rate of 21% among paediatric patients under 18 years of age with GNR bacteraemia, primarily treated in paediatric wards or outpatient settings, suggesting a potential role for FUBCs in paediatric populations [ 14 ]. Overall, our findings contribute to existing evidence and indicate that FUBCs may also be clinically valuable for GNR bacteraemia in the NICU. The presence of intravascular devices was significantly associated with higher FUBC positivity, aligning with previous reports [ 9 , 11 , 13 – 16 ]. Intravascular devices facilitate biofilm formation, enabling bacteraemia to persist despite appropriate antimicrobial therapy [ 19 ]. Since many patients in the NICU require prolonged device placement, this factor likely contributed substantially to the observed persistence of bacteraemia in this cohort [ 20 ]. Conversely, none of the ten cases of GBS bacteraemia showed FUBC positivity, consistent with the findings of adult and paediatric studies. Similarly, the FUBC positivity rate for early-onset bacteraemia was 0 [ 10 , 16 ]. These results show that routine FUBCs may not be necessary for GBS or early-onset bacteraemia in the NICU. The main strength of this study is its evaluation of FUBC implementation and outcomes over approximately 10 years in the NICU population. Our findings may help reduce unnecessary FUBC procedures while supporting targeted use in high-risk cases, thus facilitating appropriate antimicrobial management. This study has some limitations. First, this was a retrospective single-centre study with a limited sample size; however, the long study period likely reflects real-world NICU practice. Second, the timing of FUBCs was not standardised and depended on the attending physician’s discretion. Nevertheless, treatment decisions at our institution are discussed in daily multidisciplinary conferences, which may have minimised inter-physician variability in treatment. Finally, blood culture results were not routinely reported on weekends, potentially influencing the assessment of the postnatal age at positivity and duration of bacteraemia. The overall impact of this limitation is considered limited, since the primary outcomes were FUBC positivity and persistence of bacteraemia. Conclusion In this NICU cohort, the FUBC positivity rate was significantly higher than that observed in adult populations, indicating that FUBCs may have greater clinical value in neonates than in adults. Additionally, the strong association between intravascular indwelling devices and persistent bacteraemia further supports the selective use of FUBCs in high-risk infants. Conversely, routine FUBCs may not be necessary for early-onset or GBS bacteraemia, as the positivity rate was 0. Larger multicentre studies are essential to determine the optimal use of FUBCs in neonatal populations and establish evidence-based guidelines tailored to the unique characteristics of the NICU. Abbreviations GNR - Gram-negative rod FUBCs – Follow-up blood cultures NICU – Neonatal intensive care unit GBS - Group B Streptococcus Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the Japanese Red Cross Kyoto Daiichi Hospital (approval no. 1703). Informed consent was waived based on an opt-out approach, in accordance with the institutional guidelines and ethical standards of the Declaration of Helsinki. Consent for publication Not applicable. (Participants were informed through an opt-out public notice, and no identifiable personal information is included in this article.) Availability of data and materials Competing interests The authors declare no conflicts of interest. Funding This research did not receive any specific grants from any funding agencies in the public, commercial, or not-for-profit sectors. Author contribution Yuka Suzuki was responsible for conceptualizing the study, as well as collecting, analyzing, and interpreting the data. She also created the figure and tables and wrote the manuscript. Daisuke Kinoshita conceived the study, participated in data collection, analysis, and interpretation, and provided critical review and guidance for the manuscript's structure and writing. Takeshi Utsunomiya contributed to data collection and analysis and critically reviewed the structure of the manuscript. Akira Nishimura was involved in data collection and critically reviewed the manuscript's structure. All authors have reviewed the final version of the manuscript prior to its publication. Data Availability The datasets generated and analysed during the current study are not publicly available due to patient privacy concerns but are available from the corresponding author on reasonable request. References Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R , et al. Global incidence and mortality of neonatal sepsis: A systematic review and meta-analysis. Arch Dis Child . 2021;106:745-52. Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE , et al . Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet . 2012;379:2151-61. Attia Hussein Mahmoud H, Parekh R, Dhandibhotla S, Sai T, Pradhan A, Alugula S , et al. Insight into neonatal sepsis: an overview. Cureus . 2023;15:e45530. McMullan BJ, Campbell AJ, Blyth CC, McNeil JC, Montgomery CP, Tong SYC, et al . Clinical management of Staphylococcus aureus bacteremia in neonates, children, and adolescents. Pediatrics . 2020;146:e20200134. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L , et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis . 2016;62:e1-50. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ , et al. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis . 2011;52:e18-55. Minter DJ, Appa A, Chambers HF, Doernberg SB. Contemporary management of Staphylococcus aureus bacteremia-controversies in clinical practice. Clin Infect Dis . 2023;77:e57-68. Jung N, Kim C, Kim H, Seo Y, Hwang J, Yang M, et al. Changes to blood-sampling protocol to reduce the sampling amount in neonatal intensive care units: A quality improvement project. J Clin Med . 2023;12:5712. Canzoneri CN, Akhavan BJ, Tosur Z, Andrade PEA, Aisenberg GM. Follow-up blood cultures in Gram-negative bacteremia: Are they needed? Clin Infect Dis . 2017;65:1776-9. Wiggers JB, Xiong W, Daneman N. Sending repeat cultures: Is there a role in the management of bacteremic episodes? (SCRIBE study). BMC Infect Dis . 2016;16:286. Yildiz M, Habibi H, Altin FB, Corbacioglu SK, Ozger HS. The effect of follow-up blood cultures on mortality and antibiotic use in gram-negative bloodstream infections. BMC Infect Dis . 2023;23:564. Ong SWX, Luo J, Fridman DJ, Lee SM, Johnstone J, Schwartz KL , et al. Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: A retrospective population-wide cohort study. Clin Microbiol Infect . 2024;30:890-8. Mitaka H, Gomez T, Lee YI, Perlman DC. Risk factors for positive follow-up blood cultures in Gram-negative bacilli bacteremia: Implications for selecting who needs follow-up blood cultures. Open Forum Infect Dis . 2020;7:ofaa110. Uehara E, Shoji K, Mikami M, Ishiguro A, Miyairi I. Utility of follow-up blood cultures for Gram-negative rod bacteremia in children. J Infect Chemother . 2019;25:738-41. Cardenas-Comfort C, Kaplan SL, Vallejo JG, McNeil JC. Follow-up blood cultures in children with Staphylococcus aureus bacteremia. Pediatrics . 2020;146:e20201821. Puthawala CM, Feinn RS, Rivera-Viñas J, Lee H, Murray TS, Peaper DR. Persistent bloodstream infection in children: Examining the role for repeat blood cultures. J Clin Microbiol . 2024;62:e0099824. Melville JM, Moss TJM. The immune consequences of preterm birth. Front Neurosci . 2013;7:79. Wang L, Du KN, Zhao YL, Yu YJ, Sun L, Jiang HB. Risk factors of nosocomial infection for infants in neonatal intensive care units: A systematic review and meta-analysis. Med Sci Monit . 2019;25:8213-20. Aslam S. Effect of antibacterials on biofilms. Am J Infect Control . 2008;36:S175.e9–11. Torre FPF, Baldanzi G, Troster EJ. Risk factors for vascular catheter-related bloodstream infections in pediatric intensive care units. Rev Bras Ter Intensiva . 2018;30:436-42. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Mar, 2026 Reviews received at journal 08 Mar, 2026 Reviews received at journal 16 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers invited by journal 11 Feb, 2026 Editor invited by journal 09 Feb, 2026 Editor assigned by journal 07 Feb, 2026 Submission checks completed at journal 07 Feb, 2026 First submitted to journal 04 Feb, 2026 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. 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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-8791133","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":592418850,"identity":"6660ca7a-4f84-41bf-8500-8d6ecc78ad67","order_by":0,"name":"Yuka Suzuki","email":"","orcid":"","institution":"Japanese Red Cross Society, Kyoto Daiichi Hospital, Japan","correspondingAuthor":false,"prefix":"","firstName":"Yuka","middleName":"","lastName":"Suzuki","suffix":""},{"id":592418859,"identity":"8011b4e1-597c-4879-9663-4ba20f901810","order_by":1,"name":"Daisuke Kinoshita","email":"data:image/png;base64,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","orcid":"","institution":"Japanese Red Cross Society, Kyoto Daiichi Hospital, Japan","correspondingAuthor":true,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Kinoshita","suffix":""},{"id":592418870,"identity":"d2b88481-0ab7-4484-b98f-0845d563868f","order_by":2,"name":"Takeshi Utsunomiya","email":"","orcid":"","institution":"Japanese Red Cross Society, Kyoto Daiichi Hospital, Japan","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Utsunomiya","suffix":""},{"id":592418872,"identity":"6a15c662-2a90-442f-9082-4277efe19f21","order_by":3,"name":"Akira Nishimura","email":"","orcid":"","institution":"Japanese Red Cross Society, Kyoto Daiichi Hospital, Japan","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Nishimura","suffix":""}],"badges":[],"createdAt":"2026-02-05 01:53:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8791133/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8791133/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102862203,"identity":"a499b998-f8da-4fc6-93c9-71f3eba1524a","added_by":"auto","created_at":"2026-02-17 16:16:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34624,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient inclusion and outcome.\u003c/p\u003e\n\u003cp\u003eOverall, 2,569 blood culture samples were submitted during the study period, of which 103 were positive. After excluding 35 contaminated samples, 68 positive blood culture samples from 51 patients were included in the analysis. Among these, 61 underwent follow-up blood culture (FUBC), resulting in 18 positive and 43 negative FUBC results.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8791133/v1/d378aa9e4ff528c0d4666ce0.png"},{"id":102862205,"identity":"54b30946-7609-43f6-8910-598bab037cb9","added_by":"auto","created_at":"2026-02-17 16:16:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":660227,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8791133/v1/894f6676-c6bb-45a7-9f3a-002659f18749.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Performance and Clinical Utility of Follow-Up Blood Cultures in the NICU: A 10-Year Retrospective Study","fulltext":[{"header":"Background","content":"\u003cp\u003eSepsis is a major cause of morbidity and mortality in neonates [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Follow-up blood cultures (FUBCs) in many clinical settings are routinely obtained after an initial positive blood culture result to confirm the effectiveness of treatment [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. FUBCs can help verify the clearance of bacteraemia; however, they also require additional blood sampling, which can be particularly burdensome on neonates [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The reported incidence of persistent bacteraemia in adult populations is relatively low (6.6\u0026ndash;14%) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and FUBCs are generally recommended for only infections caused by \u003cem\u003eStaphylococcus aureus\u003c/em\u003e or \u003cem\u003eCandida\u003c/em\u003e [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Conversely, persistent bacteraemia due to a gram-negative rod (GNR) is uncommon when appropriate antimicrobial therapy is administered, and routine FUBCs are typically deemed unnecessary in these cases [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, in paediatric patients under 18 years of age, the FUBC positivity rate for GNR bacteraemia has been reported to reach as high as 21%, indicating a potential clinical role [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The risk factors for persistent bacteraemia in children include \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, fungal infections, a history of bloodstream infection, and the presence of a central venous catheter. Streptococcal and anaerobic infections infrequently yield positive FUBCs [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeonates, especially preterm infants in the neonatal intensive care unit (NICU), represent a distinct population with unique immunological vulnerabilities, pathogen distributions, and device-related risks that can affect the persistence of bacteraemia. However, evidence regarding the role and utility of FUBCs in the NICU remains limited. To address this gap, we conducted a retrospective single-centre study to evaluate the performance and clinical usefulness of FUBCs in neonates with bloodstream infections.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eA retrospective observational study of neonates admitted to the NICU of Kyoto First Red Cross Hospital between 1 January 2015 and 31 March 2024 was conducted. All cases with at least one positive blood culture during hospitalisation were screened. Blood cultures that were considered contaminated were excluded from the analysis.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eDemographic and clinical variables included sex, gestational age, birth weight, postnatal age at the time of the initial positive blood culture, organism identification and antimicrobial susceptibility. Medical records were reviewed to determine the presence of intravascular indwelling devices, meningitis, and mortality within 30 days of blood culture collection, and steroid exposure within 48 h before the culture collection.\u003c/p\u003e\n\u003ch3\u003eBlood culture collection\u003c/h3\u003e\n\u003cp\u003eThe puncture site was disinfected with ethanol and allowed to dry before sampling, following institutional protocols. Blood was collected from two separate sites whenever feasible, with 0.5\u0026ndash;1.0 mL inoculated into paediatric aerobic bottles. Anaerobic bottles were added when intra-abdominal infection was suspected.\u003c/p\u003e\n\u003ch3\u003eDefinitions\u003c/h3\u003e\n\u003cp\u003eFUBC was defined as a repeat blood culture collected\u0026thinsp;\u0026ge;\u0026thinsp;24 h after the initial positive culture to assess the treatment response. Persistent bacteraemia was defined as continuous growth of the same organism.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDemographic and clinical characteristics were compared between the FUBC-positive and FUBC-negative groups. Continuous variables were analysed using the Wilcoxon rank-sum test and are expressed as medians with interquartile ranges. Categorical variables were compared using the chi-square test. Statistical significance was set at p value of \u0026lt;\u0026thinsp;0.05. FUBC performance and positivity rates were summarised by organism. The number of days until blood culture clearance was also evaluated in FUBC-positive cases.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOverall, 2,985 neonates were hospitalised, and 2,569 blood culture samples were obtained during the study period. Among these, 103 cultures were positive. After excluding contaminants, 68 positive blood cultures from 51 patients were included in the final analysis.\u003c/p\u003e \u003cp\u003eFUBCs were conducted in 61 cases (89.7%), of which 18 (29.5%) were positive for the same organism. The median gestational age, birth weight, and postnatal age at the time of the initial positive culture between the FUBC-positive and FUBC-negative groups were similar (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\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 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics\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=\"char\" char=\".\" 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\u003eTotal (n\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive FUBC (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative FUBC (n\u0026thinsp;=\u0026thinsp;43)\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\u003eGestational age (weeks), median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 [24\u0026ndash;29]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.5 [24\u0026ndash;28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 [24\u0026ndash;31]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (g), median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e772 [624\u0026ndash;976]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e750 [529\u0026ndash;976]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e892 [633\u0026ndash;1176]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostnatal age at positive blood culture (days), median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 [7\u0026ndash;43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.5 [10\u0026ndash;37]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 [5\u0026ndash;55]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of intravascular device\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of meningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath within 30 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSteroid use within 48 hours prior to blood culture collection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eFUBC\u0026thinsp;=\u0026thinsp;follow-up blood culture\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe presence of intravascular indwelling devices was significantly associated with FUBC positivity (100% vs. 70% of patients). Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e show the FUBC performance and positivity rates for each organism.\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFUBC performance among gram-positive cocci\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrganism\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of isolates\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFUBC performed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive FUBC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus agalactiae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethicillin-sensitive \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaphylococcus epidermidis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCoagulase-negative staphylococci\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus haemolyticus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus avium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (96.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (44.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eFUBC\u0026thinsp;=\u0026thinsp;follow-up blood culture\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFUBC performance among gram-negative bacilli\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrganism\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of isolates\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFUBC performed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePositive FUBC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella oxytoca\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBurkholderia cepacia\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterobacter cloacae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCitrobacter spp.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella aerogenes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBifidobacterium spp.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (84.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eFUBC\u0026thinsp;=\u0026thinsp;follow-up blood culture\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong Gram-positive cocci, methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e showed a 100% FUBC positivity rate, while Group B Streptococcus (GBS) showed a positivity rate of 0%. Among GNRs, \u003cem\u003eEscherichia coli\u003c/em\u003e showed persistent bacteraemia in all cases with positive FUBCs.\u003c/p\u003e \u003cp\u003eThe median time to blood culture clearance among FUBC-positive cases was 5.5 days (range, 1\u0026ndash;10 days) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDays to blood culture clearance among cases with positive FUBC\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrganism\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDays to clearance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethicillin-sensitive \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1, 2, 3, 5, 6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3, 6, 6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCoagulase-negative staphylococci\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus avium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6, 9, 10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBurkholderia cepacia\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5 (1\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eFUBC\u0026thinsp;=\u0026thinsp;follow-up blood culture\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is one of the few reports, nationally and internationally, that specifically evaluates the implementation status and clinical utility of FUBCs in the NICU. Unlike previous research that has focused on adults or general paediatric populations, neonates, especially preterm infants, have distinct immunological characteristics, pathogen profiles, and a significant reliance on intravascular devices. These fundamental differences necessitate an independent evaluation of the clinical significance of FUBCs in this specific population.\u003c/p\u003e \u003cp\u003eIn our NICU, the implementation rate of FUBCs was 89.7%, which is significantly higher than the rates reported in adult populations (38.9\u0026ndash;77%). Moreover, the FUBC positivity rate was 29.5%, surpassing the adult reports of 6.6\u0026ndash;14%, indicating that persistent bacteraemia may be more common among patients in the NICU [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A plausible explanation for this observation is the delayed clearance of bacteraemia that occurs due to immunological immaturity, especially among preterm infants [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Neonates have underdeveloped innate and adaptive immune responses compared to adults and older children. Furthermore, insufficient transplacental transfer of maternal immunoglobulin G to preterm infants may hinder bacterial clearance. Patients in the NICU are also more likely to undergo invasive procedures, including mechanical ventilation and repeated intravenous cannulation, which are established risk factors for nosocomial infection and may contribute to persistent bacteraemia [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe implementation rate of FUBCs for \u003cem\u003eStaphylococcus aureus\u003c/em\u003e bacteraemia in our cohort was 100%, with a positivity rate of 81.8%. These rates are higher than those documented in adult populations, which have implementation and positivity rates of 23.1% and 44.9%, respectively [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. These findings indicate that \u003cem\u003eStaphylococcus aureus\u003c/em\u003e is frequently associated with persistent bacteraemia, even within the NICU setting and that FUBCs remain clinically valuable, consistent with observations in adult and older paediatric populations [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn cases of GNRs bacteraemia, the implementation rate of FUBCs was 84.2%, with a positivity rate of 15.6%, exceeding the rates reported in adult populations (implementation rate 25.8\u0026ndash;69.4%, positivity rate 7.9\u0026ndash;11.0%) [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Notably, all FUBC-positive \u003cem\u003eEscherichia coli\u003c/em\u003e cases required 6, 9, and 10 days, respectively, to achieve culture negativity, indicating persistent bacteraemia in each instance. In contrast, Wiggers et al. reported a significantly low FUBC positivity rate of 1.4% for \u003cem\u003eE. coli\u003c/em\u003e bacteraemia in adults, with persistent bacteraemia being rare [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Additionally, Uehara et al. demonstrated a high FUBC positivity rate of 21% among paediatric patients under 18 years of age with GNR bacteraemia, primarily treated in paediatric wards or outpatient settings, suggesting a potential role for FUBCs in paediatric populations [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Overall, our findings contribute to existing evidence and indicate that FUBCs may also be clinically valuable for GNR bacteraemia in the NICU.\u003c/p\u003e \u003cp\u003eThe presence of intravascular devices was significantly associated with higher FUBC positivity, aligning with previous reports [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Intravascular devices facilitate biofilm formation, enabling bacteraemia to persist despite appropriate antimicrobial therapy [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Since many patients in the NICU require prolonged device placement, this factor likely contributed substantially to the observed persistence of bacteraemia in this cohort [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConversely, none of the ten cases of GBS bacteraemia showed FUBC positivity, consistent with the findings of adult and paediatric studies. Similarly, the FUBC positivity rate for early-onset bacteraemia was 0 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These results show that routine FUBCs may not be necessary for GBS or early-onset bacteraemia in the NICU.\u003c/p\u003e \u003cp\u003eThe main strength of this study is its evaluation of FUBC implementation and outcomes over approximately 10 years in the NICU population. Our findings may help reduce unnecessary FUBC procedures while supporting targeted use in high-risk cases, thus facilitating appropriate antimicrobial management. This study has some limitations. First, this was a retrospective single-centre study with a limited sample size; however, the long study period likely reflects real-world NICU practice. Second, the timing of FUBCs was not standardised and depended on the attending physician\u0026rsquo;s discretion. Nevertheless, treatment decisions at our institution are discussed in daily multidisciplinary conferences, which may have minimised inter-physician variability in treatment. Finally, blood culture results were not routinely reported on weekends, potentially influencing the assessment of the postnatal age at positivity and duration of bacteraemia. The overall impact of this limitation is considered limited, since the primary outcomes were FUBC positivity and persistence of bacteraemia.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this NICU cohort, the FUBC positivity rate was significantly higher than that observed in adult populations, indicating that FUBCs may have greater clinical value in neonates than in adults. Additionally, the strong association between intravascular indwelling devices and persistent bacteraemia further supports the selective use of FUBCs in high-risk infants. Conversely, routine FUBCs may not be necessary for early-onset or GBS bacteraemia, as the positivity rate was 0.\u003c/p\u003e \u003cp\u003e Larger multicentre studies are essential to determine the optimal use of FUBCs in neonatal populations and establish evidence-based guidelines tailored to the unique characteristics of the NICU.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGNR - Gram-negative rod\u003c/p\u003e\n\u003cp\u003eFUBCs \u0026ndash; Follow-up blood cultures\u003c/p\u003e\n\u003cp\u003eNICU \u0026ndash; Neonatal intensive care unit\u003c/p\u003e\n\u003cp\u003eGBS - Group B Streptococcus\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Japanese Red Cross Kyoto Daiichi Hospital (approval no. 1703). Informed consent was waived based on an opt-out approach, in accordance with the institutional guidelines and ethical standards of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. (Participants were informed through an opt-out public notice, and no identifiable personal information is included in this article.)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grants from any funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor contribution \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuka Suzuki was responsible for conceptualizing the study, as well as collecting, analyzing, and interpreting the data. She also created the figure and tables and wrote the manuscript. Daisuke Kinoshita conceived the study, participated in data collection, analysis, and interpretation, and provided critical review and guidance for the manuscript's structure and writing. Takeshi Utsunomiya contributed to data collection and analysis and critically reviewed the structure of the manuscript. Akira Nishimura was involved in data collection and critically reviewed the manuscript's structure. All authors have reviewed the final version of the manuscript prior to its publication.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to patient privacy concerns but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R\u003cem\u003e, et al.\u003c/em\u003e Global incidence and mortality of neonatal sepsis: A systematic review and meta-analysis. Arch Dis Child\u003cem\u003e. \u003c/em\u003e2021;106:745-52.\u003c/li\u003e\n\u003cli\u003eLiu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE\u003cem\u003e, \u003c/em\u003eet\u003cem\u003e \u003c/em\u003eal\u003cem\u003e.\u003c/em\u003e Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet\u003cem\u003e. \u003c/em\u003e2012;379:2151-61.\u003c/li\u003e\n\u003cli\u003eAttia Hussein Mahmoud H, Parekh R, Dhandibhotla S, Sai T, Pradhan A, Alugula S\u003cem\u003e, \u003c/em\u003eet\u003cem\u003e \u003c/em\u003eal. Insight into neonatal sepsis: an overview. Cureus\u003cem\u003e. \u003c/em\u003e2023;15:e45530.\u003c/li\u003e\n\u003cli\u003eMcMullan BJ, Campbell AJ, Blyth CC, McNeil JC, Montgomery CP, Tong SYC, et al\u003cem\u003e.\u003c/em\u003e Clinical management of Staphylococcus aureus bacteremia in neonates, children, and adolescents. Pediatrics\u003cem\u003e. \u003c/em\u003e2020;146:e20200134.\u003c/li\u003e\n\u003cli\u003ePappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L\u003cem\u003e, \u003c/em\u003eet\u003cem\u003e \u003c/em\u003eal. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis\u003cem\u003e. \u003c/em\u003e2016;62:e1-50.\u003c/li\u003e\n\u003cli\u003eLiu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ\u003cem\u003e, \u003c/em\u003eet al. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis\u003cem\u003e. \u003c/em\u003e2011;52:e18-55.\u003c/li\u003e\n\u003cli\u003eMinter DJ, Appa A, Chambers HF, Doernberg SB. Contemporary management of Staphylococcus aureus bacteremia-controversies in clinical practice. Clin Infect Dis\u003cem\u003e. \u003c/em\u003e2023;77:e57-68.\u003c/li\u003e\n\u003cli\u003eJung N, Kim C, Kim H, Seo Y, Hwang J, Yang M, et al. Changes to blood-sampling protocol to reduce the sampling amount in neonatal intensive care units: A quality improvement project. J Clin Med\u003cem\u003e. \u003c/em\u003e2023;12:5712.\u003c/li\u003e\n\u003cli\u003eCanzoneri CN, Akhavan BJ, Tosur Z, Andrade PEA, Aisenberg GM. Follow-up blood cultures in Gram-negative bacteremia: Are they needed? Clin Infect Dis\u003cem\u003e. \u003c/em\u003e2017;65:1776-9.\u003c/li\u003e\n\u003cli\u003eWiggers JB, Xiong W, Daneman N. Sending repeat cultures: Is there a role in the management of bacteremic episodes? (SCRIBE study). BMC Infect Dis\u003cem\u003e. \u003c/em\u003e2016;16:286.\u003c/li\u003e\n\u003cli\u003eYildiz M, Habibi H, Altin FB, Corbacioglu SK, Ozger HS. The effect of follow-up blood cultures on mortality and antibiotic use in gram-negative bloodstream infections. BMC Infect Dis\u003cem\u003e. \u003c/em\u003e2023;23:564.\u003c/li\u003e\n\u003cli\u003eOng SWX, Luo J, Fridman DJ, Lee SM, Johnstone J, Schwartz KL\u003cem\u003e, \u003c/em\u003eet al. Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: A retrospective population-wide cohort study. Clin Microbiol Infect\u003cem\u003e. \u003c/em\u003e2024;30:890-8.\u003c/li\u003e\n\u003cli\u003eMitaka H, Gomez T, Lee YI, Perlman DC. Risk factors for positive follow-up blood cultures in Gram-negative bacilli bacteremia: Implications for selecting who needs follow-up blood cultures. Open Forum Infect Dis\u003cem\u003e. \u003c/em\u003e2020;7:ofaa110.\u003c/li\u003e\n\u003cli\u003eUehara E, Shoji K, Mikami M, Ishiguro A, Miyairi I. Utility of follow-up blood cultures for Gram-negative rod bacteremia in children. J Infect Chemother\u003cem\u003e. \u003c/em\u003e2019;25:738-41.\u003c/li\u003e\n\u003cli\u003eCardenas-Comfort C, Kaplan SL, Vallejo JG, McNeil JC. Follow-up blood cultures in children with Staphylococcus aureus bacteremia. Pediatrics\u003cem\u003e. \u003c/em\u003e2020;146:e20201821.\u003c/li\u003e\n\u003cli\u003ePuthawala CM, Feinn RS, Rivera-Vi\u0026ntilde;as J, Lee H, Murray TS, Peaper DR. Persistent bloodstream infection in children: Examining the role for repeat blood cultures. J Clin Microbiol\u003cem\u003e. \u003c/em\u003e2024;62:e0099824.\u003c/li\u003e\n\u003cli\u003eMelville JM, Moss TJM. The immune consequences of preterm birth. Front Neurosci\u003cem\u003e. \u003c/em\u003e2013;7:79.\u003c/li\u003e\n\u003cli\u003eWang L, Du KN, Zhao YL, Yu YJ, Sun L, Jiang HB. Risk factors of nosocomial infection for infants in neonatal intensive care units: A systematic review and meta-analysis. Med Sci Monit\u003cem\u003e. \u003c/em\u003e2019;25:8213-20.\u003c/li\u003e\n\u003cli\u003eAslam S. Effect of antibacterials on biofilms. Am J Infect Control\u003cem\u003e. \u003c/em\u003e2008;36:S175.e9\u0026ndash;11.\u003c/li\u003e\n\u003cli\u003eTorre FPF, Baldanzi G, Troster EJ. Risk factors for vascular catheter-related bloodstream infections in pediatric intensive care units. Rev Bras Ter Intensiva\u003cem\u003e. \u003c/em\u003e2018;30:436-42.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neonate, bacteraemia, follow-up blood culture, neonatal intensive care unit, neonatal intensive care unit","lastPublishedDoi":"10.21203/rs.3.rs-8791133/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8791133/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePersistent bacteraemia is rare in adults with gram-negative rod (GNR) infections when appropriate antimicrobial therapy is administered, and routine follow-up blood cultures (FUBCs) are not generally recommended. However, neonates in the neonatal intensive care unit (NICU) have unique immunological vulnerabilities and device-related risks that may predispose them to persistent bacteraemia. Nonetheless, evidence regarding the use of FUBCs in this population remains limited. In this study, we aimed to evaluate the performance and clinical value of FUBCs in neonates with positive blood culture results.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective observational study of neonates admitted to the NICU of Japanese Red Cross Kyoto Daiichi Hospital between January 2015 and March 2024 was conducted. Patients with contaminated cultures were excluded from the study. Demographic variables, causative organisms, intravascular device use, meningitis, mortality within 30 days, and steroid exposure were also obtained. FUBC was defined as a repeat culture obtained\u0026thinsp;\u0026ge;\u0026thinsp;24 h after the initial positive culture. The clinical characteristics of the FUBC-positive and FUBC-negative groups were compared. FUBC performance, positivity rates by organism, and time to culture clearance were analysed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 2,569 blood culture samples, 103 were positive, and 68 cultures from 51 patients were included after excluding contaminants. FUBCs were conducted in 61 cases (89.7%), of which 18 (29.5%) were positive for the same organism. The presence of intravascular indwelling devices was significantly associated with FUBC positivity. Among gram-positive cocci, methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e showed a 100% positivity rate, while Group B Streptococcus (GBS) and early onset bacteraemia showed 0% positivity. Among the GNR, \u003cem\u003eEscherichia coli\u003c/em\u003e showed persistent bacteraemia in all FUBC-positive cases. The median time to blood culture clearance was 5.5 days.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe FUBC positivity rate of patients in NICU was higher than that reported in adult populations. FUBCs may be valuable for infants with intravascular devices, while routine FUBCs may not be necessary for early onset or GBS bacteraemia. Further multicentre studies are required to define evidence-based NICU-specific FUBC strategies.\u003c/p\u003e","manuscriptTitle":"Performance and Clinical Utility of Follow-Up Blood Cultures in the NICU: A 10-Year Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-17 16:15:54","doi":"10.21203/rs.3.rs-8791133/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-09T07:55:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-08T19:01:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-16T23:26:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"114140657518487086020321010916201944899","date":"2026-02-14T04:30:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"237243298142582841385396511024097015129","date":"2026-02-12T01:35:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-12T01:31:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-09T07:18:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-07T14:07:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-07T14:05:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-02-05T01:35:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"584eeb11-365d-45bd-9c63-2f0d719eeea4","owner":[],"postedDate":"February 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-02T04:09:43+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-17 16:15:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8791133","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8791133","identity":"rs-8791133","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}