Neonatal Fever in the Emergency Department A Retrospective Study

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SMEESTER, Inge ROGGEN This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6844796/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Oct, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted 4 You are reading this latest preprint version Abstract Purpose: This study aimed to assess the epidemiology and diagnosis of severe bacterial infections in febrile neonates brought to the emergency department. Methods: We conducted a retrospective review of medical records from neonates aged 28 days or younger admitted for fever to the emergency department of a Belgian tertiary hospital between January 2020 and December 2022. Results: Among 190 febrile neonates, 17 (9%) were diagnosed with a severe bacterial infection. Most were urinary tract infections (15 cases), mainly caused by Escherichia coli . Four neonates (2%) had invasive bacterial infections: one Pseudomonas aeruginosa meningitis, one Staphylococcus aureus bloodstream infection, and two urinary tract infections with concomitant bacteremia. Twelve of the 17 pathogens (71%) showed resistance to at least one antibiotic. Three neonates with severe bacterial infections, including two with invasive disease, had a CRP level below 10 mg/L at admission. Male neonates were at higher risk of bacterial infection. Conclusion: Severe bacterial infections were less frequent than expected, with Escherichia coli urinary tract infections predominating. CRP was not a reliable marker for invasive disease. These findings support a targeted and individualized approach to antibiotic use and suggest that, in neonates older than 21 days with reassuring initial evaluation, close follow-up may be considered over systematic lumbar puncture. Febrile neonate severe bacterial infection invasive bacterial infection antibiotic resistance C-reactive protein INTRODUCTION Neonatal infection occurs from birth until the 28th day of life ( 1 , 2 ). The first sign is often pyrexia, which is defined in neonates as a rectal temperature of 38°C or above ( 3 – 5 ). Newborns are especially susceptible to infections due to their underdeveloped immunity, immature physical barriers, and nascent microbiota critical for immune defense ( 6 ). As they age, the risk of severe bacterial infections (SBI) decreases, with febrile neonates facing twice the risk of bacteremia or meningitis compared to infants in their second month of life ( 7 ). Despite a decline in neonatal infections, SBI still result in high mortality rates. In 2022, newborns comprised 47% of the 4.9 million child deaths under five ( 8 ). Sepsis, meningitis and pneumoniae contribute to 16% of neonatal mortality ( 9 ). Notwithstanding the complexity of assessing SBI risk in febrile neonates due to nonspecific symptoms and unreliable biomarkers after the initial peak of fever ( 10 – 15 ), SBI must be ruled out in febrile neonates aged < 28 days, as delayed diagnosis heightens morbidity and mortality. At Queen Fabiola University Children's Hospital (HUDERF), following a protocol, blood, urine, and cerebrospinal fluid samples are systematically collected for bacterial culture, cytological and biochemical analysis, and meningitis panel polymerase chain reaction on cerebrospinal fluid, prior to starting intravenous treatment with cefotaxime and amoxicillin ( 16 ). Although caution is warranted, antibiotics induce bacterial resistance, disrupt microbiota, and have documented consequences for long-term health ( 17 – 20 ). Interestingly, few hospitalized febrile neonates on broad-spectrum antibiotics have an SBI, questioning the necessity of our maximalist invasive approach ( 21 ). MATERIALS AND METHODS Study Design, Setting and Population This retrospective study reviewed medical records of neonates aged ≤ 28 days admitted to the emergency department of a tertiary Belgian hospital for fever between January 1, 2020, and December 31, 2022. Inclusion criteria included neonates aged ≤ 28 days with a rectal temperature ≥ 38°C, recorded at home or upon admission. Definitions We defined severe bacterial infection as bacteremia, meningitis, or urinary tract infection (UTI) with clinical signs of infection. UTI is characterized by a positive urine culture with a single bacterial pathogen isolated through: Catheterization: ≥50,000 CFU/mL, ≥ 10,000 CFU/mL with pyuria, or ≥ 1,000 CFU/mL if a concurrent bag specimen shows ≥ 50,000 CFU/mL of the same pathogen with pyuria. Clean catch : ≥100,000 CFU/mL, pyuria, and at least trace nitrites or leukocyte esterase. Pyuria is defined as > 10 leukocytes/mL ( 22 , 23 ). Invasive bacterial infection includes bacteremia and bacterial meningitis. Bacteremia is defined as the isolation of a pathogenic bacterium from blood cultures. Commensals such as Staphylococcus epidermidis , Staphylococcus hominis , and Staphylococcus aureus are considered contaminants unless isolated from two or more cultures and treated as pathogens. Similarly, organisms like Streptococcus vestibularis , Streptococcus mitis , Streptococcus oralis , and gram-positive bacilli are considered contaminants unless they meet the same criteria. Bacterial meningitis refers to the isolation of a pathogenic bacterium from cerebrospinal fluid by culture, accompanied by clinical signs such as irritability. Urosepsis is diagnosed when the same pathogen is detected in both urine and blood, indicating a systemic infection originating from the urinary tract. Non-severe bacterial infections include localized infections such as abscesses, cellulitis, mastitis, and pneumonia (defined by chest radiograph). These are not associated with bacteremia. Bacterial identification was performed using MALDI-TOF spectrometry (Bruker), and antibiotic susceptibility testing was conducted with the Vitek 2 system (bioMérieux), except for Pseudomonas aeruginosa , tested by agar diffusion. Extended-spectrum beta-lactamase-producing strains were detected using disk diffusion testing followed by confirmation. RESULTS During the study period, 190 febrile neonates were admitted to the emergency department. As shown in Table 1 , 110 were male, and the mean age was 19.3 days. All 190 neonates underwent biochemical, cytological, and bacterial culture analyses of blood and urine. Lumbar puncture was performed in 187 cases; it was not conducted in three due to respiratory instability in two patients and parental refusal in one. Overall, 17 (9%) of the 190 neonates had SBI. As detailed in Table 2 , 15 (8%) were diagnosed with UTI, representing 88% of SBI cases. Urine was collected by catheterization in 13 of these 15 cases, while two were diagnosed via clean catch. All 15 neonates with UTI exhibited pyuria. Table 1 Demographic and clinical characteristics of the population All (% of all) With SBI (% of the patients with SBI) Number of patients 190 (100%) 17 (100%) Male gender 110/190 (58%) 14/17 (82%) Mean patient age 19,3 days 18,7 days Fever in the emergency department 85/190 (45%) 13/17 (76%) Fever amplitude > 38.5°C 61 (32%) 12 (71%) Prevalence of Reported Signs and Symptoms in the Sample Nasal congestion or rhinorrhea 104 (55%) 3 (18%) Cough 63 (33%) 1 (6%) Irritability 63 (33%) 9 (53%) Eating difficulties 57 (30%) 4 (24%) Dyspnea/ breathing difficulties 28 (15%) 1 (6%) Abdominal incomfort 25 (13%) 2 (12%) Nausea / Vomiting 24 (13%) 2 (12%) Fatigue 23 (12%) 1 (6%) Diarrhoea 17 (9%) 1 (6%) Apnea 3 (2%) 0 Rash 2 (1%) 0 Table 2 SBI Among the Febrile Neonates (N = 190) Urinary tract infections 15 (8%) Urosepsis 2 (1%) Bacterial meningitis 1 (0,5%) Deaths 0 Total SBI cases 17 (9%) Pathogens responsible of the 17 cases of SBI : Escherichia coli 14 (76%) Klebsiella pneumoniae 1 (6%) Staphylococcus aureus 1 (6%) Pseudomonas aeruginosa 1 (6%) Four neonates had bacteremia, including two with urosepsis. The remaining cases included: 1. Staphylococcus aureus bacteremia associated with myositis and a piriformis abscess; and 2. bacterial meningitis caused by Pseudomonas aeruginosa , originating from an orbital infection, with the pathogen also found in blood. This case involved a 20-day-old infant with a previously unknown MyD88 mutation-related immune deficiency. Escherichia coli was responsible for 93% (14/15) of UTIs, while Klebsiella pneumoniae accounted for 7% (1/15). Eleven (73%) of the 15 UTI pathogens were resistant to ampicillin, nine (60%) to amoxicillin/clavulanic acid, five (33%) to trimethoprim-sulfamethoxazole, and one (7%) to piperacillin-tazobactam. One UTI was caused by extended-spectrum β-lactamase-producing Escherichia coli. Only 21% (3/15) of UTI cases were caused by multi-susceptible Escherichia coli. Table 1 presents data showing that only 1.6% (1/63) of febrile newborns with cough and 3% (3/104) of those with nasal congestion or rhinorrhea had a SBI. Fever amplitude was specified for 186 of the 190 febrile neonates, excluding 4 patients from the fever amplitude calculations. None of the 4 had a SBI. A body temperature exceeding 38.5°C increased the risk of SBI fivefold, rising from 4–20%. Specifically, 12 of the 61 neonates with fever > 38.5°C (20%) had an SBI, compared to 5 of the 129 neonates with fever ≤ 38.5°C (4%). The mean fever was 38,8°C for the SBI group (N = 17), slightly higher than that of all neonates (38,5°C, N = 190). Among 85 neonates with documented fever in the emergency department, 13 (15%) had a SBI, compared to 4 (5%) of 105 neonates without fever in the emergency department. Contagion was documented in 5 (29%) of the 17 neonates with SBI, versus 97 (56%) of 173 neonates without SBI. As shown in Table 3 , 29.4% (5/17) of neonates with SBI had CRP levels ≤ 20 mg/L, while 47.1% (8/17) had CRP ≥ 50 mg/L. In the non-SBI group, 92.5% (160/173) had CRP ≤ 20 mg/L, whereas only 1.7% (3/173) had CRP ≥ 50 mg/L. Among the latter, two presented with pneumopathy and appendicular abscess. In the studied cohort, when CRP exceeded 25 mg/L, febrile neonates were more likely to have a severe bacterial infection than alternative diagnoses, independent of other factors. Table 3 CRP amongst febrile neonates CRP (mg/L) With SBI, n = 17 (% of SBI) Without SBI, n = 173 (% of the patients with SBI) ≤ 20 5 (29,4%) 160 (92,5%) 20 < 50 4 (23,5%) 10 (5,8%) ≥ 50 8 (47,1%) 3 (1,7%) Notably, among the three febrile neonates with SBI and CRP < 10 mg/L, two had IBI other than urosepsis: one with Pseudomonas aeruginosa meningitis in an immunocompromised neonate, and one with Staphylococcus aureus bacteremia. The cohort was predominantly male, comprising 58% (110/190) of the sample. Male newborns had a bacterial infection risk 4.1 times higher than females. The risk of severe bacterial infection in males was 12.7% (14/110), compared to 3.8% (3/80) in females. This was evident in both UTIs and IBIs, with 80% (12/15) of UTI cases and 75% (3/4) of IBI cases occurring in boys. The difference was less pronounced among newborns without severe bacterial infection, where 55% were male. In our sample, 13 (76%) of the 17 febrile neonates with SBI were ≤ 21 days old at admission. Additionally, 100% (n = 4) of the IBI cases were in this age group. No perinatal SBI were observed in neonates ≤ 7 days, though the sample size was small. The prevalence of SBI decreased with age. These findings are summarized in Table 4 . The four febrile neonates with SBI > 21 days had a UTI, all with pyuria. Table 4 Prevalence of Severe Bacterial Infection by Age Group (N = 190) Age group (days) Number of neonates Number with severe bacterial infection (% within age groupe) 0 to 7 days 7 0 (0%) 8 to 14 days 36 4 (11.1%) 15 to 21 days 67 9 (13.4%) 22 to 28 days 80 4 (5%) Total 190 17 (9%) For febrile neonates without SBI, routine nasopharyngeal swabs and cerebrospinal fluid analyses identify viruses in most cases. DISCUSSION SBI affected 9% (n = 17) of the 190 febrile neonates studied, which is below the 11–25% range reported in the literature ( 21 , 24 , 25 ). Consistent with data from published studies, the majority were Escherichia coli UTIs and affected boys. The prevalence of urinary tract infections in the sample (15/190, 8%) corresponds to the lower limit of the 10–15% range indicated in larger studies of febrile neonates in the emergency department. ( 21 , 27 ) The 13% (2/15) of urosepsis cases among UTIs exceeded the 1,5 to 4% observed in a larger series ( 27 , 28 ). Symptoms such as cough, nasal congestion, and rhinorrhea where associated with a lower risk of SBI. However, caution is warranted for male newborns without these symptoms or with a fever above 38.5°C, or when fever is observed in the emergency department. Given the prevalence of severe bacterial infections and the nonspecific nature of clinical signs, management should not rely solely on clinical evaluations. In our study, CRP had limited sensitivity for detecting SBI. Among febrile neonates with SBI, five of 17 had CRP levels below 20 mg/L, and two of four IBI cases had CRP levels below 10 mg/L, including one immunocompromised newborn. The retrospective nature of the study prevented inclusion of the time between fever onset and emergency department admission in this analysis. Although Procalcitonin has been shown to be superior in diagnosing severe bacterial infections, especially meningitis and bacteremia, CRP remains the best biomarker when Procalcitonin is not routinely available. ( 13 , 29 , 30 ) Notably, urine analyses reliably identified SBI, particularly UTIs. As highlighted in the literature, UTIs were more prevalent in males (11%) than in females (3.7%) among newborns ( 27 ). It is crucial to consider that underlying conditions may be present but undiagnosed, especially in neonates. Notably, the only case of bacterial meningitis during this retrospective period involved a child in whom an undiagnosed innate immune deficiency due to a MyD88 mutation was discovered. This mutation, which encodes a protein essential for immune signaling, has been reported in 24 cases to date ( 31 ). In addition to potential undiagnosed underlying conditions, antibiotic resistance is another critical factor. The high prevalence of ampicillin-resistant bacteria (64% in SBI and 73% in UTIs) is likely attributable to widespread intrapartum penicillin use to prevent Streptococcus agalactiae infection in university hospitals in Brussels and globally ( 24 , 32 – 35 ). Is Amoxicilline Still Indicated? During the retrospective period, no cases of Listeria monocytogenes or Enterococcus infections were detected among febrile neonates. The literature suggests a declining prevalence ( 13 , 14 , 27 , 36 ). Despite this trend, Belgian University Hospitals continue to follow empirical dual therapy with ampicillin and cefotaxime, other European centers recommend cefotaxime and an aminoglycoside pending culture results. Given the single-center, retrospective design of this study, adopting a similar strategy during the study period could have been justifiable, though caution is needed when interpreting these results. Aminoglycosides' rapid bactericidal action and renal elimination help limit the selection of resistant mutants, while once-daily dosing offers an advantage. However, caution is required due to potential renal and auditory toxicity. Lowering the Age for Routine Lumbar Puncture to 21 Days: A Possibility? The data from Martinez et al. suggest that an automatic lumbar puncture is not required in febrile neonates over 21 days of age who appear healthy and have a negative infectious work-up. However, it remains strongly recommended for febrile neonates under 21 days of age ( 37 ). This approach was validated in a prospective multicenter study by Gomez et al., in which procalcitonin was used as a marker of infection ( 38 ). The findings from our retrospective study suggest that performing lumbar puncture and administering empirical antibiotic therapy exclusively to febrile neonates ≤ 21 days would have been a reasonable strategy, which, over the 3-year study period, would not have put our patients at greater risk. No IBI cases were observed in the ≤ 21-day age group. The four cases of SBI in neonates older than 21 days were UTIs with pyuria and would, therefore, have been managed without lumbar puncture and treated empirically. This approach could reduce iatrogenic complications, procedural pain, dosing errors, and unnecessary treatments resulting from false positives. One factor not analyzed in this study is the psychosocial impact of hospitalizing febrile neonates, which can be costly, generate considerable anxiety for parents, and disrupt breastfeeding ( 39 – 42 ). Several potential biases must be acknowledged in this study. First, the exclusive selection of neonates admitted to the emergency department of HUDERF for fever could introduce selection bias, excluding other cases. Additionally, the retrospective nature of the study may have introduced recall bias due to potentially incomplete or inaccurate medical records. Data collection could also introduce information bias that might affect the quality of the data. Finally, the results from a single institution may not be generalizable to other settings. Awareness of these biases is crucial for the accurate interpretation of the results. CONCLUSION In summary, SBIs were less common in the studied febrile neonates than previously reported, with Escherichia coli UTIs identified as the predominant cause. Greater vigilance is needed for male febrile neonates without cough or rhinorrhea However, clinical management should not rely solely on these factors. CRP is a useful biomarker, but its sensitivity for the early detection of severe bacterial infections is limited. High ampicillin resistance was observed, possibly because of intrapartum prophylaxis. Considering the option of clinical re-evaluation without lumbar puncture in febrile neonates with negative work-up and older than 21 days old is probably interesting. Abbreviations CFU/mL Colony-Forming Units per Milliliter CRP C-Reactive Protein ED Emergency Department ESBL Extended-Spectrum Beta-Lactamase HUDERF Hôpital Universitaire des Enfants Reine Fabiola IBI Invasive Bacterial Infection PCR Polymerase Chain Reaction SBI Severe Bacterial Infection UTI Urinary Tract Infection Declarations From the * Emergency Department, Queen Fabiola Pediatric University Hospital, Université Libre de Bruxelles, Brussels, Belgium; † Department of Pediatrics, Infectious Disease Unit, Brussels University Hospital, Academic Children Hospital Queen Fabiola, Université Libre de Bruxelles, Brussels, Belgium; ‡ Molecular Bacteriology Laboratory, European Plotkin Institute for Vaccinology, Université Libre de Bruxelles, Brussels, Belgium; The authors have declared that no competing interests exist. This study did not receive any funding. All pertinent data are available in both the paper and its accompanying Supporting Information files. Author Contributions: SJ provided the initial idea for the project and assisted in data analysis. IR assisted in data collection. IR, SJ, and PS reviewed the manuscript. Correspondence to: [email protected] Ethics approval Ethical approval was obtained from the HUDERF Ethics Committee (reference 01/23), in accordance with the principles of the Declaration of Helsinki. Competing interests and Funding The authors have declared that no competing interests exist. This study did not receive any funding. Data Availability The data that support the findings of this study are available from Jules Lagrou ( [email protected] ) upon reasonable request. References Gomella T, Eyal F, Bany-Mohammed F (2020) Gomella’s Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs. 8e éd. McGraw-Hill Education, New York Newborn health [Internet] [cited 2024 Nov 15]. 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Cite Share Download PDF Status: Published Journal Publication published 11 Oct, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 18 Jun, 2025 Editor assigned by journal 16 Jun, 2025 Submission checks completed at journal 16 Jun, 2025 First submitted to journal 07 Jun, 2025 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-6844796","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":473079323,"identity":"30ad913b-1183-4279-bf03-b1c07e052bd6","order_by":0,"name":"Jules LAGROU","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYBACxgbmBiBlAeF9AGI2doJaGEFaJCCcGSAtzETYA9fCzAMmCWhgnpHY+PAHg4S8fPThY9I2v7bJ8zEzMH74mIPHjhmJzcY8DBKGG8+lpUnn9t02bGNmYJacuQ2vljZpoMMYN/bwmEnn9txmBGphY+bFr6X9J9Bh9mAtlj237YnR0sYAdFjifB6gFoYftxMJa+l52CzNYyCRvIGHLdmyt+F2chszYzNevxi2Jx/8+KPCxnZ+D/PBGz/+3Lad39588MNHfFoaQKQBEB0A2dkGtrkBt3ogkIczwOr+4FU8CkbBKBgFIxQAAAjpSb+T6nWYAAAAAElFTkSuQmCC","orcid":"","institution":"Queen Fabiola Children's University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jules","middleName":"","lastName":"LAGROU","suffix":""},{"id":473079324,"identity":"38a7a01a-ea25-4698-8abd-531c5f3783ba","order_by":1,"name":"Sarah JOURDAIN","email":"","orcid":"","institution":"Queen Fabiola Children's University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"JOURDAIN","suffix":""},{"id":473079325,"identity":"fe8ab4e8-3ea7-4b47-9df1-a3803c48aba4","order_by":2,"name":"Pierre R. SMEESTER","email":"","orcid":"","institution":"Queen Fabiola Children's University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pierre","middleName":"R.","lastName":"SMEESTER","suffix":""},{"id":473079326,"identity":"51bf4b22-100d-41de-a563-0d53ced079c2","order_by":3,"name":"Inge ROGGEN","email":"","orcid":"","institution":"Queen Fabiola Children's University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Inge","middleName":"","lastName":"ROGGEN","suffix":""}],"badges":[],"createdAt":"2025-06-07 22:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6844796/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6844796/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-025-06527-5","type":"published","date":"2025-10-11T15:58:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":93420026,"identity":"c115849c-8e27-4a95-b617-144cef852f94","added_by":"auto","created_at":"2025-10-13 16:09:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":589396,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6844796/v1/964809cc-e69d-4382-80ce-11f11e4968ea.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neonatal Fever in the Emergency Department A Retrospective Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eNeonatal infection occurs from birth until the 28th day of life (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The first sign is often pyrexia, which is defined in neonates as a rectal temperature of 38\u0026deg;C or above (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Newborns are especially susceptible to infections due to their underdeveloped immunity, immature physical barriers, and nascent microbiota critical for immune defense (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). As they age, the risk of severe bacterial infections (SBI) decreases, with febrile neonates facing twice the risk of bacteremia or meningitis compared to infants in their second month of life (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite a decline in neonatal infections, SBI still result in high mortality rates. In 2022, newborns comprised 47% of the 4.9\u0026nbsp;million child deaths under five (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Sepsis, meningitis and pneumoniae contribute to 16% of neonatal mortality (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Notwithstanding the complexity of assessing SBI risk in febrile neonates due to nonspecific symptoms and unreliable biomarkers after the initial peak of fever (\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), SBI must be ruled out in febrile neonates aged\u0026thinsp;\u0026lt;\u0026thinsp;28 days, as delayed diagnosis heightens morbidity and mortality. At Queen Fabiola University Children's Hospital (HUDERF), following a protocol, blood, urine, and cerebrospinal fluid samples are systematically collected for bacterial culture, cytological and biochemical analysis, and meningitis panel polymerase chain reaction on cerebrospinal fluid, prior to starting intravenous treatment with cefotaxime and amoxicillin (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough caution is warranted, antibiotics induce bacterial resistance, disrupt microbiota, and have documented consequences for long-term health (\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Interestingly, few hospitalized febrile neonates on broad-spectrum antibiotics have an SBI, questioning the necessity of our maximalist invasive approach (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e \u003cb\u003eStudy Design, Setting and Population\u003c/b\u003e \u003c/p\u003e \u003cp\u003e This retrospective study reviewed medical records of neonates aged\u0026thinsp;\u0026le;\u0026thinsp;28 days admitted to the emergency department of a tertiary Belgian hospital for fever between January 1, 2020, and December 31, 2022. Inclusion criteria included neonates aged\u0026thinsp;\u0026le;\u0026thinsp;28 days with a rectal temperature\u0026thinsp;\u0026ge;\u0026thinsp;38\u0026deg;C, recorded at home or upon admission.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDefinitions\u003c/strong\u003e \u003cp\u003eWe defined severe bacterial infection as bacteremia, meningitis, or urinary tract infection (UTI) with clinical signs of infection.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eUTI is characterized by a positive urine culture with a single bacterial pathogen isolated through:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eCatheterization: \u0026ge;50,000 CFU/mL, \u0026ge;\u0026thinsp;10,000 CFU/mL with pyuria, or \u0026ge;\u0026thinsp;1,000 CFU/mL if a concurrent bag specimen shows\u0026thinsp;\u0026ge;\u0026thinsp;50,000 CFU/mL of the same pathogen with pyuria.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eClean catch : \u0026ge;100,000 CFU/mL, pyuria, and at least trace nitrites or leukocyte esterase.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003ePyuria is defined as \u0026gt;\u0026thinsp;10 leukocytes/mL (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eInvasive bacterial infection includes bacteremia and bacterial meningitis.\u003c/p\u003e \u003cp\u003eBacteremia is defined as the isolation of a pathogenic bacterium from blood cultures. Commensals such as \u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e, \u003cem\u003eStaphylococcus hominis\u003c/em\u003e, and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e are considered contaminants unless isolated from two or more cultures and treated as pathogens. Similarly, organisms like \u003cem\u003eStreptococcus vestibularis\u003c/em\u003e, \u003cem\u003eStreptococcus mitis\u003c/em\u003e, \u003cem\u003eStreptococcus oralis\u003c/em\u003e, and gram-positive bacilli are considered contaminants unless they meet the same criteria.\u003c/p\u003e \u003cp\u003eBacterial meningitis refers to the isolation of a pathogenic bacterium from cerebrospinal fluid by culture, accompanied by clinical signs such as irritability.\u003c/p\u003e \u003cp\u003eUrosepsis is diagnosed when the same pathogen is detected in both urine and blood, indicating a systemic infection originating from the urinary tract.\u003c/p\u003e \u003cp\u003eNon-severe bacterial infections include localized infections such as abscesses, cellulitis, mastitis, and pneumonia (defined by chest radiograph). These are not associated with bacteremia.\u003c/p\u003e \u003cp\u003eBacterial identification was performed using MALDI-TOF spectrometry (Bruker), and antibiotic susceptibility testing was conducted with the Vitek 2 system (bioM\u0026eacute;rieux), except for \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, tested by agar diffusion. Extended-spectrum beta-lactamase-producing strains were detected using disk diffusion testing followed by confirmation.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eDuring the study period, 190 febrile neonates were admitted to the emergency department. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, 110 were male, and the mean age was 19.3 days. All 190 neonates underwent biochemical, cytological, and bacterial culture analyses of blood and urine. Lumbar puncture was performed in 187 cases; it was not conducted in three due to respiratory instability in two patients and parental refusal in one.\u003c/p\u003e \u003cp\u003eOverall, 17 (9%) of the 190 neonates had SBI. As detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, 15 (8%) were diagnosed with UTI, representing 88% of SBI cases. Urine was collected by catheterization in 13 of these 15 cases, while two were diagnosed via clean catch. All 15 neonates with UTI exhibited pyuria.\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\u003eDemographic and clinical characteristics of the population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll (% of all)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith SBI (% of the patients with SBI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale gender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110/190 (58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/17 (82%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean patient age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19,3 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18,7 days\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever in the emergency department\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85/190 (45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13/17 (76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever amplitude\u0026thinsp;\u0026gt;\u0026thinsp;38.5\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrevalence of Reported Signs and Symptoms in the Sample\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal congestion or rhinorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrritability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (53%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEating difficulties\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspnea/ breathing difficulties\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal incomfort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea / Vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhoea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApnea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRash\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSBI Among the Febrile Neonates (N\u0026thinsp;=\u0026thinsp;190)\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\u003eUrinary tract infections\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (8%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrosepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial meningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0,5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeaths\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal SBI cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePathogens responsible of the 17 cases of SBI\u003c/span\u003e:\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEscherichia coli\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKlebsiella pneumoniae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaphylococcus aureus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePseudomonas aeruginosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFour neonates had bacteremia, including two with urosepsis. The remaining cases included: 1. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e bacteremia associated with myositis and a piriformis abscess; and 2. bacterial meningitis caused by \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, originating from an orbital infection, with the pathogen also found in blood. This case involved a 20-day-old infant with a previously unknown MyD88 mutation-related immune deficiency.\u003c/p\u003e \u003cp\u003e \u003cem\u003eEscherichia coli\u003c/em\u003e was responsible for 93% (14/15) of UTIs, while \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e accounted for 7% (1/15).\u003c/p\u003e \u003cp\u003eEleven (73%) of the 15 UTI pathogens were resistant to ampicillin, nine (60%) to amoxicillin/clavulanic acid, five (33%) to trimethoprim-sulfamethoxazole, and one (7%) to piperacillin-tazobactam. One UTI was caused by extended-spectrum β-lactamase-producing Escherichia coli. Only 21% (3/15) of UTI cases were caused by multi-susceptible Escherichia coli.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents data showing that only 1.6% (1/63) of febrile newborns with cough and 3% (3/104) of those with nasal congestion or rhinorrhea had a SBI.\u003c/p\u003e \u003cp\u003eFever amplitude was specified for 186 of the 190 febrile neonates, excluding 4 patients from the fever amplitude calculations. None of the 4 had a SBI. A body temperature exceeding 38.5\u0026deg;C increased the risk of SBI fivefold, rising from 4\u0026ndash;20%. Specifically, 12 of the 61 neonates with fever\u0026thinsp;\u0026gt;\u0026thinsp;38.5\u0026deg;C (20%) had an SBI, compared to 5 of the 129 neonates with fever\u0026thinsp;\u0026le;\u0026thinsp;38.5\u0026deg;C (4%).\u003c/p\u003e \u003cp\u003eThe mean fever was 38,8\u0026deg;C for the SBI group (N\u0026thinsp;=\u0026thinsp;17), slightly higher than that of all neonates (38,5\u0026deg;C, N\u0026thinsp;=\u0026thinsp;190). Among 85 neonates with documented fever in the emergency department, 13 (15%) had a SBI, compared to 4 (5%) of 105 neonates without fever in the emergency department. Contagion was documented in 5 (29%) of the 17 neonates with SBI, versus 97 (56%) of 173 neonates without SBI.\u003c/p\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, 29.4% (5/17) of neonates with SBI had CRP levels\u0026thinsp;\u0026le;\u0026thinsp;20 mg/L, while 47.1% (8/17) had CRP\u0026thinsp;\u0026ge;\u0026thinsp;50 mg/L. In the non-SBI group, 92.5% (160/173) had CRP\u0026thinsp;\u0026le;\u0026thinsp;20 mg/L, whereas only 1.7% (3/173) had CRP\u0026thinsp;\u0026ge;\u0026thinsp;50 mg/L. Among the latter, two presented with pneumopathy and appendicular abscess. In the studied cohort, when CRP exceeded 25 mg/L, febrile neonates were more likely to have a severe bacterial infection than alternative diagnoses, independent of other factors.\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\u003eCRP amongst febrile neonates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith SBI, n\u0026thinsp;=\u0026thinsp;17 (% of SBI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWithout SBI, n\u0026thinsp;=\u0026thinsp;173 (% of the patients with SBI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (29,4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e160 (92,5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026thinsp;\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (23,5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (5,8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (47,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1,7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNotably, among the three febrile neonates with SBI and CRP\u0026thinsp;\u0026lt;\u0026thinsp;10 mg/L, two had IBI other than urosepsis: one with \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e meningitis in an immunocompromised neonate, and one with \u003cem\u003eStaphylococcus aureus\u003c/em\u003e bacteremia.\u003c/p\u003e \u003cp\u003eThe cohort was predominantly male, comprising 58% (110/190) of the sample. Male newborns had a bacterial infection risk 4.1 times higher than females. The risk of severe bacterial infection in males was 12.7% (14/110), compared to 3.8% (3/80) in females. This was evident in both UTIs and IBIs, with 80% (12/15) of UTI cases and 75% (3/4) of IBI cases occurring in boys. The difference was less pronounced among newborns without severe bacterial infection, where 55% were male.\u003c/p\u003e \u003cp\u003eIn our sample, 13 (76%) of the 17 febrile neonates with SBI were \u0026le;\u0026thinsp;21 days old at admission. Additionally, 100% (n\u0026thinsp;=\u0026thinsp;4) of the IBI cases were in this age group. No perinatal SBI were observed in neonates\u0026thinsp;\u0026le;\u0026thinsp;7 days, though the sample size was small. The prevalence of SBI decreased with age. These findings are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The four febrile neonates with SBI\u0026thinsp;\u0026gt;\u0026thinsp;21 days had a UTI, all with pyuria.\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\u003ePrevalence of Severe Bacterial Infection by Age Group (N\u0026thinsp;=\u0026thinsp;190)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group (days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of neonates\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber with severe bacterial infection (% within age groupe)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0 to 7 days\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\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8 to 14 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15 to 21 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (13.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22 to 28 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5%)\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\u003e190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFor febrile neonates without SBI, routine nasopharyngeal swabs and cerebrospinal fluid analyses identify viruses in most cases.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eSBI affected 9% (n\u0026thinsp;=\u0026thinsp;17) of the 190 febrile neonates studied, which is below the 11\u0026ndash;25% range reported in the literature (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConsistent with data from published studies, the majority were \u003cem\u003eEscherichia coli\u003c/em\u003e UTIs and affected boys. The prevalence of urinary tract infections in the sample (15/190, 8%) corresponds to the lower limit of the 10\u0026ndash;15% range indicated in larger studies of febrile neonates in the emergency department. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) The 13% (2/15) of urosepsis cases among UTIs exceeded the 1,5 to 4% observed in a larger series (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSymptoms such as cough, nasal congestion, and rhinorrhea where associated with a lower risk of SBI. However, caution is warranted for male newborns without these symptoms or with a fever above 38.5\u0026deg;C, or when fever is observed in the emergency department. Given the prevalence of severe bacterial infections and the nonspecific nature of clinical signs, management should not rely solely on clinical evaluations.\u003c/p\u003e \u003cp\u003eIn our study, CRP had limited sensitivity for detecting SBI. Among febrile neonates with SBI, five of 17 had CRP levels below 20 mg/L, and two of four IBI cases had CRP levels below 10 mg/L, including one immunocompromised newborn. The retrospective nature of the study prevented inclusion of the time between fever onset and emergency department admission in this analysis. Although Procalcitonin has been shown to be superior in diagnosing severe bacterial infections, especially meningitis and bacteremia, CRP remains the best biomarker when Procalcitonin is not routinely available. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) Notably, urine analyses reliably identified SBI, particularly UTIs. As highlighted in the literature, UTIs were more prevalent in males (11%) than in females (3.7%) among newborns (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt is crucial to consider that underlying conditions may be present but undiagnosed, especially in neonates. Notably, the only case of bacterial meningitis during this retrospective period involved a child in whom an undiagnosed innate immune deficiency due to a MyD88 mutation was discovered. This mutation, which encodes a protein essential for immune signaling, has been reported in 24 cases to date (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition to potential undiagnosed underlying conditions, antibiotic resistance is another critical factor. The high prevalence of ampicillin-resistant bacteria (64% in SBI and 73% in UTIs) is likely attributable to widespread intrapartum penicillin use to prevent \u003cem\u003eStreptococcus agalactiae\u003c/em\u003e infection in university hospitals in Brussels and globally (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eIs Amoxicilline Still Indicated?\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDuring the retrospective period, no cases of \u003cem\u003eListeria monocytogenes\u003c/em\u003e or \u003cem\u003eEnterococcus\u003c/em\u003e infections were detected among febrile neonates. The literature suggests a declining prevalence (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Despite this trend, Belgian University Hospitals continue to follow empirical dual therapy with ampicillin and cefotaxime, other European centers recommend cefotaxime and an aminoglycoside pending culture results. Given the single-center, retrospective design of this study, adopting a similar strategy during the study period could have been justifiable, though caution is needed when interpreting these results. Aminoglycosides' rapid bactericidal action and renal elimination help limit the selection of resistant mutants, while once-daily dosing offers an advantage. However, caution is required due to potential renal and auditory toxicity.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLowering the Age for Routine Lumbar Puncture to 21 Days: A Possibility?\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe data from Martinez et al. suggest that an automatic lumbar puncture is not required in febrile neonates over 21 days of age who appear healthy and have a negative infectious work-up. However, it remains strongly recommended for febrile neonates under 21 days of age (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). This approach was validated in a prospective multicenter study by Gomez et al., in which procalcitonin was used as a marker of infection (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). The findings from our retrospective study suggest that performing lumbar puncture and administering empirical antibiotic therapy exclusively to febrile neonates\u0026thinsp;\u0026le;\u0026thinsp;21 days would have been a reasonable strategy, which, over the 3-year study period, would not have put our patients at greater risk. No IBI cases were observed in the \u0026le;\u0026thinsp;21-day age group. The four cases of SBI in neonates older than 21 days were UTIs with pyuria and would, therefore, have been managed without lumbar puncture and treated empirically.\u003c/p\u003e \u003cp\u003eThis approach could reduce iatrogenic complications, procedural pain, dosing errors, and unnecessary treatments resulting from false positives. One factor not analyzed in this study is the psychosocial impact of hospitalizing febrile neonates, which can be costly, generate considerable anxiety for parents, and disrupt breastfeeding (\u003cspan additionalcitationids=\"CR40 CR41\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral potential biases must be acknowledged in this study. First, the exclusive selection of neonates admitted to the emergency department of HUDERF for fever could introduce selection bias, excluding other cases. Additionally, the retrospective nature of the study may have introduced recall bias due to potentially incomplete or inaccurate medical records. Data collection could also introduce information bias that might affect the quality of the data. Finally, the results from a single institution may not be generalizable to other settings. Awareness of these biases is crucial for the accurate interpretation of the results.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn summary, SBIs were less common in the studied febrile neonates than previously reported, with \u003cem\u003eEscherichia coli\u003c/em\u003e UTIs identified as the predominant cause. Greater vigilance is needed for male febrile neonates without cough or rhinorrhea However, clinical management should not rely solely on these factors.\u003c/p\u003e \u003cp\u003eCRP is a useful biomarker, but its sensitivity for the early detection of severe bacterial infections is limited. High ampicillin resistance was observed, possibly because of intrapartum prophylaxis. Considering the option of clinical re-evaluation without lumbar puncture in febrile neonates with negative work-up and older than 21 days old is probably interesting.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCFU/mL\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Colony-Forming Units per Milliliter\u003c/p\u003e\n\u003cp\u003eCRP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;C-Reactive Protein\u003c/p\u003e\n\u003cp\u003eED\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Emergency Department\u003c/p\u003e\n\u003cp\u003eESBL\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Extended-Spectrum Beta-Lactamase\u003c/p\u003e\n\u003cp\u003eHUDERF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hôpital Universitaire des Enfants Reine Fabiola\u003c/p\u003e\n\u003cp\u003eIBI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Invasive Bacterial Infection\u003c/p\u003e\n\u003cp\u003ePCR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Polymerase Chain Reaction\u003c/p\u003e\n\u003cp\u003eSBI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Severe Bacterial Infection\u003c/p\u003e\n\u003cp\u003eUTI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Urinary Tract Infection\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFrom the *\u0026nbsp;Emergency Department, Queen Fabiola Pediatric University Hospital, Universit\u0026eacute; Libre de Bruxelles, Brussels, Belgium; \u0026dagger; Department of Pediatrics, Infectious Disease Unit, Brussels University Hospital, Academic Children Hospital Queen Fabiola, Universit\u0026eacute; Libre de Bruxelles, Brussels, Belgium; \u0026Dagger; Molecular Bacteriology Laboratory, European Plotkin Institute for Vaccinology, Universit\u0026eacute; Libre de Bruxelles, Brussels, Belgium;\u003c/p\u003e\n\u003cp\u003eThe authors have declared that no competing interests exist. This study did not receive any funding. All pertinent data are available in both the paper and its accompanying Supporting Information files.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthor Contributions: SJ provided the initial idea for the project and assisted in data analysis. IR assisted in data collection. IR, SJ, and PS reviewed the manuscript. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCorrespondence to: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the HUDERF Ethics Committee (reference 01/23), in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand Funding\u003c/strong\u003e The authors have declared that no competing interests exist. This study did not receive any funding.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe data that support the findings of this study are available from Jules Lagrou ([email protected]) upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGomella T, Eyal F, Bany-Mohammed F (2020) Gomella\u0026rsquo;s Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs. 8e \u0026eacute;d. McGraw-Hill Education, New York\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNewborn health [Internet] [cited 2024 Nov 15]. 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Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=FR\u0026amp;data_id=18313\u0026amp;Disease_Disease_Search_diseaseType=ORPHA\u0026amp;Disease_Disease_Search_diseaseGroup=183713\u0026amp;Maladie(s)/groupes%20de%20maladies=Deficit-en-MyD88\u0026amp;title=Deficit-en-MyD88\u0026amp;search=Disease_Search_Simple\u003c/span\u003e\u003cspan address=\"https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=FR\u0026amp;data_id=18313\u0026amp;Disease_Disease_Search_diseaseType=ORPHA\u0026amp;Disease_Disease_Search_diseaseGroup=183713\u0026amp;Maladie(s)/groupes%20de%20maladies=Deficit-en-MyD88\u0026amp;title=Deficit-en-MyD88\u0026amp;search=Disease_Search_Simple\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Chan PHY, Lau HYS, Tsoi K, Lam HS (2023) Epidemiologic Changes of Neonatal Early-onset Sepsis After the Implementation of Universal Maternal Screening for Group B Streptococcus in Hong Kong. Pediatr Infect Dis J 42(10):914\u0026ndash;920\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNogacka A, Salazar N, Su\u0026aacute;rez M, Milani C, Arboleya S, Sol\u0026iacute;s G et al (2017) Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates. Microbiome 5(1):93\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArboleya S, Saturio S, Gueimonde M (2022) Impact of intrapartum antibiotics on the developing microbiota: a review. Microbiome Res Rep 1(3):22\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiselli F, Cuoghi Costantini R, Creti R, Sforza F, Fanaro S, Ciccia M et al (2022) Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis. Microorganisms 10(10):1878\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHassoun A, Stankovic C, Rogers A, Duffy E, Zidan M, Levijoki C et al (2014) Listeria and Enterococcal Infections in Neonates 28 Days of Age and Younger: Is Empiric Parenteral Ampicillin Still Indicated? Pediatr Emerg Care 30(4):240\u0026ndash;243\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartinez E, Mintegi S, Vilar B, Martinez MJ, Lopez A, Catediano E et al (2015) Prevalence and predictors of bacterial meningitis in young infants with fever without a source. Pediatr Infect Dis J 34(5):494\u0026ndash;498\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGomez B, Mintegi S, Bressan S, Da Dalt L, Gervaix A, Lacroix L et al (2016) Validation of the Step-by-Step Approach in the Management of Young Febrile Infants. Pediatrics 138(2):e20154381\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe S, Tong A, Isaacs D, Craig JC (2014) Parental perspectives on evaluation and management of fever in young infants: an interview study. Arch Dis Child 99(8):717\u0026ndash;723\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalnizky Soffer G, Siri M, Mangel L, Mandel D, Lubetzky R (2020) Impact of Maternal Anxiety on Human Milk Macronutrients Content: A Prospective Observational Study. Breastfeed Med 15(9):572\u0026ndash;575\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Der Velden FJS, Lim E, Smith H, Walsh R, Emonts M (2024) Quantifying the costs of hospital admission for families of children with a febrile illness in the North East of England. BMJ Paediatr Open 8(1):e002489\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed EA (2024) Psychological impact of hospitalization on child and family and the role of nursing care. Int J Psychol Sci 6(1):97\u0026ndash;102\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Febrile neonate, severe bacterial infection, invasive bacterial infection, antibiotic resistance, C-reactive protein","lastPublishedDoi":"10.21203/rs.3.rs-6844796/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6844796/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eThis study aimed to assess the epidemiology and diagnosis of severe bacterial infections in febrile neonates brought to the emergency department.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted a retrospective review of medical records from neonates aged 28 days or younger admitted for fever to the emergency department of a Belgian tertiary hospital between January 2020 and December 2022.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong 190 febrile neonates, 17 (9%) were diagnosed with a severe bacterial infection. Most were urinary tract infections (15 cases), mainly caused by \u003cem\u003eEscherichia coli\u003c/em\u003e. Four neonates (2%) had invasive bacterial infections: one \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e meningitis, one \u003cem\u003eStaphylococcus aureus\u003c/em\u003e bloodstream infection, and two urinary tract infections with concomitant bacteremia. Twelve of the 17 pathogens (71%) showed resistance to at least one antibiotic. Three neonates with severe bacterial infections, including two with invasive disease, had a CRP level below 10 mg/L at admission. Male neonates were at higher risk of bacterial infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eSevere bacterial infections were less frequent than expected, with \u003cem\u003eEscherichia coli\u003c/em\u003eurinary tract infections predominating. CRP was not a reliable marker for invasive disease. These findings support a targeted and individualized approach to antibiotic use and suggest that, in neonates older than 21 days with reassuring initial evaluation, close follow-up may be considered over systematic lumbar puncture.\u003c/p\u003e","manuscriptTitle":"Neonatal Fever in the Emergency Department A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-04 10:25:00","doi":"10.21203/rs.3.rs-6844796/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-18T11:46:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-16T23:54:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-16T23:39:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2025-06-07T22:48:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"10181ad4-fe02-4a88-aa8e-0cf020181a4d","owner":[],"postedDate":"July 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-13T16:07:33+00:00","versionOfRecord":{"articleIdentity":"rs-6844796","link":"https://doi.org/10.1007/s00431-025-06527-5","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2025-10-11 15:58:18","publishedOnDateReadable":"October 11th, 2025"},"versionCreatedAt":"2025-07-04 10:25:00","video":"","vorDoi":"10.1007/s00431-025-06527-5","vorDoiUrl":"https://doi.org/10.1007/s00431-025-06527-5","workflowStages":[]},"version":"v1","identity":"rs-6844796","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6844796","identity":"rs-6844796","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}