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Daniels J, Walker K, Bradshaw L, Dorling J, Ojha S, Gray J, Thornton J, Plumb J, Petrou S, Madan J, Achana F, Ayers S, Constantinou G, Mitchell EJ, Downe S, Grace N, Plachcinski R, Cooper T, Moore S, Jones AM, Harrison E, Brooks J, Barker-Williams K, Hollands H, Mcleavey SK, Willson S, Webster S, Carpenter J, Hyslop-Peart M, Wills L, Haines R, Haydock R, Sadiq S, Fiaschi L, Evans L, Ogollah R, Seale J, Spas S, Huang L, Moody S, Abramson J, GBS 3 Collaborative Group. Routine testing for group B streptococcus in pregnancy: protocol for a UK cluster randomised trial (GBS3). BMJ Open 2025; 15:e087887. [PMID: 40527563 DOI: 10.1136/bmjopen-2024-087887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Collaborators] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/19/2025] Open
Abstract
INTRODUCTION It is unclear whether routine testing of women for group B streptococcus (GBS) colonisation either in late pregnancy or during labour reduces early-onset neonatal sepsis, compared with a risk factor-based strategy. METHODS AND ANALYSIS Cluster randomised trial. SITES AND PARTICIPANTS 320 000 women from up to 80 hospital maternity units. STRATEGIES Sites will be randomised 1:1 to a routine testing strategy or the risk factor-based strategy, using a web-based minimisation algorithm. A second-level randomisation allocates routine testing sites to either antenatal enriched culture medium testing or intrapartum rapid testing. Intrapartum antibiotic prophylaxis will be offered if a test is positive for GBS, or if a maternal risk factor for early-onset GBS infection in her baby is identified before or during labour. Economic and acceptability evaluations will be embedded within the trial design. OUTCOMES The primary outcome is all-cause early (<7 days of birth) neonatal sepsis, defined as either a positive blood/cerebrospinal fluid culture, early neonatal death from infection or a negative/unknown culture status with ≥3 agreed clinical signs or symptoms, who receive intravenous antibiotics ≥5 days. All women giving birth ≥24 weeks' gestation, regardless of mode of birth, and all her babies will be included in the dataset. Cost-effectiveness will be expressed in terms of incremental cost per case of early neonatal sepsis avoided and incremental cost per quality-adjusted life-year associated with each strategy. ETHICS AND DISSEMINATION The trial received a favourable opinion from Derby Research Ethics Committee on 16 September 2019 (19/EM/0253). The allocated testing strategy will be adopted as standard clinical practice by the site. Women in the routine testing sites will give verbal consent for the test. The trial will use routinely collected data retrieved from National Health Service databases, supplemented with limited participant-level collection of process outcomes. Individual written consent will not be sought. The trial results, and parallel economic, qualitative, implementation and methodological results, will be published in the journal Health Technology Assessment. TRIAL REGISTRATION NUMBER ISRCTN49639731.
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Affiliation(s)
- Jane Daniels
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Kate Walker
- Centre for Perinatal Research (CePR), University of Nottingham, Nottingham, UK
| | - Lucy Bradshaw
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Jon Dorling
- Neonatal Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Shalini Ojha
- Centre for Perinatal Research (CePR), University of Nottingham, Nottingham, UK
| | - James Gray
- Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Jim Thornton
- Centre for Perinatal Research (CePR), University of Nottingham, Nottingham, UK
| | - Jane Plumb
- Group B Strep support, Haywards Heath, UK
| | - Stavros Petrou
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Jason Madan
- Warwick Medical School, University of Warwick, Coventry, UK
| | - Felix Achana
- Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
| | - Susan Ayers
- School of Health & Psychological Sciences, City St George's University of London, London, UK
| | - Georgie Constantinou
- School of Health & Psychological Sciences, City St George's University of London, London, UK
| | - Eleanor J Mitchell
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Soo Downe
- School of Nursing and Midwifery, University of Central Lancashire, Preston, UK
| | - Nicola Grace
- Grace Academy of Midwifery and Birth, Nottingham, UK
| | - Rachel Plachcinski
- National Childbirth Trust, London, UK
- Independent Parent and Public Involvement Consultant, Dewsbury, UK
| | | | - Sarah Moore
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Anne-Marie Jones
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Eleanor Harrison
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Joanne Brooks
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | | | - Heidi Hollands
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | | | - Seren Willson
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Sophie Webster
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Jodi Carpenter
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Meg Hyslop-Peart
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Louise Wills
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Rachel Haines
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Rebecca Haydock
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Shabina Sadiq
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Linda Fiaschi
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Lisa Evans
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Reuben Ogollah
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Jay Seale
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Susanne Spas
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Lixiao Huang
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Sebastian Moody
- Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK
| | - Janine Abramson
- School of Medicine, University of Nottingham, Nottingham, UK
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Collaborators
Ihab Abbasi, Rezan Abdul-Kadir, Phern Adams, Rebecca Adcock, Dipika Aggarwal, Hazel Alexander, Dawn Althorn, Sarah-Jayne Ambler, Michelle Anderson, David Ankers, Rita Arya, Karen Austin Smith, Angela Ayuk, Paul Ayuk, Philip Banfield, Jade Barnes, Phillip Bennett, Abbie Berry, Linda Bishop, Patrick Bose, Nichola Brannen, Catherine Bressington, Janet Brown, Lorraine Bullett, Anneka Burch, Jennifer Burrage, Jenny Butler, Anna Campbell, Viv Cannons, Philippa Cansell, Cristina CarballoDe Dios, Jodi Carpenter, Gail Castle, Yee Yin Chan, Floria Cheng, Joanna Clark, Naomi Coleman, Rachael Copley, Janet Cresswell, Yvette Davis, Bashir Dawlaty, Kara Dent, Lisa Ditchfield, Caroline Dixon, Kerry Dooley, Milli Edwards, Sue Fagg, Anam Fayadh, Jo Ficquet, Nicola Flint, Jonathan Ford, Natasha Ford, Lily French, Edward Frew, Rachel Frowd, Ruta Gada, Emma Gammin, Ramesh Ganapathy, Harry Gibson, Joanna Gibson, Caitlin Giles, Mandy Gill, Coralie Glenn-Sansum, Julie Goddard, Jenna Gould, Charlotte Goumalatsou, Sharon Gowans, Elena Greco, Naomi Grimes, Zoe Grindley, Katherina Gross-Gibbs, Liliana Grosu, Lara Robles Gutierrez, Bev Hammond, Latifah Harris, Kathryn Haviland, Holly Hawkesford, Carly Hayton, Miss Mandira Hazra, Anne Marie Henshaw, Jemima Hepburne-Scott, Lesley Hewitt, Kim Hinshaw, Stephanie Horridge, Victoria Hodgson, Heidi Hollands, Rhiannon Hurll, Alison Hylton-Potts, Karen Ixer, Sara Jaarour, Laura Johns, Laura Johnson, Andie Johnson, Linda Johnson, Prudence Jones, Kelly Jukes, Sumit Kar, Pallavi Karkhanis, Tracey Kay, Stephen Keay, Alex Keen, Alex Keen, Joanne Kellett, Mary Kelly- Baxter, Teresa Kelly, Vanessa Kemp, Asma Khalil, Erum Khan, Magdalena Kierzenkowska, Aly Kimber, Eva Kisakye, Sarah Knights, Wiece Koniman, Emmanouil Kountouris, Egi Krasniqi, Maggie Lai, Katie Lang, Sarah Lee, Rebecca Leon, Isabel Llopis, Leanne Lowe, Saswati Maitra, Jodie Manning, Sarah Mapplebeck, Cathryn Marsh, Emily Marler, Ruth Mason, Stephy Mathen, Ilenia Mazzoli, Joanna Mead, Emma Meadows, Michal Rosie Meroz, Hannah Mitchell, Tommy Mousa, Hannah Mugford, Hannah Mullins, Eric Mutema, Bonilla Nayar, Jonathan Nelson, Rachel Newport, Shari Noraiee, Justine Nugent, Nzoputa Nwabueze, Chinwe Obiozo-Jumbo, Clare O'Brien-Hirst, Anne-Marie O'Brien, Tanwa Ogbara, Chloe O'Hara, Oyinlola Okungade, Chidera Onyeagor, Lola Oshodi, Hilary Owen, Louise Page, Hannah Parker, Sam Parlapalli, Leia Parry, Nikky Passmore, Sangeeta Pathak, Tara Pauley, Linda Peacock, Carol Percy, Janet Phipps, Helen Preston, Ella Proctor, Emma Pugh, Madhavi Pureti, Eleanor Pyart, Vinita Raheja, Clair Rainford, Miss Jyothi Rajeswary, Guduru Gopal Rao, Lindsay Roughley, Ruth Ryder, Maiti Sachchidananda, Ferha Saeed, Beena Saji, Manjula Samyraju, Emily Scriven, Jess Sellick, Ellie Didier Serre, Erikka Siddall, Jonathan Slack, Trudy Smith, Catherine Stone, Delphine Strub, Louise Swaminathan, Emma Tanton, Vasso Terzidou, Niki Thatcher, Catherine Townsend, Lydia Ufton, Lilian Ugwumadu, Ureh Umeh-John, Laura Veal, Kate Walker, Julie Walker, Husswan Yasmin WanHussein, Heather Ward, Annie Warrington, Sarah Watson, Sophie Webster, Sharon Westcar, Hayley Wheeler, Sonia White, Anna Williams, Seren Willson, Jessica Wilson, Miss Frances Wood, Julie Woollaston, Janet Wright, Priti Wuppalapati, Cheryl Wyatt, Alex Taylor, Jemma Yorke, Kate Young, Rabia Zill-E-Huma,
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Dai J, Xia B, Liu N, Shui P. CAUSAL ASSOCIATION BETWEEN SEPSIS AND FIBROBLAST GROWTH FACTORS AS WELL AS THEIR RECEPTORS LEVELS: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY. Shock 2025; 63:836-843. [PMID: 40138723 DOI: 10.1097/shk.0000000000002565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
ABSTRACT Objective: The potential association between sepsis risk and circulating levels of fibroblast growth factors (FGFs) and their receptors (FGFRs) has been a focus of research; however, the causal relationship between them remains to be elucidated. We hypothesize a causal association between genetically predicted FGFs, FGFRs, and sepsis risk, and we conduct a Mendelian randomization (MR) study to validate this hypothesis. Methods: We utilized a two-sample MR design to assess the effect of genetic variants associated with various FGFs (FGF1, FGF2, FGF7, FGF16, FGF19, FGF21, FGF23, FGF5) and FGFRs (FGFR1, FGFR2, FGFR3, α-Klotho) on sepsis risk, using genome-wide association study summary statistics. Our MR analyses employed the inverse-variance weighted (IVW) method, along with weighted median, weighted mode, and MR-Egger regression, supplemented by sensitivity analyses to ensure robustness. Results: The MR analysis identified an unequal number of instrumental variables ranging from 2 to 17 for FGFs and FGFRs when sepsis was the outcome. No significant correlation was found between genetically determined FGF levels and sepsis risk by IVW analysis (all P > 0.05). Correspondingly, similar nonsignificant associations were observed for FGFRs (all P > 0.05). Other MR methods corroborated the IVW findings. Sensitivity analyses, including Cochran's Q test, MR-Egger, and MR pleiotropy residual sum and outlier, indicated no significant heterogeneity or pleiotropy in the relationships, with the exception of a nonsignificant correlation between FGFR1 and sepsis that persisted after the exclusion of an outlier (odds ratio, 0.84; P = 0.34). Conclusion: The analysis found no significant causal associations between FGFs, their receptors, and sepsis risk, indicating a need for further research on their complex interactions.
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Affiliation(s)
- Junru Dai
- Emergency Department, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, China
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3
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Affichard F, Brunet S, El Hage C, Julliand S, Lode N, Genuini M. Prospective Evaluation of Adherence to French Guidelines on Early Onset Sepsis Management. Pediatr Infect Dis J 2025; 44:506-510. [PMID: 39889732 DOI: 10.1097/inf.0000000000004708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2025]
Abstract
BACKGROUND Early onset sepsis (EOS) is rare but potentially lethal. French guidelines were published in 2017 to improve the care of children. The aim of this study was to qualify and quantify inadequate antibiotic therapy management compared with the recommendations made by the new French guidelines. METHODS This prospective observational study was conducted at the Robert Debré Hospital (Paris, France), a tertiary pediatric teaching center. Data were prospectively collected between May and October 2019. We included all neonates born at a gestational age ≥ 34 weeks who needed emergency transportation by the pediatric intensive care unit transport team during the first 72 hours of life. The primary outcome was the rate of antibiotic therapy initiation (or abstention) that did not respect the new French guidelines. RESULTS One hundred and seven patients were included. The median gestational age was 39 weeks and 6 days. Median weight was 3355 g. Fifty-eight births (54%) had at least 1 risk factor for EOS. Ninety-seven (91%) infants had at least 1 symptom of EOS, and 76 (71%) were treated with antibiotics. Three newborns (3%) had a documented EOS, and all of them survived. Antibiotic therapy initiation or abstention was adequate for 91% of our cohort (n = 107). Physicians prescribed inadequate biologic tests for 67 (63%) infants. CONCLUSIONS There was a high adherence to the French EOS guidelines for antibiotic therapy initiation or abstention. No death related to EOS occurred in our cohort. Nevertheless, a high proportion of children had undergone inadequate biological tests.
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Affiliation(s)
- Florine Affichard
- From the Pediatric Intensive Care Transport Team, Hôpital Robert Debré
| | - Stéphanie Brunet
- From the Pediatric Intensive Care Transport Team, Hôpital Robert Debré
- Neonatal Intensive Care Unit, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, Université Paris, Paris, France
| | | | | | - Noella Lode
- From the Pediatric Intensive Care Transport Team, Hôpital Robert Debré
| | - Mathieu Genuini
- From the Pediatric Intensive Care Transport Team, Hôpital Robert Debré
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Zhou J, Huo H, He R, Lu Y, Peng Y, Zou X, Jiang S. Age-related stress gene expression in neonatal sepsis involves regulatory networks and immune cell infiltration. Sci Rep 2025; 15:18814. [PMID: 40442112 PMCID: PMC12122668 DOI: 10.1038/s41598-025-01442-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 05/06/2025] [Indexed: 06/02/2025] Open
Abstract
Septicemia triggers a profound systemic inflammatory response, ultimately leading to cellular senescence. Understanding the mechanisms underlying intercellular interactions associated with sepsis is crucial for developing therapeutic strategies targeting sepsis and its associated complications. Neonatal septicemia (NS) is a critical condition characterized by systemic infection in newborns. Currently, there are no effective indicators for the early identification of sepsis and precise screening of newborns who truly require antibiotic treatment, which results in delayed diagnosis of neonatal sepsis and the overuse of antibiotics. We aimed to elucidate cellular senescence-related genes (CSRGs) in the context of NS and to investigate their potential regulatory networks and immune infiltration patterns. Our analysis identified 391 DEGs, including 301 upregulated and 90 downregulated genes and 15 differentially expressed CSRGs (CSRDEGs), including STAT3, MAPK14, IGFBP7, PPARG, and ETS2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed enrichment in biological processes, including cellular senescence, and pathways involving PD-L1 expression in cancer. Gene Set Enrichment Analysis highlighted significant pathways, including selenoamino acid metabolism and neutrophil degranulation. Protein-protein interaction network analysis identified eight hub genes: STAT3, MAPK14, CEBPB, TLR2, ETS1, JUNB, PPARG, and MAP3K5. Regulatory network analysis revealed interactions between CSRDEGs and multiple transcription factors/miRNAs. Immune infiltration analysis revealed profound differences in the composition of immune cells between the normal and NS groups. Our study findings offer valuable information for future research on therapeutic targets and diagnostic markers of NS.
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Affiliation(s)
- Jenny Zhou
- Neonatal Department, The First People's Hospital of Foshan City, Foshan, Guangdong, China
| | - Huiyi Huo
- Neonatal Department, The First People's Hospital of Foshan City, Foshan, Guangdong, China
| | - Ruth He
- Neonatal Department, The First People's Hospital of Foshan City, Foshan, Guangdong, China
| | - Yongxue Lu
- Neonatal Department, The First People's Hospital of Foshan City, Foshan, Guangdong, China
| | - Yunju Peng
- Neonatal Department, The First People's Hospital of Foshan City, Foshan, Guangdong, China
| | - Xiaoping Zou
- Neonatal Department, The First People's Hospital of Foshan City, Foshan, Guangdong, China
| | - Suhua Jiang
- Neonatal Department, The First People's Hospital of Foshan City, Foshan, Guangdong, China.
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Assaifan AK, Alfadul H, Albuaimi MS, Alrebaish AS, Al-Gawati M. Scalable flexographic printing of graphite/carbon dot nanobiosensors for non-faradaic electrochemical quantification of IL-8. Talanta 2025; 295:128371. [PMID: 40412198 DOI: 10.1016/j.talanta.2025.128371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/28/2025] [Accepted: 05/20/2025] [Indexed: 05/27/2025]
Abstract
Interleukin-8 (IL-8) is a key biomarker linked to inflammation and disability in neonates. However, current IL-8 detection methods are often costly, labor-intensive, and require highly trained personnel. While electrochemical techniques have been employed for sensitive IL-8 quantification, they typically rely on redox probes and three-electrode electrochemical cells, leading to issues such as toxicity, prolonged fabrication time, and increased waste generation. Additionally, conventional electrochemical biosensors fabrication techniques are expensive and time-consuming, limiting their scalability for mass disease screening. In this study, we introduce a low-cost, non-faradaic electrochemical nanobiosensor for the direct detection of IL-8. The sensor consists of interdigitated graphite/carbon dot conjugates flexographically printed onto a flexible polyimide substrate. The printed layer's physical properties were systematically characterized using SEM, AFM and surface profilometer, and biofunctionalization was achieved using aminopropyltriethoxysilane (APTES) and glutaraldehyde. Successful surface modification was confirmed through ATR-FTIR and EDS elemental mapping. Electrochemical impedance spectroscopy (EIS) analysis demonstrated the nanobiosensor's response to varying IL-8 concentrations, with capacitance, Zmod, Zreal, and Zimag measurements. Among these, Zimag exhibited the highest sensitivity, with a response of 2.7 kΩ/log(ng/mL) and a detection limit of 50 pg/mL-well below the clinically established threshold of 600 pg/mL. This study demonstrates that, in addition to capacitance, there are multiple parameters that warrant exploration in non-faradaic biosensors to improve their sensing performance. The nanobiosensor fabrication via flexographic printing enables scalable, cost-effective production while maintaining high sensitivity and selectivity through a non-faradaic detection mechanism. This work paves the way for the development of affordable, mass-producible biosensors for early biomarker detection, facilitating timely medical intervention and improved neonatal healthcare outcomes.
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Affiliation(s)
- Abdulaziz K Assaifan
- Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia; King Salman Center for Disability Research, Riyadh, 11614, Saudi Arabia; Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
| | - Hend Alfadul
- Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia; Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia
| | - Munira S Albuaimi
- Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia; Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia
| | - Abdulelah S Alrebaish
- Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia
| | - Mahmoud Al-Gawati
- Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia
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Rubio-Mora E, Bloise-Sánchez I, Quiles-Melero I, Cacho-Calvo J, Cendejas-Bueno E. Neonatal sepsis: Epidemiology and comparison between preterm and term newborns. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2025; 43:197-204. [PMID: 40180474 DOI: 10.1016/j.eimce.2025.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 07/15/2024] [Indexed: 04/05/2025]
Abstract
INTRODUCTION Neonatal sepsis is a severe clinical syndrome that continues to be a common and significant health care burden. Knowledge of the local epidemiology allows for a better empirical treatment and improves morbidity and mortality. The aim of this study was to determine the prevalence, epidemiology, and etiology of blood culture-proven sepsis in neonates and to determine whether there are differences between preterm and term newborns. METHODS A retrospective study was carried out in a tertiary hospital in Madrid, Spain, during 2021, including 1443 patients at risk of developing sepsis. RESULTS The majority of sepsis episodes occurred in preterm newborns (64.81%) and most of them were very low birth weight infants (74.29%). Late-onset sepsis represented 94.92% of all the episodes reported with an incidence of 11.4 (95% CI 8.8-14.8) per 1000 live newborns. Early onset sepsis incidence was 0.6 (95% CI 0.2-1.8) per 1000 live newborns. Coagulase-negative staphylococci took the first place as causative agents of sepsis (66.10%), causing in all the episodes late onset catheter-related bloodstream infection. When the newborns who developed sepsis were compared with those who did not developed sepsis, the presence of venous/arterial access device was significantly associated with sepsis in both preterm (odds ratio (OR) 8.12, 95% CI 0.47-141.40) and term newborns (OR 16.58, 95% CI 1.00-275.20). Recent surgery was nevertheless the main risk factor in term newborns (OR 45.29, 95% CI 13.70-149.70). Among those patients who developed sepsis, no differences between preterm and term newborns were found regarding time onset, mechanism of transmission, etiological agents, and mortality. A 100% of the preterm and 42.11% of the term newborns presented two or more risk factors. The mortality rate observed here has been 1.85% (95% CI 0.33-9.77%). CONCLUSION The main risk factors for sepsis were venous/arterial access device (for both preterm and term newborns) and recent surgery (term newborns). Prematurity and being a catheter carrier were strongly associated with late-onset neonatal sepsis, mainly due to coagulase-negative staphylococci. The mortality rate was lower than that observed in other high-income countries.
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Affiliation(s)
- Eduardo Rubio-Mora
- Servicio de Microbiología y Parasitología, Hospital Universitario La Paz, Madrid, Spain
| | - Iván Bloise-Sánchez
- Servicio de Microbiología y Parasitología, Hospital Universitario La Paz, Madrid, Spain
| | | | - Juana Cacho-Calvo
- Servicio de Microbiología y Parasitología, Hospital Universitario La Paz, Madrid, Spain
| | - Emilio Cendejas-Bueno
- Servicio de Microbiología y Parasitología, Hospital Universitario La Paz, Madrid, Spain.
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Kounou A, Koudokpon H, Sintondji K, Lègba B, Fabiyi K, Yadouléton A, Saarinen S, Dougnon V. Prevalence and determinants of neonatal infections in Benin based on a retrospective study in six reference hospitals. Sci Rep 2025; 15:11093. [PMID: 40169680 PMCID: PMC11962093 DOI: 10.1038/s41598-025-94442-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 03/13/2025] [Indexed: 04/03/2025] Open
Abstract
Maternal and neonatal infections pose a significant public health challenge, particularly in developing countries like Benin. This retrospective study investigates the frequency and determinants of maternal and neonatal infections in Benin during 2022, utilizing data from six reference hospitals. The study includes 123 neonates suspected of infection, analyzing factors such as birth weight, breastfeeding practices, clinical delivery parameters, and laboratory-confirmed infection rates. Findings reveal that 32% of suspected cases were confirmed infections, with a higher prevalence among premature newborns and those born in specific hospitals. The study emphasizes the need for improved diagnostic facilities, infection control practices, and awareness among healthcare workers and pregnant women. Recommendations for future research include broader geographic coverage and enhanced training programs.
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Affiliation(s)
- Arielle Kounou
- Research Unit in Applied Microbiology and Pharmacology of Natural Substances, Research Laboratory in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Abomey-Calavi, Benin
| | - Hornel Koudokpon
- Research Unit in Applied Microbiology and Pharmacology of Natural Substances, Research Laboratory in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Abomey-Calavi, Benin
| | - Kevin Sintondji
- Research Unit in Applied Microbiology and Pharmacology of Natural Substances, Research Laboratory in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Abomey-Calavi, Benin
| | - Boris Lègba
- Research Unit in Applied Microbiology and Pharmacology of Natural Substances, Research Laboratory in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Abomey-Calavi, Benin
| | - Kafayath Fabiyi
- Research Unit in Applied Microbiology and Pharmacology of Natural Substances, Research Laboratory in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Abomey-Calavi, Benin
| | - Anges Yadouléton
- Viral Hemorrhagic Fevers and Arboviruses Laboratory, Ministry of Health, Benin, Cotonou, Benin
| | | | - Victorien Dougnon
- Research Unit in Applied Microbiology and Pharmacology of Natural Substances, Research Laboratory in Applied Biology, Polytechnic School of Abomey-Calavi, University of Abomey-Calavi, Abomey-Calavi, Benin.
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Mohammadi A, De Luca D, Gauda EB. Characteristics, triggers, treatments, and experimental models of neonatal acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 2025; 328:L512-L525. [PMID: 39924963 DOI: 10.1152/ajplung.00312.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/20/2024] [Accepted: 02/04/2025] [Indexed: 02/11/2025] Open
Abstract
Neonatal acute respiratory distress syndrome (NARDS) is a severe and potentially life-threatening form of lung injury recently defined by the International Neonatal ARDS Consensus. It is marked by extensive lung inflammation and damage to the alveolar epithelium and vascular endothelium. NARDS can be triggered by direct inflammatory exposures, such as pneumonia and aspiration, and indirect exposures, including sepsis, necrotizing enterocolitis, and chorioamnionitis. This review provides clinicians and researchers with the latest insights on NARDS. We adopt a cross-disciplinary approach to discuss the diagnostic criteria, pathobiology, triggers, epidemiology, and treatments of NARDS. In addition, we summarize existing clinical studies and advanced preclinical models that help address current knowledge gaps. Future research should focus on standardizing the Montreux consensus definition of NARDS in preclinical and clinical studies, identifying biomarkers, developing prediction models, and exploring novel therapies for affected infants.
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Affiliation(s)
- Atefeh Mohammadi
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Division of Neonatology and Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Daniele De Luca
- Division of Pediatrics and Neonatal Critical Care, "A. Béclère" Medical Center, Paris - Saclay University Hospitals, APHP, Paris, France
- Physiopathology and Therapeutic Innovation Unit-INSERM U999, Paris Saclay University, Paris, France
| | - Estelle B Gauda
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Division of Neonatology and Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
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9
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Mohajeri P, Faridafshar H, Kooti S. Identification and antimicrobial susceptibility testing of Streptococcus agalactiae associated urinary tract infections using VITEK 2 system. IRANIAN JOURNAL OF MICROBIOLOGY 2025; 17:239-245. [PMID: 40337691 PMCID: PMC12053419 DOI: 10.18502/ijm.v17i2.18383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/09/2025]
Abstract
Background and Objectives As a Gram-positive bacterium, Streptococcus agalactiae or Group B Streptococcus (GBS) is normally found as a transient flora of the gastrointestinal and genitourinary tracts of women. The high prevalence of GBS in the urethra warrants investigation of UTIs and antibiotic resistance frequency associated with GBS. Given the paucity of research on antibiotic resistance of GBS in Iran, the present study investigated the UTIs associated with GBS and the antibiotic susceptibility patterns associated with GBS. Materials and Methods This study included 65 GBS strains collected from urine samples obtained from the Bouali Laboratory Complex, one of the largest laboratories in western Iran. VITEK 2 GP ID cards were used to identify all GBS isolates. VITEK 2 susceptibility testing for Gram-positive bacteria was performed according to the manufacturer's instructions using the AST-ST card. MIC method was performed after the detection of GBS strains. Results We found that 53 (81.5%) of the GBS isolates showed resistance to tetracycline; 47 (72.3%), 40 (61.5%), and 30 (46.15%) of these had a resistance to erythromycin, clindamycin and ampicillin respectively. Conclusion In the present study, the VITEK 2 system was validated as a user-friendly system that can serve as a rapid and accurate tool for identification and antimicrobial susceptibility testing of GBS.
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Affiliation(s)
- Parviz Mohajeri
- Department of Microbiology, School of Medicine, Infectious Diseases Research Center, Research Institute for Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Hossein Faridafshar
- Department of Microbiology, Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sara Kooti
- Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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DeVeaux AL, Hall-Moore C, Shaikh N, Wallace M, Burnham CAD, Schnadower D, Kuppermann N, Mahajan P, Ramilo O, Tarr PI, Dantas G, Schwartz DJ. Metagenomic signatures of extraintestinal bacterial infection in the febrile term infant gut microbiome. MICROBIOME 2025; 13:82. [PMID: 40128855 PMCID: PMC11931804 DOI: 10.1186/s40168-025-02079-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 03/04/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished. RESULTS We studied a cohort of febrile term infants < 60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli infections who were colonized by the putatively isogenic pathogen strain had significantly higher E. coli phylogroup B2 abundance in their gut, and their microbiome was more likely to contain virulence factor loci associated with adherence, exotoxin production, and nutritional/metabolic function. CONCLUSIONS The intestine plausibly serves as a reservoir for EBI pathogens in a subset of febrile term infants, prompting consideration of new opportunities for surveillance and EBI prevention among colonized, pre-symptomatic infants. Video Abstract.
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Affiliation(s)
- Anna L DeVeaux
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
| | - Carla Hall-Moore
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Nurmohammad Shaikh
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Meghan Wallace
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Carey-Ann D Burnham
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - David Schnadower
- Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Nathan Kuppermann
- Departments of Pediatrics and Emergency Medicine, The George Washington School of Medicine and Health Sciences, and Children'S National Hospital, Washington, DC, USA
| | - Prashant Mahajan
- Departments of Emergency Medicine and Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | - Octavio Ramilo
- Department of Infectious Diseases, St. Jude Children'S Research Hospital, Memphis, TN, USA
| | - Phillip I Tarr
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Gautam Dantas
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA
| | - Drew J Schwartz
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
- Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO, USA.
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Jin Y, Guo S, Xiao Y, Yin C. Assessment of the diagnostic significance of pentraxin-3 in conjunction with procalcitonin (PCT) and C-reactive protein (CRP) for neonatal sepsis. BMC Infect Dis 2025; 25:401. [PMID: 40128667 PMCID: PMC11934617 DOI: 10.1186/s12879-025-10821-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 03/18/2025] [Indexed: 03/26/2025] Open
Abstract
OBJECTIVE This study aimed to compare serum levels of pentraxin-3 (PTX-3) in neonates with sepsis against those without sepsis and to assess the diagnostic value of PTX-3 in relation to conventional inflammatory markers. METHODS Between June and December 2020, a total of 109 neonates aged 1 to 21 days, with birth weights ranging from 1795 g to 4200 g, and who met the diagnostic criteria outlined in the "Expert Consensus on the Diagnosis and Treatment of Neonatal Sepsis" (2019) were examined in this prospective study, including 35 with sepsis, 36 with localized infections, and 38 without any infections. Neonates with congenital malformations, intrauterine viral infections, prior antibiotic treatment or without parental consent were excluded from the study. Blood samples were collected and analyzed for routine blood parameters, liver and kidney function metrics, levels of C-reactive protein (CRP), procalcitonin (PCT), lactic acid, and PTX-3. RESULTS The incidence of premature rupture of membranes was significantly lower in the sepsis and localized infection groups compared to the non-infected group (22.86%, 11.11%, and 2.63%; P < 0.05). White blood cell (WBC) counts were significantly elevated in both the sepsis and localized infection groups when compared to the non-infected group (P < 0.05). Notable differences were also found in lactate dehydrogenase (LDH) and calcium (Ca) levels (P < 0.05). Serum levels of CRP, PCT, and PTX-3 were significantly higher in the sepsis group (P < 0.05). Additionally, PTX-3 levels demonstrated a strong correlation with both CRP and PCT (P < 0.01). PTX-3, PCT, and platelet distribution width (PDW) emerged as independent risk factors for neonatal infection, while WBC, platelet count (PLT), CRP, PTX-3, PDW, and pH were identified as independent risk factors for sepsis (P < 0.05). The combination of PTX-3, CRP, PCT, and WBC exhibited the highest diagnostic efficiency for neonatal infection (AUC = 0.954, sensitivity 97.4%, specificity 83.1%; P < 0.01). For sepsis, the combined markers also demonstrated the best diagnostic performance (AUC = 0.855, sensitivity 83.3%, specificity 80.0%; P < 0.01). CONCLUSION PTX-3 shows promise as a biomarker for neonatal sepsis, and when combined with WBC, CRP, and PCT, it significantly enhances both diagnostic sensitivity and specificity. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Yan Jin
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, Shaanxi, 710061, China
- Department of Pediatrics, Shanxi Sengong Hospital, Xi'an, Shaanxi, 200085, China
| | - Shuang Guo
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, Shaanxi, 710061, China
| | - Yanfeng Xiao
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, Shaanxi, 710061, China
| | - Chunyan Yin
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, Shaanxi, 710061, China.
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S.B. J, Baskar S, Fareed M, Kumar KS, Mostafa OE, Bawazir A, AlQumaizi KI. Role of hematological parameters in the early detection of clinical cases for septicemia among neonates: A hospital-based study from Chennai, India. PLoS One 2025; 20:e0318802. [PMID: 40106759 PMCID: PMC11922526 DOI: 10.1371/journal.pone.0318802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 01/21/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Neonatal sepsis, a leading cause of newborn mortality, arises from systemic infections due to an immature immune system. Its subtle early symptoms complicate timely diagnosis. Hematological parameters act as an indicator for early detection, crucial for prompt treatment, improving prognosis, and are not a challenging or cumbersome process. AIM The primary objective was to evaluate the significance of hematological parameters including red blood cell (RBC), WBC, and platelet counts in the context of neonatal sepsis. METHODS This hospital-based cohort study examined 73 neonates admitted to the neonatal intensive care unit (NICU) of Saveetha Medical College and Hospital, Chennai, India during the period of January 2023 to March 2024. All the new born patients were presented with blood culture-confirmed septicemia. RESULTS The investigation identified Klebsiella pneumoniae as the most prevalent etiological agent (26.02%), followed by Coagulase-Negative Staphylococci (CONS) and Acinetobacter baumannii (both 8.2%). Alterations in total leukocyte count and hematocrit were observed in 57% and 68.1% of cases, respectively, providing a prompt indication of infection status. Subsequent analyses revealed prominent leukocytosis, hematocrit irregularities, and thrombocytopenia, frequently manifesting in septic cases and demonstrating potential as early markers for neonatal sepsis. CONCLUSION The study highlights the diagnostic value of hematological alterations, such as leukocytosis and hematocrit distortion, in the prompt identification of septicemia among neonates. Based on the findings, it is recommended that routine hematological screening to be integrated as a standard component of neonatal sepsis diagnosis for rapid investigation of neonatal sepsis.
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Affiliation(s)
- Jeivanth S.B.
- Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai, India
| | - Shreemathee Baskar
- Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai, India
| | - Mohammad Fareed
- Community Medicine Unit, Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, Saudi Arabia
| | - K. Santhosh Kumar
- Department of Neonatology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai, India
| | - Osama Elshahat Mostafa
- Department of Nursing, College of Applied Sciences, AlMaarefa University, Diriyah, Saudi Arabia
| | - Amen Bawazir
- Community Medicine Unit, Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, Saudi Arabia
| | - Khalid I. AlQumaizi
- Department of Family Medicine, College of Medicine, AlMaarefa University, Diriyah, Saudi Arabia
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Al-Shehab M, Abdul-Ghani R, Elnemr M, Al-Qadasi F, Alabsi G, Farie W, Alghafari Y. Comparison of risk factors, clinical characteristics, laboratory findings and bacterial etiology between early-onset and late-onset neonatal sepsis in Sana'a City, Yemen. BMC Pediatr 2025; 25:208. [PMID: 40098160 PMCID: PMC11912798 DOI: 10.1186/s12887-025-05553-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 02/26/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Sepsis is a major cause of neonatal mortality worldwide. However, its risk factors, clinical characteristics, laboratory findings, and bacterial etiology vary across countries. Therefore, this study compared these factors between early-onset sepsis (EOS) and late-onset sepsis (LOS) in Sana'a city, Yemen. METHODS A prospective, cross-sectional study was conducted among 156 neonates with suspected sepsis in Sana'a. Data about risk factors, clinical characteristics, and laboratory findings were collected using a data collection sheet, and blood samples were collected for culture according to established procedures. The data were then analyzed at a significance level of < 0.05. RESULTS Of neonates with suspected sepsis, 65.4% had LOS and 34.6% had EOS. However, sepsis was confirmed in 62.2% of cases. Compared to EOS, preterm birth (OR = 4.1, 95% CI: 1.27-13.02; P = 0.013), and exteremely low birthweight (ELBW) and very low birthweight (VLBW) (OR = 4.7, 95% CI: 1.02-22.19; P = 0.033) were significantly associated with a higher risk of LOS, while premature rupture of membranes (PROM) was significantly associated with a lower risk of LOS (OR = 0.2, 95% CI: 0.03-0.99; P = 0.043). Jaundice was significantly more common in neonates with EOS, while apnea was significantly more common in those with LOS. However, no significant differences were found between EOS and LOS in terms of other clinical characteristics, leukocyte and platelet counts, or C-reactive protein (CRP). Gram-positive cocci were the most frequent bacterial isolates (63.9%), with coagulase-negative staphylococci (CoNS) being the predominant species (63.6% in EOS and 42.2% in LOS). Gram-negative bacilli were isolated from 36.1% of cases and were more common in LOS (77.1%) than in EOS (22.9%), with Klebsiella species being the most predominant (19.6%). CONCLUSION Most neonatal sepsis cases in Sana'a are LOS, mostly commonly caused by Gram-positive cocci and associated with preterm birth and ELBW and VLBW. Differences in risk factors associated with EOS and LOS highlight the need for targeted preventive measures in neonatal care settings.
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Affiliation(s)
- Mohammed Al-Shehab
- Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Science and Technology (USTY), Sana'a, Yemen.
- Department of Pediatrics, University of Science and Technology Hospital, Sana'a, Yemen.
| | - Rashad Abdul-Ghani
- Department of Medical Parasitology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
- Tropical Disease Research Center, Faculty of Medicine and Health Sciences, University of Science and Technology (USTY), Sana'a, Yemen.
| | - Muna Elnemr
- Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Science and Technology (USTY), Sana'a, Yemen
| | - Farouk Al-Qadasi
- Migration Health Unit, International Organization for Migration, Sana'a, Yemen
| | - Ghassan Alabsi
- Department of Pediatrics, University of Science and Technology Hospital, Sana'a, Yemen
| | - Waleed Farie
- Department of Medical Laboratories, Faculty of Medicine and Health Sciences, University of Science and Technology (USTY), Sana'a, Yemen
| | - Yahya Alghafari
- Department of Pediatrics, University of Science and Technology Hospital, Sana'a, Yemen
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Haaland K, Goel S, Kumar G, Hurv IA, Thapar I, Jalthuria J, Nangia S. Sharing Milk and Knowledge in the Neonatal Intensive Care Unit Improves Care for Neonates in a Low- and Middle-Income Population-A North-South Collaboration. CHILDREN (BASEL, SWITZERLAND) 2025; 12:326. [PMID: 40150608 PMCID: PMC11940916 DOI: 10.3390/children12030326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/05/2025] [Accepted: 02/11/2025] [Indexed: 03/29/2025]
Abstract
Background: Basic healthcare may significantly decrease neonatal morbidity and mortality. Attention to this, particularly in populations where rates of potentially preventable illness and death within the first weeks of life are extremely high, will have a positive impact on global health. Objective: This manuscript presents the development and impact of a quality improvement programme to reduce the evidence-practice gap in care for neonates admitted to the NICU in a public hospital in India. The programme was locally customised for optimal and sustainable results. Method: The backbone of the project was educational exchange of neonatal nurses and physicians between Norway and India. Areas of potential improvement in the care for the neonates were mainly identified by the clinicians and focus areas were subject to dynamic changes over time. In addition, a service centre for lactation counselling and milk banking was established. Progress over the timeframe 2017-2019 was compared with baseline data. Results: The project has shown that after a collaborative effort, there is a significant reduction in mortality from 11% in the year 2016 to 5.5% in the year 2019. The morbidity was reduced, as illustrated by the decrease in the proportion of neonates with culture-proven sepsis. Nutrition improved with consumption of human milk by the NICU-admitted neonates remarkably increasing from one third to more than three forth of their total intake, and weight gain in a subgroup was shown to increase. With the introduction of family participatory care, hours of skin-to-skin contact for the neonates significantly increased. Additional indicators of improved care were also observed. Conclusions: It is feasible to reduce neonatal mortality and morbidity in a low- and middle-income hospitalised population by improving basic care including nutrition relatively inexpensively when utilising human resources.
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Affiliation(s)
- Kirsti Haaland
- Department of Global Health, Division of Emergencies and Critical Care, Oslo University Hospital, Ullevål, Kirkeveien 166, 0450 Oslo, Norway
- Department of Neonatal Intensive Care, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Ullevål, Kirkeveien 166, 0450 Oslo, Norway
| | - Srishti Goel
- Lifeline Advanced Neonatal Centre, 63 & 64, Cool Road, Waryam Nagar, Jalandhar 144001, Punjab, India;
| | - Gunjana Kumar
- National Institute of Medical Science & Research, NH-11C, Delhi-Jaipur Expressway, Jaipur 303121, Rajasthan, India;
| | - Ingvild Andresen Hurv
- Institute for Nursing, Faculty of Health, VID Specialised University, Theodor Dahls vei 10, 0370 Oslo, Norway
| | - Isha Thapar
- National Comprehensive Lactation Management Centre, Lady Hardinge Medical College, Shaheed Bhagat Singh Marg, Connaught Place, New Delhi 110001, India; (I.T.); (J.J.)
| | - Jitesh Jalthuria
- National Comprehensive Lactation Management Centre, Lady Hardinge Medical College, Shaheed Bhagat Singh Marg, Connaught Place, New Delhi 110001, India; (I.T.); (J.J.)
| | - Sushma Nangia
- Department of Neonatology, Lady Hardinge Medical College, Shaheed Bhagat Singh Marg, Connaught Place, New Delhi 110001, India;
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Wondifraw EB, Wudu MA, Tefera BD, Wondie KY. The burden of neonatal sepsis and its risk factors in Africa. a systematic review and meta-analysis. BMC Public Health 2025; 25:847. [PMID: 40033243 PMCID: PMC11877888 DOI: 10.1186/s12889-025-22076-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 02/24/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND Neonatal sepsis is a significant cause of newborn mortality in low- and middle-income countries (LMICs). Together, infections, complications of preterm birth, and intrapartum-related conditions contribute to nearly 90% of all neonatal deaths. Africa experiences high rates of neonatal deaths due to sepsis, with insufficient prevention efforts. Understanding the burden of neonatal sepsis is essential to reducing these deaths in the region. This study aims to estimate the pooled magnitude of neonatal sepsis and identify its associated risk factors in Africa. METHOD For this study, we gathered data by searching various databases until August 20, 2024, including PubMed/MEDLINE, PubMed Central, Hinari, Google, Cochrane Library, African Journals Online, Web of Science, and Google Scholar. Full-text articles in English, both published and unpublished, from 2000 to 2024 were included. However, sources like citations without abstracts or full texts, unidentified reports, editorials, summaries of research, meta-analyses, and qualitative studies were not included in the study. We evaluated the quality of the selected papers using the Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. Data extraction was completed in Microsoft Excel, and analysis was conducted using STATA V.17 Statistical Software. We assessed study heterogeneity with the I2 statistic and the Cochrane Q test. Publication bias was evaluated both visually through a funnel plot and statistically through Egger's regression and Begg's tests. Subgroup analyses were performed to identify sources of heterogeneity, and a sensitivity analysis was conducted to find any outlier studies. RESULT This review includes 49 studies with 87,548 neonates. The overall magnitude of neonatal sepsis in Africa was found to be 40.98% (95% confidence interval (CI): 30.50% to 51.46%) P: 0.00. The study found that factors such as prolonged rupture of membranes (Odds ratio (OR) 4.11, 95% CI: 2.81-5.41) P: 0.00, a history of the urinary tract or sexually transmitted infections (OR 3.28, 95% CI: 1.97-4.58) P: 0.00, low birth weight (< 2500 g) (OR 6.95, 95% CI: 3-10.89) P: 0.00, an Appearance, Pulse, Grimace, Activity, Respiration (APGAR) score below 7 at the first minute (OR 7.56, 95% CI: 3.39-11.73) P: 0.00, preterm birth (OR 5.38, 95% CI: 3.23-7.5) P: 0.00, and neonates who were resuscitated at birth (OR 3.26, 95% CI: 1.96-4.56) P: 0.00. CONCLUSION The magnitude of neonatal sepsis in Africa remains high. This study identified several contributing factors, including prolonged rupture of membranes, a history of urinary tract or sexually transmitted infections, low birth weight (< 2500 g), an APGAR score below 7 at one minute, preterm birth, and resuscitation at birth. These findings underscore the importance of routinely screening for risk factors such as prolonged membrane rupture and maternal infections. Enhancing antenatal care, training providers in early neonatal sepsis management, and enforcing infection control measures.
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Affiliation(s)
- Endalk Birrie Wondifraw
- Department of Pediatric and Child Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia.
| | - Muluken Amare Wudu
- Department of Pediatric and Child Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Birhanu Desu Tefera
- Department of Emergency and Critical Care Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Kindu Yinges Wondie
- Department of Clinical Midwifery College of Medicine and Health Science, University, Gondar, Gondar, Ethiopia
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Sivathangam P, Srinivasamurthy D, Krishnamurthy V. Efficacy of Frozen Section Technique as a Rapid Diagnostic Tool in the Diagnosis of Funisitis in Premature Deliveries. Fetal Pediatr Pathol 2025; 44:106-113. [PMID: 39920564 DOI: 10.1080/15513815.2025.2457617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/10/2025] [Indexed: 02/09/2025]
Abstract
INTRODUCTION Presence of leucocytic infiltration in perivascular area or in Wharton jelly indicates funisitis. While conventional histopathological examination is the gold standard, its time delay hampers timely intervention. The frozen section technique offers a rapid alternative, enabling clinicians to promptly manage preterm early onset sepsis. METHODS This is a prospective study of 18 months. 125 preterms analyzed. Frozen sections and conventional sections of umbilical cord prepared and examined for inflammation by two researchers. Diagnostic accuracy of frozen sections versus conventional sections evaluated for sensitivity and specificity in detecting funisitis. RESULTS The frozen section of the umbilical cord was 85.5% sensitive and 86.7% specific in diagnosing funisitis. The inter-rater agreement for diagnosing funisitis was 72.2%. Funisitis on frozen section was 82.2% sensitive and 26.3% specific in diagnosing neonatal sepsis. CONCLUSION Frozen section examination of umbilical cord has good diagnostic ability in detecting funisitis. The inter-rater agreement is substantial.
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Affiliation(s)
- P Sivathangam
- Department of Pathology, JSS Hospital, JSS Academy of Higher Education and Research, Mysuru, India
| | - D Srinivasamurthy
- Department of Pathology, JSS Hospital, JSS Academy of Higher Education and Research, Mysuru, India
- Department of Pediatrics, JSS Hospital, JSS Academy of Higher Education and Research, Mysuru, India
| | - Vani Krishnamurthy
- Department of Pathology, JSS Hospital, JSS Academy of Higher Education and Research, Mysuru, India
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Gopal N, Chauhan N, Jain U, Dass SK, Chandra R. Nanomaterial Modified Screen Printed Electrode Based Electrochemical Genosensor for Efficient Detection of Neonatal Sepsis. Indian J Microbiol 2025; 65:515-528. [PMID: 40371025 PMCID: PMC12069212 DOI: 10.1007/s12088-024-01348-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 06/23/2024] [Indexed: 05/16/2025] Open
Abstract
The present work reports fabrication of nanomaterial based electrochemical genosensor for efficient detection of neonatal sepsis. For this purpose, virulent cfb gene of its major causative organisms, i.e. Group B Streptococcus (GBS) was selected. Further, a cfb specific 19-mer long amine terminated DNA probe was designed to be used as bioreceptor. The genosensing platform is fabricated by utilizing graphene oxide as nanomaterial which is deposited onto screen printed electrode (SPE) by electrophoretic deposition technique. Thereafter, the designed probe DNA is immobilized on graphene oxide modified SPE through EDC-NHS chemistry. Characterization of nanomaterial and fabricated genosensing platform is studied via X-ray diffraction, Scanning electron microscopy, atomic force microscopy, Fourier transmission infrared spectroscopy and cyclic voltammetry techniques. The fabricated genosensor (BSA/pDNA/GO/SPE) is able to efficiently detect target cfb gene with a linear detection range of 10-12-10-7 M, lower detection limit of 10-12 M and sensitivity of 725.9 µA M-1 cm-2. The biosensing ability of developed genosenor is also investigated in artificial serum sample and the obtained results are found within acceptable percentage relative standard deviation (%RSD), indicating its application in detecting neonatal sepsis in serum samples. Supplementary Information The online version contains supplementary material available at 10.1007/s12088-024-01348-w.
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Affiliation(s)
- Neha Gopal
- Drug Discovery and Development Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007 India
- Maharaja Surajmal Brij University, Bharatpur, Rajasthan 321201 India
| | - Nidhi Chauhan
- School of Health Sciences and Technology, UPES, Dehradun, Uttarakhand 248007 India
| | - Utkarsh Jain
- School of Health Sciences and Technology, UPES, Dehradun, Uttarakhand 248007 India
| | - Sujata K. Dass
- Department of Neurology, BLK Super Speciality Hospital, New Delhi, 110005 India
| | - Ramesh Chandra
- Drug Discovery and Development Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007 India
- Institute of Nano Medical Sciences, University of Delhi, Delhi, 110007 India
- Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007 India
- Maharaja Surajmal Brij University, Bharatpur, Rajasthan 321201 India
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18
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Ali MM, Kwatra G, Mengistu M, Kijineh B, Hailemeriam T, Worku E, Fenta DA, Lambiyo T, Reda DY, Alemayehu T. Trends of neonatal sepsis and its etiology at Hawassa, Ethiopia: a five year retrospective cross-sectional study. BMC Pediatr 2025; 25:152. [PMID: 40022032 PMCID: PMC11869412 DOI: 10.1186/s12887-025-05515-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 02/17/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND Neonatal sepsis is a significant cause of morbidity and mortality in low- income countries. Neonatal sepsis is classified as early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS). Etiologies responsible for EONS are mostly acquired vertically from the mother during or before birth with the possibility of prevention. The burden and etiology of neonatal sepsis is not uniform across the globe with huge disparities based on the income level of the countries. This study aimed to determine neonatal sepsis trends, prevalence, and etiologies at Hawassa University Comprehensive Specialised Hospital (HUCSH). METHODS A hospital-based retrospective cross-sectional study was conducted among newborns aged 0 to 90 days who were admitted to the HUCSH from January 2019 to July 2023. Patient-related information and the culture results were obtained from HUCSH microbiology laboratory registration book. Data analysis was performed using SPSS version 25 software. RESULTS Out of 2364 newborns suspected of having sepsis, 56% (95% CI: 54-58%) had culture-confirmed sepsis. When excluding Coagulase Negative Staphylococcus (CONS), the prevalence of culture-confirmed neonatal sepsis was 36.9%. The highest numbers of culture-confirmed cases was observed in 2021. The predominant bacteria identified were Coagulase Negative Staphylococcus (CONS) (34.1%), Klebsiella pneumoniae (12.9%), and Enterococcus (10.6%). Among culture-confirmed neonatal sepsis, 59.9% and 40.1% of cases were EONS and LONS, respectively. Coagulase Negative Staphylococcus and Enterococcus were the major bacteria found in both EONS and LONS while. Klebsiella pneumoniae was the second most common bacteria among newborns with EONS following CONS. CONCLUSIONS The prevalence of culture-confirmed neonatal sepsis was relatively high in the study area. Early-onset neonatal sepsis was consistently more prevalent than LONS. The predominant etiologies of neonatal sepsis excluding CONS were K. pneumoniae, Enterococcus, Enterobacter agglomerans, Acinetobacter species, and Staphylococcus aureus. Among newborns with EONS, the predominant bacteria were K. pneumoniae, Enterococcus, Enterobacter agglomerans, and Acinetobacter species.
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Affiliation(s)
- Musa Mohammed Ali
- School of Medical Laboratory Science, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia.
| | - Gaurav Kwatra
- Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
- South Africa Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa
- Department of Clinical Microbiology, Christian Medical College, Vellore, India
| | - Mulugeta Mengistu
- School of Medical Laboratory Science, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
| | - Biniyam Kijineh
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Wachemo University, Hosaina, Ethiopia
| | | | - Endale Worku
- Hawassa University Comprehensive Specialized Hospital, Hawassa, Ethiopia
| | - Demissie Assegu Fenta
- School of Medical Laboratory Science, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
| | - Tariku Lambiyo
- School of Medical Laboratory Science, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
| | - Dawit Yihdego Reda
- School of Medical Laboratory Science, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
| | - Tsegaye Alemayehu
- School of Medical Laboratory Science, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
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19
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Yuan J, Wu Y, Zhang Y, Zeng L, Zhou J, Piao M, Tong X, Wei Y, Cui L, Han T. Diagnostic Value of Umbilical Cord Blood Interleukin-6 Level in Premature Infants with Early-Onset Sepsis. CHILDREN (BASEL, SWITZERLAND) 2025; 12:301. [PMID: 40150583 PMCID: PMC11941668 DOI: 10.3390/children12030301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 02/25/2025] [Accepted: 02/26/2025] [Indexed: 03/29/2025]
Abstract
OBJECTIVE Early-onset sepsis (EOS) is a serious, grave, and frequently fatal condition in premature infants. This study aimed to assess the diagnostic value of interleukin-6 (IL-6) levels in umbilical cord blood for identifying EOS in preterm infants. METHODS This prospective cohort study was conducted on preterm infants between May 2019 and April 2021. Based on the diagnostic criteria for EOS, the participants were divided into EOS and non-EOS groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of cord blood IL-6 levels for EOS. RESULTS The levels of IL-6 were significantly higher in the EOS group (n = 10) compared to the non-EOS group (n = 178) [617.5 pg/mL (323.3, 1579.8) vs. 49.7 pg/mL (15.8, 142.8), respectively; p = 0.000]. ROC curve analysis demonstrated that a cutoff value of 250.5 pg/mL for cord blood IL-6 yielded a sensitivity of 90%, specificity of 82%, and area under the curve of 0.876, with a confidence interval of 0.753-0.999, indicating its high accuracy as a diagnostic marker for EOS among preterm infants (p < 0.001). CONCLUSIONS The detection of IL-6 in the umbilical cord blood offers convenience and exhibits significant diagnostic potential for EOS in preterm infants, thereby providing valuable support for clinical decision-making.
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Affiliation(s)
- Jinfang Yuan
- Department of Pediatric, Peking University Third Hospital, Beijing 100191, China; (J.Y.); (Y.Z.); (M.P.); (X.T.)
| | - Yufeng Wu
- Clinical Laboratory, Peking University Third Hospital, Beijing 100191, China; (Y.W.); (J.Z.); (L.C.)
| | - Yahui Zhang
- Department of Pediatric, Peking University Third Hospital, Beijing 100191, China; (J.Y.); (Y.Z.); (M.P.); (X.T.)
| | - Lin Zeng
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China;
| | - Jiansuo Zhou
- Clinical Laboratory, Peking University Third Hospital, Beijing 100191, China; (Y.W.); (J.Z.); (L.C.)
| | - Meihua Piao
- Department of Pediatric, Peking University Third Hospital, Beijing 100191, China; (J.Y.); (Y.Z.); (M.P.); (X.T.)
| | - Xiaomei Tong
- Department of Pediatric, Peking University Third Hospital, Beijing 100191, China; (J.Y.); (Y.Z.); (M.P.); (X.T.)
| | - Yuan Wei
- Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China;
| | - Liyan Cui
- Clinical Laboratory, Peking University Third Hospital, Beijing 100191, China; (Y.W.); (J.Z.); (L.C.)
| | - Tongyan Han
- Department of Pediatric, Peking University Third Hospital, Beijing 100191, China; (J.Y.); (Y.Z.); (M.P.); (X.T.)
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20
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Bader RS, Allabadi H, Ihsoun JM, Atout H, Khreishi RH, Bzour AM, Herzallah SA, Hamoudeh F, Sabbah R, Deareyyah NS, Zoughbi GG, Bakri RS, Shawar DH, Altorman SB, Najajra RH, Abu-Salah N, Marzouqa H, Hindiyeh M, Adwan R, Abu-Awwad M, Hamada S, Ayyad D, Atawna AA, Khammash H. Identification of bacterial pathogens and antimicrobial susceptibility of early-onset sepsis (EOS) among neonates in Palestinian hospitals: a retrospective observational study. BMC Pediatr 2025; 25:118. [PMID: 39955515 PMCID: PMC11830207 DOI: 10.1186/s12887-025-05470-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 01/28/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND Early-onset sepsis (EOS) remains a significant cause of morbidity and mortality in neonates worldwide, particularly in low-income countries. Identification of causative bacterial pathogens and assessment of their antimicrobial susceptibility are essential for guiding appropriate therapy and improving outcomes. The aim of this study was to determine the incidence, bacteriological profile and antibiotic susceptibility patterns of culture-positive EOS among a cohort of neonates in the Occupied Palestinian Territories (oPt). METHODS This retrospective observational study was conducted on neonates with proven positive blood cultures or positive cerebrospinal fluid (CSF) admitted to eight neonatal intensive care units (NICU) in the West Bank, oPt between January 2017 and December 2019. Data on microbiology laboratory blood cultures were retrieved from NICU registers and medical records were reviewed to obtain data on mothers and neonates. RESULTS Among the 95,319 neonates admitted to the eight NICUs during the study period, we detected 292 neonates with culture-proven EOS, resulting in an incidence rate of 3 per 1000 live births. The most common gram-positive bacteria identified among neonates were α hemolytic streptococcus (11.6%), CoNS (11.3%), and GBS (8.6%). E. coli (15.1%) and Klebsiella spp. (15.1%) were the most common gram-negative bacteria, followed by Acinetobacter (7.9%). Findings revealed gram-positive organisms were resistant to ciprofloxacin (57.1%) and highly sensitive to vancomycin (97.9%), meropenem (89.2%), amikacin (82.6%) and Piperacillin-Tazobactam (82.4%). Gram-negative organisms showed the highest antibiotic resistance to ampicillin (87.2%), cetofaxime, and highest sensitivity to meropenem (82.0%), Piperacillin-Tazobactam (70.7%), and amikacin (66.4%). CONCLUSION Our findings underscore the importance of continuous surveillance of bacterial pathogens and their antimicrobial susceptibility patterns in the management of EOS among neonates in Palestinian hospitals. The findings generated will guide clinicians in selecting appropriate empirical therapies and facilitating early and targeted interventions. Future research should focus on strategies to enhance infection prevention and control measures in Palestinian neonatal care unites to mitigate the burden of EOS and antimicrobial resistance.
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Affiliation(s)
- Raya S Bader
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
| | - Hala Allabadi
- Juzoor for Health and Social Development, Ramallah, Occupied Palestinian Territories.
- An-Najah National University, Nablus, Occupied Palestinian Territories.
| | | | - Hadeel Atout
- Palestine Medical Complex, Ramallah, Occupied Palestinian Territories
- AlQuds University, East Jerusalem, Occupied Palestinian Territories
| | - Reem H Khreishi
- Palestine Red Crescent Society (Jerusalem), East Jerusalem, Occupied Palestinian Territories
| | - Aseel M Bzour
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
| | - Shifaa A Herzallah
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
| | - Fidaa Hamoudeh
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
| | - Rana Sabbah
- Rafidia Hospital, Nablus, Occupied Palestinian Territories
| | | | - George G Zoughbi
- Holy Family Hospital, Bethlehem, Occupied Palestinian Territories
| | - Raneen S Bakri
- Caritas Baby Hospital, Bethlehem, Occupied Palestinian Territories
- Alia Hospital, Hebron, Occupied Palestinian Territories
| | - Deema H Shawar
- Palestine Red Crescent Society (Hebron), , Hebron, Occupied Palestinian Territories
| | - Safaa B Altorman
- Palestine Red Crescent Society (Hebron), , Hebron, Occupied Palestinian Territories
| | - Rajaa H Najajra
- Palestine Medical Complex, Ramallah, Occupied Palestinian Territories
| | - Nasser Abu-Salah
- Palestine Red Crescent Society (Jerusalem), East Jerusalem, Occupied Palestinian Territories
| | - Hiyam Marzouqa
- Caritas Baby Hospital, Bethlehem, Occupied Palestinian Territories
| | - Musa Hindiyeh
- Caritas Baby Hospital, Bethlehem, Occupied Palestinian Territories
| | - Rabee Adwan
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
- AlQuds University, East Jerusalem, Occupied Palestinian Territories
| | - Motee' Abu-Awwad
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
- AlQuds University, East Jerusalem, Occupied Palestinian Territories
| | - Sudqi Hamada
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
- AlQuds University, East Jerusalem, Occupied Palestinian Territories
| | - Dawood Ayyad
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
| | - Amir A Atawna
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories
- AlQuds University, East Jerusalem, Occupied Palestinian Territories
| | - Hatem Khammash
- Makassed Hospital, Ruba El-Adawiya Street, East Jerusalem, Occupied Palestinian Territories.
- AlQuds University, East Jerusalem, Occupied Palestinian Territories.
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21
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Shimeles G, Gedefie A, Motbainor H, Genet C. Vaginal colonization, vertical transmission rate, antimicrobial susceptibility profile, and associated factors of potential neonatal pathogens among pregnant women at public health facilities of Northeast Ethiopia. Front Public Health 2025; 13:1475357. [PMID: 39975790 PMCID: PMC11836021 DOI: 10.3389/fpubh.2025.1475357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 01/22/2025] [Indexed: 02/21/2025] Open
Abstract
Background Vaginal colonization by pathogenic bacteria increases the risk of bacterial infections such as sepsis, which is associated with high neonatal mortality. More than half a million newborn deaths occur globally each year due to infections that lead to sepsis. However, the problem is worsening in Ethiopia the evidence of vaginal colonization and vertical transmission is scarce. Methods A healthcare facility-based cross-sectional study was conducted in Dessie town from April 1 to June 30, 2023, among 348 pregnant women and their newborns. Socio-demographic, clinical, and related data were collected using a pre-tested semi-structured questionnaire. Vaginal swab samples from pregnant women and pooled external ear, nasal area, and umbilical swab samples from the newborns were collected and transported using Amies transport media. Samples were inoculated into blood agar, Todd Hewitt selective enrichment broth, and MacConkey agar for bacterial isolation, and Sabouraud Dextrose Agar and CHROM Agar for Candida species isolation. The antimicrobial susceptibility was performed on isolates using the Kirby-Bauer disc diffusion technique. Data was analyzed by SPSS version 25.0. Logistic regression model was used to identify the associated factors. Finally, variables with p < 0.05 and their 95% confidence interval were considered statistically significant. Results A total of 348 pregnant women attending vaginal delivery were included in the study. The maternal colonization and vertical transmission rates were 55.5% (193/348) and 53.9% (104/348), respectively. The most frequent potential pathogen among pregnant women was Escherichia coli (27.6%), followed by Candida spp. (14.1%), and Klebsiella spp. (6%). Similarly, the predominant isolates in the newborns were E. coli (16.4%), Candida spp. (6.3%), and Klebsiella spp. (3.6%). The overall multidrug resistance levels of potential pathogens were 37.3%. Living with domestic animals (p = 0.001), having premature rupture of membrane (p = 0.010) and history of urinary tract infection (p = 0.013) were significantly associated with maternal colonization. Potential pathogen colonization newborn was significantly associated with duration of labor (p = 0.024) and low birth weight (p < 0.001). Conclusion The finding of the present study revealed that vaginal colonization and vertical transmissions of potential pathogens and their antimicrobial resistance is still a significant problem. This alarms the urgency of evidence based-intervention to improve maternal and neonatal health.
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Affiliation(s)
- Getnet Shimeles
- Gishe Rabel Health Center, Debre Birhan, Ethiopia
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Alemu Gedefie
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Hilina Motbainor
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Chalachew Genet
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
- Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia
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22
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Lloyd LG, van Weissenbruch MM, Bekker A, Ferreyra C, Gleeson B, Dramowski A. Theoretical impact of a bedside decision-making tool on antibiotic use for suspected neonatal healthcare-associated infection: an observational study. BMC Pediatr 2025; 25:52. [PMID: 39838378 PMCID: PMC11749325 DOI: 10.1186/s12887-024-05323-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 12/11/2024] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Healthcare-associated infections (HAI) are a leading contributor to morbidity and mortality in hospitalised neonates. Diagnosing neonatal HAI is challenging owing to non-specific symptoms and lack of definitive diagnostic markers, contributing to high rates of inappropriate antibiotic use. This study evaluated the theoretical impact of implementing a bedside tool for decision-making on antibiotic length of therapy (LOT). METHODS This prospective observational physician-blinded study consecutively enrolled patients with suspected HAI events at a large South African neonatal unit from September 2022 to September 2023. The antibiotic decision-making tool included an infection prediction score (NeoHoP), and a point-of-care C-reactive protein test (CRP) performed at HAI diagnosis and 24 h later. The theoretical impact of the tool on antibiotic LOT was calculated. RESULTS We recruited 180 neonates with 214 episodes of suspected HAI, of which 22 (10.3%) were proven HAI, 56 (26.2%) were presumed HAI and 136 (63.6%) had HAI ruled out. The median observed antibiotic LOT was three days (9 days for proven HAI, 7 days for presumed HAI, and 3 days for no HAI). The antibiotic decision-making tool would theoretically reduce overall antibiotic LOT by 2 days (p < 0.001), particularly in neonates where HAI was subsequently excluded. CONCLUSION We developed an antibiotic decision-making tool to support the clinical evaluation of suspected neonatal HAI and demonstrated a significant potential impact on reducing antibiotic LOT. Given increasing antibiotic resistance rates globally, this tool should be further evaluated to minimise unnecessary antibiotic use in hospitalised neonates.
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Affiliation(s)
- Lizel Georgi Lloyd
- Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
| | | | - Adrie Bekker
- Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | | | | | - Angela Dramowski
- Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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Lee HY, Hsu YL, Lee WY, Huang KH, Tsai ML, Chen CL, Chang YC, Lin HC. Maternal Infections, Antibiotics, Steroid Use, and Diabetes Mellitus Increase Risk of Early-Onset Sepsis in Preterm Neonates: A Nationwide Population-Based Study. Pathogens 2025; 14:89. [PMID: 39861049 PMCID: PMC11769559 DOI: 10.3390/pathogens14010089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/04/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
The global evolution of pathogens causing early-onset sepsis (EOS), a critical condition in preterm infants, necessitates a re-evaluation of risk factors to develop updated prevention and treatment strategies. This nationwide case-control study in Taiwan analyzed data from the National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database from 2010 to 2019. The study included 176,681 mother-child pairs with preterm births. We identified 2942 clinical EOS cases from 5535 diagnosed sepsis cases, excluding unlikely cases. A control group of 14,710 preterm neonates without EOS was selected at a 1:5 ratio. Clinical EOS increased since 2017. Adjusted logistic regression identified significant EOS risk factors in preterm infants, including maternal fever, chorioamnionitis, maternal diabetes mellitus, maternal antibiotic usage, very preterm birth, birth weight (all with p < 0.001), maternal pneumonia (p = 0.002), and maternal CS (p = 0.004). Effective treatment of maternal conditions like diabetes, fever, and infections is essential to prevent EOS in preterm infants. Key measures include reducing unnecessary antibiotics or steroids, minimizing unnecessary cesarean sections, avoiding premature or prolonged rupture of membranes (PPROM), and increasing gestational age and neonatal birth weight. High-risk preterm neonates should be closely monitored for EOS and considered for antibiotics when warranted.
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Affiliation(s)
- Hao-Yuan Lee
- Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, No. 79-9, Sha-Luen-Hu, Xi-Zhou Li, Hou-Loung Town, Miaoli 35664, Taiwan
- Department of Pediatrics, Wei Gong Memorial Hospital, Miaoli 35159, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan
- Division of Pediatric Infectious Diseases, China Medical University Children’s Hospital, China Medical University, Taichung 40447, Taiwan;
| | - Yu-Lung Hsu
- Division of Pediatric Infectious Diseases, China Medical University Children’s Hospital, China Medical University, Taichung 40447, Taiwan;
| | - Wen-Yuan Lee
- Department of Neurosurgery, Wei Gong Memorial Hospital, Miaoli 35159, Taiwan;
- Department of Neurosurgery, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan
| | - Kuang-Hua Huang
- Department of Health Services Administration, China Medical University, Taichung 40447, Taiwan;
| | - Ming-Luen Tsai
- Division of Neonatology, China Medical University Children’s Hospital, China Medical University, Taichung 40447, Taiwan;
| | - Chyi-Liang Chen
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan;
| | - Yu-Chia Chang
- Department of Long Term Care, College of Health and Nursing, National Quemoy University, No. 1, University Road, Jinning Township, Kinmen County 892009, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung 41354, Taiwan
| | - Hung-Chih Lin
- Division of Neonatology, China Medical University Children’s Hospital, China Medical University, Taichung 40447, Taiwan;
- Department of Pediatrics, Asia University Hospital, Asia University, Taichung 41300, Taiwan
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24
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Nguyen TTB, Thi DAT, Truong QV, Pham TN. The diagnostic accuracy of umbilical cord procalcitonin in predicting early-onset neonatal infection. PLoS One 2025; 20:e0316987. [PMID: 39821188 PMCID: PMC11737792 DOI: 10.1371/journal.pone.0316987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 12/19/2024] [Indexed: 01/19/2025] Open
Abstract
INTRODUCTION To determine the threshold of umbilical cord blood procalcitonin for early-onset neonatal infection diagnosis. METHOD This prospective study was conducted on 126 neonates in the neonatal care unit of Hue University of Medicine and Pharmacy Hospital, Vietnam, from June 01, 2023 to August 31, 2024. All neonates showed signs at birth or risk factors for early-onset infection (EOI) and were divided into two groups: EOI group and non-EOI group. Umbilical cord blood samples were collected for procalcitonin analysis immediately after birth. RESULTS The median procalcitonin (PCT) levels in umbilical cord blood were significantly higher in the EOI group (0.154 ng/ml [0.092-0.197]) compared to the non-EOI group (0.097 ng/ml [0.082-0.134]; p < 0.001). Receiver operating characteristic (ROC) curve determined the optimal threshold value of PCT of 0.142 ng/ml with an AUC 0.751 (95% CI: 0.661-0.841, p<0.001) in the total population. At this cut-off, the Se, Sp, PPV, and NPV were 68.2%, 76.8%, 61.2%, and 81.8%, respectively. The optimal cut-off value for preterm neonates was 0.122 ng/ml (AUC: 0.785, 95% CI: 0.658-0.911, p<0.001) corresponding a Se of 79.2%, Sp of 74.1%, PPV of 73.1%, and NPV of 80.0%. In term group, the optimal cut-off value was 0.150 ng/ml (AUC: 0.726, 95% CI: 0.583-0.860, p<0.01), with a Se of 60.0%, Sp of 80.4%, PPV of 52.2%, and NPV of 84.9%. CONCLUSIONS Umbilical cord blood PCT concentration were elevated in neonates with EOI. PCT could be a valuable marker for the early diagnosis of EOI.
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Affiliation(s)
- Thi Thanh Binh Nguyen
- Department of Pediatrics, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam
- Faculty of Pediatrics, Hue University of Medicine and Pharmacy Hospital, Hue University, Hue City, Vietnam
| | - Diep Anh Truong Thi
- Department of Pediatrics, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam
| | - Quang Vinh Truong
- Department of Obstetrics & Gynecology, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam
| | - Thi Ny Pham
- Faculty of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital, Hue University, Hue City, Vietnam
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Ng D, Tran D, Subhi R, Fan WQ. Negative Healthcare Impacts of Management of Presumed Early-Onset Sepsis in Moderate to Late Preterm Infants on Feeding, Jaundice, and Hospital Length of Stay. Healthcare (Basel) 2025; 13:136. [PMID: 39857163 PMCID: PMC11765067 DOI: 10.3390/healthcare13020136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/31/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Early-onset sepsis in neonates is a potentially catastrophic condition that demands prompt management. However, laboratory diagnosis via cerebral spinal fluid and blood tests is often inconclusive, so diagnosis on the basis of clinical symptoms and risk factors is frequently required, and the majority of neonates treated with antibiotics for presumed early-onset sepsis (PEOS) do not have culture-proven sepsis. The management of such PEOS is mainly achieved via antibiotic therapy, which itself has adverse effects, creating a dilemma for clinicians in optimising healthcare. This study aimed to assess the impact of PEOS management on the common neonatal concerns of feeding tolerance, hyperbilirubinaemia, weight gain, and length of stay (LoS) in moderate to late preterm infants. METHODS A single-site, matched-cohort, retrospective study was performed on infants born between 32+3 and 36+6 weeks (2016 to 2019) admitted to the Neonatal Unit. PEOS infants on antibiotics (PEOS) were strictly matched by gestational age (±1 day) and birthweight (±5%) against a non-PEOS reference group (NPEOS). The key outcomes included the following: enteral feeding commencement and achievement; feeding intolerance (FI); phototherapy commencement and duration; antibiotic therapy duration; maximum bilirubin (MaxBili); LoS; and net postbirth weight gain. RESULTS There were no cases of culture-proven early-onset sepsis. PEOS (n = 185): NPEOS (n = 185) via multivariable analysis showed delayed enteral feed commencement (adjusted Odds Ratio [aOR]: 2.75; 95% confidence interval [CI]: 2.32, 3.27); there was no difference in FI, delayed onset of peak jaundice (aOR: 1.24; 95%CI: 1.12, 1.37), increased duration of phototherapy (aOR: 1.24; 95%CI: 1.10, 1.41), and increased LoS (aOR: 1.31; 95%CI; 1.02, 1.67). A univariate analysis also showed the following results (PEOS: NPEOS): no significant difference in MaxBili and delayed full enteral feed achievement (p = 0.010). Univariant or multivariable analysis showed no difference in irradiance levels. However, for NPEOS infants undergoing 0 or 1 phototherapy light treatment, there was an increased irradiance for PEOS (<0.001, 0.037, respectively). CONCLUSIONS In moderate to late preterm infants, while PEOS diagnosis and management resolve the negative health impacts of potential sepsis, they are associated with negative healthcare outcomes on feeding, jaundice, and hospital length of stay.
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Affiliation(s)
- Daniel Ng
- Department of Medicine, The Royal Melbourne Hospital, 300 Grattan St., Parkville, Melbourne, VIC 3050, Australia;
| | - David Tran
- Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Grattan St., Melbourne, VIC 3010, Australia; (D.T.); (R.S.)
- Neonatal Unit, Department of Paediatrics, Northern Health, 185 Cooper Street, Melbourne, VIC 3076, Australia
| | - Rami Subhi
- Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Grattan St., Melbourne, VIC 3010, Australia; (D.T.); (R.S.)
- Neonatal Unit, Department of Paediatrics, Northern Health, 185 Cooper Street, Melbourne, VIC 3076, Australia
| | - Wei Qi Fan
- Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Grattan St., Melbourne, VIC 3010, Australia; (D.T.); (R.S.)
- Neonatal Unit, Department of Paediatrics, Northern Health, 185 Cooper Street, Melbourne, VIC 3076, Australia
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Orfanos I, Krusell ET, Elfving K. Utility of interleukin-6 to identify serious bacterial infections in febrile infants aged ≤60 days. Acta Paediatr 2025; 114:173-179. [PMID: 39287096 PMCID: PMC11627453 DOI: 10.1111/apa.17422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 08/15/2024] [Accepted: 09/03/2024] [Indexed: 09/19/2024]
Abstract
AIM The aim of this study is to investigate the utility of interleukin-6 (IL-6) in the early diagnosis of serious bacterial infections (SBI) in febrile infants and to compare it with C-reactive protein (CRP). METHODS Retrospective study conducted in the paediatric emergency department in Gothenburg, Sweden, on previously healthy, full-term infants aged ≤60 days with fever without a source (FWS) from 2014 to 2017. RESULTS We included 536 infants with FWS, of whom IL-6 was analysed in 364 (68%) and CRP was analysed in 494 (92%). Approximately 70% of the infants presented with a fever duration of less than 12 h. The prevalence of SBIs was 14.8% (95% CI,11.3-18.9) in the IL-6 group and 17.8% (95% CI,14.5-21.5) in the CRP group. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of IL-6 ≥50 ng/L were 93%, 66%, 98% and 33%, respectively. For CRP ≥20 mg/L, the sensitivity, specificity, NPV, and PPV were 76%, 89%, 95%, and 55%, respectively. Logistic regression analysis showed that CRP was significantly associated with SBI (p < 0.0001) in the entire population, whereas IL-6 was not. CONCLUSION Interleukin-6 showed high sensitivity and NPV, which might assist in identifying SBIs early in febrile infants. However, IL-6 was not shown to be superior to CRP and further studies are needed to investigate whether IL-6 should be incorporated in clinical management.
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Affiliation(s)
- Ioannis Orfanos
- Department of Clinical SciencesLund UniversityLundSweden
- Department of PediatricsSkåne University HospitalLundSweden
| | | | - Kristina Elfving
- Department of PediatricsSahlgrenska University HospitalGothenburgSweden
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Pediatrics, Institute for Clinical Sciences, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
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Tisho AK, Mbugua PM, Bosire R, Karanja SM. Predictors of Length of Hospitalization for Neonatal Sepsis at Kenyatta Nation Hospital, Kenya: A Prospective Cross-Sectional Study. Health Sci Rep 2025; 8:e70344. [PMID: 39810921 PMCID: PMC11729743 DOI: 10.1002/hsr2.70344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 12/01/2024] [Accepted: 12/23/2024] [Indexed: 01/16/2025] Open
Abstract
Background and Aims Neonatal sepsis is a major cause of neonatal mortality worldwide. It remains a detrimental bottleneck to the WHO goal of eradicating preventable deaths for children below 5 years of age by 2030. Though the risk factors for adverse clinical outcomes for neonatal sepsis have been widely studied there is no universal consensus. Length of hospitalization is considered an indicator for adverse clinical outcome of neonatal sepsis. Markedly, literature is scarce regarding the drivers of extended hospitalization for neonatal sepsis in Kenya. Methodology This study determined the predictors of prolonged hospital stay for neonatal sepsis at the pediatric wards, KNH, Kenya. This was prospective cross-sectional research carried out among 314 mother/neonate pairs. The neonates were confirmed to have sepsis. Logistic regression analysis was conducted to determine maternal and neonate status predictive of duration of hospitalization. Results The median duration of hospital stay was 11 days and the majority (52.9%) were hospitalized for more than 11 days. The findings identified that maternal age ≥ 35 years (OR = 3.72, 95% CI: 1.61-8.59, p = 0.03), UTI during pregnancy (OR = 1.82, 95% CI: 1.07-3.11, p = 0.03), not breastfeeding (OR = 2.31, 95% CI: 1.29-4.14, p = 0.005), convulsion (OR = 2.03, 95% CI: 1.22-3.37, p = 0.01), jaundice (OR = 1.45, 95% CI: 1.10-1.91, p = 0.002), reduced movements (OR = 1.72, 95% CI: 1.08-2.72, p = 0.02), low birthweight (OR = 6.1, 95% CI: 2.48-14.99, p < 0.001) and preterm birth (OR = 3.1, 95% CI: 1.64-5.86, p < 0.001) were significant predictors of longer hospital stay. Conclusion The findings provide insights into the factors that can be monitored to predict the prognosis of neonatal sepsis. Besides, remedies can target these variables to mitigate prolonged hospitalization and severity of neonatal sepsis.
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Affiliation(s)
- Athman Khaltuma Tisho
- Paediatric WardKenyatta National HospitalNairobiKenya
- School of Public Health MedicineJomo Kenyatta University of Agriculture and TechnologyJujaKenya
| | | | - Rose Bosire
- Centre for Clinical ResearchKenya Medical Research InstituteNairobiKenya
| | - Simon Muturi Karanja
- School of Public Health MedicineJomo Kenyatta University of Agriculture and TechnologyJujaKenya
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28
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Pedersen MV, Renberg AFV, Christensen JK, Andersen HB, Andelius TCK, Kyng KJ, Andersen M, Henriksen TB. Lipopolysaccharide induced systemic inflammation and heart rate variability in a term newborn piglet model. Pediatr Res 2025; 97:138-144. [PMID: 39068272 PMCID: PMC11798847 DOI: 10.1038/s41390-024-03394-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 05/29/2024] [Accepted: 06/19/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Early biomarkers are needed to improve diagnosis and support antibiotic stewardship in neonatal sepsis. Heart rate variability (HRV) is proposed as such a biomarker. However, there is a lack of studies in term newborns. Infusion of lipopolysaccharide (LPS) from Escherichia coli induces systemic inflammation comparable to sepsis in newborns. We aimed to study the effect of systemic LPS induced inflammation on HRV in term newborn piglets. METHODS Baseline HRV was recorded for 1 h. This control period was compared to the hourly HRV for each piglet (n = 9) during 4 h of LPS infusion. For comparison, we used a mixed-effects regression model. RESULTS Systemic inflammation induced by LPS was found to reduce HRV. Compared to baseline, most measures of HRV decreased to lower values compared to baseline at 2 h, 3 h, and 4 h after initiation of LPS infusion. Heart rate (HR) was increased at 2 h, 3 h, and 4 h. When adjusting for HR in the mixed-effects regression model all reductions in HRV were explained by the increase in HR. CONCLUSIONS Reduced HRV may be an early biomarker of neonatal sepsis. However, an increase in HR alone could be an already available, more accessible, and interpretable biomarker of sepsis in term neonates. IMPACT In a term newborn piglet model, systemic inflammation induced by lipopolysaccharide from Escherichia coli reduced heart rate variability measures and increased heart rate. All reductions in heart rate variability were mediated by heart rate. While heart rate variability may be a biomarker of sepsis in term newborns, changes in heart rate alone could be a more readily available biomarker.
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Affiliation(s)
- Mette Vestergård Pedersen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
| | - Ann Frida Videbæk Renberg
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - Julie Kehlet Christensen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - Hannah Brogaard Andersen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - Ted Carl Kejlberg Andelius
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - Kasper Jacobsen Kyng
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - Mads Andersen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - Tine Brink Henriksen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
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29
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Boutouchent N, Vu TNA, Landraud L, Kennedy SP. Metagenome-assembled genomes of 72 Escherichia coli strains from vaginal samples collected from pregnant women. Microbiol Resour Announc 2024; 13:e0083124. [PMID: 39526797 PMCID: PMC11636315 DOI: 10.1128/mra.00831-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/15/2024] [Indexed: 11/16/2024] Open
Abstract
We report 72 metagenome-assembled genomes (MAGs) of Escherichia coli recovered from the vaginal microbiomes of pregnant women. The MAGs have an estimated median genome size of 5.1 Mb (IQR 4.9-5.3). The average number of unique genes identified per genome was 3,330 genes (IQR 3,356-3,501), with a mean of 1,708 per genome being annotated.
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Affiliation(s)
- Nassim Boutouchent
- Département de Biologie Computationnelle, Institut Pasteur, Université Paris Cité, Paris, France
- Département de Microbiologie, CHU de Rouen, Rouen, France
| | - Thi Ngoc Anh Vu
- VNU-Institute of Microbiology and Biotechnology, Vietnam National University, Hanoi, Vietnam
| | - Luce Landraud
- Université Paris Cité and Université Sorbonne Paris Nord, INSERM, IAME, Paris, France
| | - Sean P. Kennedy
- Département de Biologie Computationnelle, Institut Pasteur, Université Paris Cité, Paris, France
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30
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Peterson JL, Booth N, Mahaveer A. In or out: the experience and ethical issues encountered with an opt-out neonatal genetic study. BMJ Paediatr Open 2024; 8:e003107. [PMID: 39667954 DOI: 10.1136/bmjpo-2024-003107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024] Open
Affiliation(s)
- Jennifer Lh Peterson
- The University of Manchester Faculty of Biology Medicine and Health, Manchester, UK
- Neonatal Intensive Care Unit, Manchester University NHS Foundation Trust, Manchester, UK
| | - Nicola Booth
- Neonatal Intensive Care Unit, Manchester University NHS Foundation Trust, Manchester, UK
| | - Ajit Mahaveer
- Neonatal Intensive Care Unit, Manchester University NHS Foundation Trust, Manchester, UK
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31
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Bliss JM. Promise and pitfalls of umbilical cord blood culture for neonatal early-onset sepsis. Pediatr Res 2024; 96:1535-1536. [PMID: 38961168 DOI: 10.1038/s41390-024-03397-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 06/25/2024] [Indexed: 07/05/2024]
Affiliation(s)
- Joseph M Bliss
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
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32
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Hao Q, Chen J, Chen H, Zhang J, Du Y, Cheng X. Comparing nSOFA, CRIB-II, and SNAPPE-II for predicting mortality and short-term morbidities in preterm infants ≤32 weeks gestation. Ann Med 2024; 56:2426752. [PMID: 39520140 PMCID: PMC11552290 DOI: 10.1080/07853890.2024.2426752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 09/21/2024] [Accepted: 10/09/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Neonatal illness severity scores are not extensively studied for their ability to predict mortality or morbidity in preterm infants. The aim of this study was to compare the Neonatal Sequential Organ Failure Assessment (nSOFA), Clinical Risk Index for Babies-II (CRIB-II), and Score for Neonatal Acute Physiology with Perinatal extension-II (SNAPPE-II) for predicting mortality and short-term morbidities in preterm infants ≤32 weeks. METHODS In this retrospective study, infants born in 2017-2018 with gestational age (GA) ≤32 weeks were evaluated. nSOFA, CRIB-II, and SNAPPE-II scores were calculated for each patient, and the ability of these scores to predict mortality and morbidities was compared. The morbidities were categorized as mod/sev bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) requiring surgery, early-onset sepsis (EOS), late-onset sepsis (LOS), retinopathy of prematurity (ROP) requiring treatment, and severe intraventricular hemorrhage (IVH). Calculating the area under the curve (AUC) on receiver operating characteristic curves (ROC) analysis to predict and compare scoring systems' accuracy. RESULTS A total of 759 preterm infants were enrolled, of whom 88 deceased. The median nSOFA, CRIB-II, and SNAPPE-II scores were 2 (0, 3), 6 (4, 8), and 13 (5, 26), respectively. Compared with infants who survived, these three scores were significantly higher in those who deceased (p < 0.05). For predicting mortality, the AUC of the nSOFA, SNAPPE-II, and CRIB-II were 0.90, 0.82, and 0.79, respectively. The nSOFA scoring system had significantly higher AUC than CRIB-II and SNAPPE-II (p < 0.05). However, short-term morbidities were not strongly correlated with these three scoring systems. CONCLUSION In infants ≤32 weeks gestation, nSOFA scoring system is more valuable in predicting mortality than SNAPPE-II and CRIB-II. However, further studies are required to assess the predictive power of neonatal illness severity scores for morbidity.
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MESH Headings
- Humans
- Infant, Newborn
- Retrospective Studies
- Female
- Male
- Infant, Premature
- Gestational Age
- Organ Dysfunction Scores
- Bronchopulmonary Dysplasia/mortality
- Bronchopulmonary Dysplasia/epidemiology
- Infant, Premature, Diseases/mortality
- Infant, Premature, Diseases/diagnosis
- Infant, Premature, Diseases/epidemiology
- Retinopathy of Prematurity/mortality
- Retinopathy of Prematurity/diagnosis
- Retinopathy of Prematurity/epidemiology
- ROC Curve
- Severity of Illness Index
- Risk Assessment/methods
- Infant
- Enterocolitis, Necrotizing/mortality
- Enterocolitis, Necrotizing/epidemiology
- Enterocolitis, Necrotizing/diagnosis
- Infant Mortality
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Affiliation(s)
- Qingfei Hao
- Department of Neonatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jing Chen
- Department of Neonatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haoming Chen
- Department of Neonatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jing Zhang
- Department of Neonatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yanna Du
- Department of Neonatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiuyong Cheng
- Department of Neonatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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An AY, Acton E, Idoko OT, Shannon CP, Blimkie TM, Falsafi R, Wariri O, Imam A, Dibbasey T, Bennike TB, Smolen KK, Diray-Arce J, Ben-Othman R, Montante S, Angelidou A, Odumade OA, Martino D, Tebbutt SJ, Levy O, Steen H, Kollmann TR, Kampmann B, Hancock REW, Lee AH. Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation. EBioMedicine 2024; 110:105411. [PMID: 39472236 DOI: 10.1016/j.ebiom.2024.105411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 10/02/2024] [Accepted: 10/05/2024] [Indexed: 12/15/2024] Open
Abstract
BACKGROUND Neonatal sepsis is a deadly disease with non-specific clinical signs, delaying diagnosis and treatment. There remains a need for early biomarkers to facilitate timely intervention. Our objective was to identify neonatal sepsis gene expression biomarkers that could predict sepsis at birth, prior to clinical presentation. METHODS Among 720 initially healthy full-term neonates in two hospitals (The Gambia, West Africa), we identified 21 newborns who were later hospitalized for sepsis in the first 28 days of life, split into early-onset sepsis (EOS, onset ≤7 days of life) and late-onset sepsis (LOS, onset 8-28 days of life), 12 neonates later hospitalized for localized infection without evidence of systemic involvement, and 33 matched control neonates who remained healthy. RNA-seq was performed on peripheral blood collected at birth when all neonates were healthy and also within the first week of life to identify differentially expressed genes (DEGs). Machine learning methods (sPLS-DA, LASSO) identified genes expressed at birth that predicted onset of neonatal sepsis at a later time. FINDINGS Neonates who later developed EOS already had ∼1000 DEGs at birth when compared to control neonates or those who later developed a localized infection or LOS. Based on these DEGs, a 4-gene signature (HSPH1, BORA, NCAPG2, PRIM1) for predicting EOS at birth was developed (training AUC = 0.94, sensitivity = 0.93, specificity = 0.92) and validated in an external cohort (validation AUC = 0.72, sensitivity = 0.83, and specificity = 0.83). Additionally, during the first week of life, EOS disrupted expression of >1800 genes including those influencing immune and metabolic transitions observed in healthy controls. INTERPRETATION Despite appearing healthy at birth, neonates who later developed EOS already had distinct whole blood gene expression changes at birth, which enabled the development of a 4-gene predictive signature for EOS. This could facilitate early recognition and treatment of neonatal sepsis, potentially mitigating its long-term sequelae. FUNDING CIHR and NIH/NIAID.
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Affiliation(s)
- Andy Y An
- Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada
| | - Erica Acton
- Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada
| | - Olubukola T Idoko
- Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia; Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, United States; The Vaccine Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Casey P Shannon
- PROOF Centre of Excellence, Providence Research, Vancouver, Canada
| | - Travis M Blimkie
- Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada
| | - Reza Falsafi
- Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada
| | - Oghenebrume Wariri
- Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia; The Vaccine Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Abdulazeez Imam
- Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Tida Dibbasey
- Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Tue Bjerg Bennike
- Medical Microbiology and Immunology, Department of Health Science and Technology, Aalborg University, Gistrup, Denmark
| | - Kinga K Smolen
- Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, United States; Harvard Medical School, Boston, United States
| | - Joann Diray-Arce
- Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, United States; Harvard Medical School, Boston, United States
| | | | | | - Asimenia Angelidou
- Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, United States; Harvard Medical School, Boston, United States; Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, United States
| | - Oludare A Odumade
- Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, United States; Harvard Medical School, Boston, United States
| | - David Martino
- Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia
| | - Scott J Tebbutt
- PROOF Centre of Excellence, Providence Research, Vancouver, Canada; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, Canada
| | - Ofer Levy
- Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, United States; Harvard Medical School, Boston, United States; Broad Institute of MIT & Harvard, Cambridge, United States
| | - Hanno Steen
- Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, United States; Harvard Medical School, Boston, United States; Department of Pathology, Boston Children's Hospital, Boston, United States
| | - Tobias R Kollmann
- Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada; Telethon Kids Institute, Western Australia, Australia
| | - Beate Kampmann
- Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia; Institute for International Health, Charité Universitätsmedizin, Berlin, Germany
| | - Robert E W Hancock
- Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada
| | - Amy H Lee
- Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.
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Al Ghadeer HA, Alabdallah RH, AlKhalaf GI, Aldandan FK, Almohammed HA, Al Busaeed MM, Alkhawajah FM, Al Hassan KA, Alghadeer FA, Alreqa HH, Al Muaiweed RS, Al Bohassan AS, AlMuhaish AA, Alhabeeb AJ, Alsaif AK. Characteristics and Associated Risk Factors of Neonatal Sepsis: A Retrospective Study From Saudi Arabia. Cureus 2024; 16:e76517. [PMID: 39872571 PMCID: PMC11771527 DOI: 10.7759/cureus.76517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2024] [Indexed: 01/30/2025] Open
Abstract
Introduction Neonatal sepsis is defined as a systemic illness caused by bacteria, viruses, or fungi, characterized by hemodynamic abnormalities and clinical findings that result in morbidity and mortality. Neonatal morbidity and mortality are significantly influenced by neonatal sepsis. Causative pathogens and antimicrobial sensitivity profiles have changed over time, with significant geographic variation. Aim To determine the characteristics and associated risk factors of sepsis among neonates admitted into neonatal intensive care units (NICU) in Maternity and Children Hospital, AlAhsa, Saudi Arabia. Methodology An institution-based retrospective cross-sectional study was conducted among neonates who were admitted to the neonatal intensive care unit from January 2022 to December 2023 at the Maternity and Children Hospital, AlAhsa, Saudi Arabia. All neonates born with clinically diagnosed sepsis and positive culture were included in this study. Results This study included 134 neonates with a culture-proven diagnosis of neonatal sepsis during the study period. There were 23 (17.2%) cases of early-onset sepsis (EOS) and 111 (82.8%) cases of late-onset sepsis (LOS). Compared to late-onset sepsis (18.8%), Pseudomonas aeruginosa is more common in early-onset sepsis (33.3%). In cases of early-onset sepsis, Escherichia coli is isolated more often (33.3%) than in cases of late-onset (9.4%). Neonatal sepsis mortality is higher in LOS (25 [22.5%]) than in EOS (3 [13%]). Neonates with extremely preterm birth weight, gram-negative sepsis, and thrombocytopenia have a significantly higher mortality rate (p=<0.05). Conclusion In order to lower the risk among newborns, policymakers and/or managers will benefit from the information provided by the assessment of the prevalence, clinical outcomes, and risk factors for neonatal sepsis. Furthermore, developing hospital-based care strategies requires an understanding of the microorganisms that cause infections among neonates.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Anas K Alsaif
- Pharmacology, Ministry of National Guard, AlAhsa, SAU
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35
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Zou D, Li F, Jiao SL, Dong JR, Xiao YY, Yan XL, Li Y, Ren D. Infantile bacterial meningitis combined with sepsis caused by Streptococcus gallolyticus subspecies pasteurianus: A case report. World J Clin Cases 2024; 12:6472-6478. [PMID: 39507122 PMCID: PMC11438687 DOI: 10.12998/wjcc.v12.i31.6472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 08/14/2024] [Accepted: 08/21/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Streptococcus gallolyticus subspecies pasteurianus (SGSP) is a rare pathogen responsible for infant sepsis and meningitis and is potentially overlooked because it is not included in routine group B streptococcal screenings. Hence, we present a case of SGSP-induced infant meningitis and sepsis, accompanied by bronchopneumonia induced by multidrug-resistant Staphylococcus aureus (MRSA), providing insights into the identification, management, and prognosis of this bacterial infection. CASE SUMMARY A 45-day-old female infant presented with two episodes of high fever (maximum temperature: 39.5 °C) and two generalized grand mal seizure episodes that lasted over ten seconds and self-resolved without concomitant symptoms. Postadmission, the patient's C-reactive protein level was 40.73 mg/L, white blood cell count was 13.42 × 109/L, neutrophil ratio was 78.4%, procalcitonin level was 7.89 μg/L, cerebrospinal fluid (CSF) white cell count was 36 × 106/L, multinucleated cell ratio was 95.2%, and protein concentration was 0.41 g/L. Blood and CSF culture revealed that the pathogen was SGSP. The bacterium was sensitive to ampicillin, furazolidone, penicillin, lincomycin, moxifloxacin, rifampicin, vancomycin, and levofloxacin but resistant to clindamycin and tetracycline. Sputum culture revealed the presence of MRSA, which was sensitive to vancomycin. The patient was diagnosed with meningitis and sepsis caused by SGSP, accompanied by bronchopneumonia induced by MRSA. Ceftriaxone (100 mg/kg/d) combined with vancomycin (10 mg/kg/dose, q6h) was given as an anti-infective treatment postadmission. After 12 days of treatment, the infant was discharged from the hospital with normal CSF, blood culture, and routine blood test results, and no complications, such as subdural effusion, were observed on cranial computed tomography. No growth retardation or neurological sequelae occurred during follow-up. CONCLUSION SGPSP-induced infant bacterial meningitis and sepsis should be treated with prompt blood and CSF cultures, and a sensitive antibiotic therapy to ensure a favorable prognosis.
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Affiliation(s)
- Dan Zou
- Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Fen Li
- Department of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Shu-Li Jiao
- Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Jin-Rong Dong
- Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Yao-Yao Xiao
- Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Xiao-Ling Yan
- Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Yan Li
- Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Dan Ren
- Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
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Uberos J, Fernández-Marin E, Campos-Martínez A, Ruiz-López A, Luis García-Serrano J. Analysis of the Association between In Vitro Fertilization/Assisted Conception and the Development of Retinopathy of Prematurity in Very-Low-Birth Weight Newborns. Turk Arch Pediatr 2024; 59:547-552. [PMID: 39540751 PMCID: PMC11562287 DOI: 10.5152/turkarchpediatr.2024.24157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 08/19/2024] [Indexed: 11/16/2024]
Abstract
Objective The objective is to study to what extent the development of retinopathy of prematurity (ROP) is associated with assisted conception (AC) and in vitro fertilization (IVF) in a tertiary referral hospital. Materials and Methods This study is a retrospective observational cohort study. Very-low-birth weight (VLBW) infants with gestational age (GA) <32 weeks or birth weight <1500 g were admitted to the neonatal unit of a tertiary care hospital between January 1, 2011, and December 31, 2021. The study determined the degree of ROP developed according to the type of fertilization used for conception. Main outcome measures were ROP prevalence in pregnancies obtained after IVF/intracytoplasmic sperm injection (ICSI) in the period from January 1, 2011, to December 31, 2021, in a tertiary hospital. Results Of the 408 infants included in the study sample, 105 (25.7%) were born following AC and 12.4% of these developed ROP. In our sample, the practice of IVF was not associated with an increase in the incidence of VLBW infants (R2 = 0.12; P = .29). Conclusion Conception achieved via AC or IVF is not significantly associated with ROP in any degree of severity.
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Affiliation(s)
- Jose Uberos
- Neonatal Intensive Care Unit, San Cecilio Clinical Hospital, School of Medicine, Granada, Spain
| | | | - Ana Campos-Martínez
- Neonatal Intensive Care Unit, San Cecilio Clinical Hospital, School of Medicine, Granada, Spain
| | - Aida Ruiz-López
- Neonatal Intensive Care Unit, San Cecilio Clinical Hospital, School of Medicine, Granada, Spain
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Price AD, Becker ER, Barrios EL, Mazer MB, McGonagill PW, Bergmann CB, Goodman MD, Gould RW, Rao M, Polcz VE, Kucaba TA, Walton AH, Miles S, Xu J, Liang M, Loftus TJ, Efron PA, Remy KE, Brakenridge SC, Badovinac VP, Griffith TS, Moldawer LL, Hotchkiss RS, Caldwell CC. Surviving septic patients endotyped with a functional assay demonstrate active immune responses. Front Immunol 2024; 15:1418613. [PMID: 39469706 PMCID: PMC11513262 DOI: 10.3389/fimmu.2024.1418613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 09/24/2024] [Indexed: 10/30/2024] Open
Abstract
Introduction Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients. Methods This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an 'immunocompetent', 'immunosuppressed endotype', and two 'mixed' endotypes. Results Whole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. 'Immunocompetent' endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the 'immunosuppressed' endotype. Similarly, 'immunocompetent' endotype patients on day 4 had a higher in-hospital survival compared to the 'immunosuppressed' endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality. Conclusions Increased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early 'immunocompetent' endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.
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Affiliation(s)
- Adam D. Price
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Ellen R. Becker
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Evan L. Barrios
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Monty B. Mazer
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Patrick W. McGonagill
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Christian B. Bergmann
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Michael D. Goodman
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Robert W. Gould
- Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Mahil Rao
- Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Valerie E. Polcz
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Tamara A. Kucaba
- Department of Urology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Andrew H. Walton
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Sydney Miles
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Julie Xu
- Department of Urology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Muxuan Liang
- Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL, United States
| | - Tyler J. Loftus
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Philip A. Efron
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Kenneth E. Remy
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Scott C. Brakenridge
- Department of Surgery, Harborview Medical Center, University of Washington School of Medicine, Seattle, WA, United States
| | - Vladimir P. Badovinac
- Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
- Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Thomas S. Griffith
- Department of Urology, University of Minnesota Medical School, Minneapolis, MN, United States
- Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, United States
- Minneapolis VA Healthcare System, Minneapolis, MN, United States
| | - Lyle L. Moldawer
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Richard S. Hotchkiss
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Charles C. Caldwell
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
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Tądel K, Dudek A, Bil-Lula I. AI Algorithms for Modeling the Risk, Progression, and Treatment of Sepsis, Including Early-Onset Sepsis-A Systematic Review. J Clin Med 2024; 13:5959. [PMID: 39408019 PMCID: PMC11478112 DOI: 10.3390/jcm13195959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/17/2024] [Accepted: 10/03/2024] [Indexed: 10/20/2024] Open
Abstract
Sepsis remains a significant contributor to neonatal mortality worldwide. However, the nonspecific nature of sepsis symptoms in neonates often leads to the necessity of empirical treatment, placing a burden of ineffective treatment on patients. Furthermore, the global challenge of antimicrobial resistance is exacerbating the situation. Artificial intelligence (AI) is transforming medical practice and in hospital settings. AI shows great potential for assessing sepsis risk and devising optimal treatment strategies. Background/Objectives: This review aims to investigate the application of AI in the detection and management of neonatal sepsis. Methods: A systematic literature review (SLR) evaluating AI methods in modeling and classifying sepsis between 1 January 2014, and 1 January 2024, was conducted. PubMed, Scopus, Cochrane, and Web of Science were systematically searched for English-language studies focusing on neonatal sepsis. Results: The analyzed studies predominantly utilized retrospective electronic medical record (EMR) data to develop, validate, and test AI models to predict sepsis occurrence and relevant parameters. Key predictors included low gestational age, low birth weight, high results of C-reactive protein and white blood cell counts, and tachycardia and respiratory failure. Machine learning models such as logistic regression, random forest, K-nearest neighbor (KNN), support vector machine (SVM), and XGBoost demonstrated effectiveness in this context. Conclusions: The summarized results of this review highlight the great promise of AI as a clinical decision support system for diagnostics, risk assessment, and personalized therapy selection in managing neonatal sepsis.
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Affiliation(s)
- Karolina Tądel
- Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, 211 Borowska Street, 50-556 Wroclaw, Poland;
- Institute of Mother and Child, 17a Kasprzaka Street, 01-211 Warsaw, Poland
| | - Andrzej Dudek
- Department of Econometrics and Informatics, Faculty of Economics and Finance, Wroclaw University of Economics, Nowowiejska Street, 58-500 Jelenia Góra, Poland;
| | - Iwona Bil-Lula
- Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, 211 Borowska Street, 50-556 Wroclaw, Poland;
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Lemma K, Berhane Y. Early onset neonatal sepsis and its associatited factors: a cross sectional study. BMC Pregnancy Childbirth 2024; 24:617. [PMID: 39342103 PMCID: PMC11438148 DOI: 10.1186/s12884-024-06820-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 09/11/2024] [Indexed: 10/01/2024] Open
Abstract
BACKGROUND Sepsis is the 3rd leading cause of neonatal mortality in Ethiopia contributing to 16% of neonatal death. In a hospital study, neonatal sepsis was the leading diagnosis at admission and the second leading cause of neonatal death at the neonatal intensive care unit. Among other factors repeated vaginal examination during labor is known to contribute to sepsis in low-income settings. However, there is limited evidence in the Ethiopian setting. OBJECTIVE The objective of this study was to examine the association between early-onset neonatal sepsis and repeated vaginal examinations. METHODS The study was conducted at Gandhi Memorial Hospital, a public maternity and newborn care hospital. We followed 672 mother-newborn pairs by phone until 7 days of age to detect clinical sepsis. Data were analyzed using SPSS version 20 software. Adjusted odds ratio risk (AOR) with a corresponding 95% confidence interval (CI) was used to show the strength of associations and variables with p-value < 0.05 were considered to be statistically significant. RESULTS The incidence of early-onset neonatal sepsis was found to be 20.83% (95% CI 17.60, 24.00). Having a frequent vaginal examination (four or more times) during labor and delivery, prolonged rupture of membranes, induced labor and gestational age < 37 weeks were strongly associated with the development of early-onset neonatal sepsis, (AOR 2. 69;95 CI: 1.08, 6.70) AOR 5.12(95% CI 1.31, 20.00), AOR of 5.24 (95% CI 1.72, AOR4.34 (95% CI 1.20, 15.68), 16.00), respectively. CONCLUSION Frequent digital vaginal examination prolonged rupture of membranes, induced labor and gestational age < 37 weeks significantly increases the risk of early onset neonatal sepsis. We also recommend further study using neonatal blood culture to better diagnose early onset neonatal sepsis objectively.
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Affiliation(s)
- Ketsela Lemma
- Department of Obstetrics and Gynecology Gandhi Memorial Hospital, Addis Ababa, Ethiopia.
| | - Yemane Berhane
- Addis Continental Institute of Public Health, Addis Ababa, Ethiopia
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40
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Raturi A, Chandran S. Neonatal Sepsis: Aetiology, Pathophysiology, Diagnostic Advances and Management Strategies. Clin Med Insights Pediatr 2024; 18:11795565241281337. [PMID: 39371316 PMCID: PMC11452898 DOI: 10.1177/11795565241281337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 08/21/2024] [Indexed: 10/08/2024] Open
Abstract
Neonatal sepsis, a bloodstream infection in the first 28 days of life, is a leading cause of morbidity and mortality among infants in both developing and developed countries. Additionally, sepsis is distinguished in neonates by unique pathophysiological and presentational factors relating to its development in immature neonatal immune systems. This review focuses on the current understanding of the mechanics and implications of neonatal sepsis, providing a comprehensive overview of the epidemiology, aetiology, pathophysiology, major risk factors, signs and symptoms and recent consensus on the diagnosis and management of both early-onset and late-onset neonatal sepsis. It also includes a discussion on novel biomarkers and upcoming treatment strategies for the condition as well as the potential of COVID-19 infection to progress to sepsis in infants.
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Affiliation(s)
- Adi Raturi
- University of Glasgow School of Medicine, Glasgow, UK
| | - Suresh Chandran
- Department of Neonatology, KK Women’s and Children’s Hospital, Singapore, Singapore
- Duke NUS Medical School, Singapore, Singapore
- Lee Kong Chian School of Medicine, Singapore, Singapore
- Yong Loo Lin School of Medicine, Singapore, Singapore
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Ling J, Hryckowian AJ. Re-framing the importance of Group B Streptococcus as a gut-resident pathobiont. Infect Immun 2024; 92:e0047823. [PMID: 38436256 PMCID: PMC11392526 DOI: 10.1128/iai.00478-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2024] Open
Abstract
Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial species that causes disease in humans across the lifespan. While antibiotics are used to mitigate GBS infections, it is evident that antibiotics disrupt human microbiomes (which can predispose people to other diseases later in life), and antibiotic resistance in GBS is on the rise. Taken together, these unintended negative impacts of antibiotics highlight the need for precision approaches for minimizing GBS disease. One possible approach involves selectively depleting GBS in its commensal niches before it can cause disease at other body sites or be transmitted to at-risk individuals. One understudied commensal niche of GBS is the adult gastrointestinal (GI) tract, which may predispose colonization at other body sites in individuals at risk for GBS disease. However, a better understanding of the host-, microbiome-, and GBS-determined variables that dictate GBS GI carriage is needed before precise GI decolonization approaches can be developed. In this review, we synthesize current knowledge of the diverse body sites occupied by GBS as a pathogen and as a commensal. We summarize key molecular factors GBS utilizes to colonize different host-associated niches to inform future efforts to study GBS in the GI tract. We also discuss other GI commensals that are pathogenic in other body sites to emphasize the broader utility of precise de-colonization approaches for mitigating infections by GBS and other bacterial pathogens. Finally, we highlight how GBS treatments could be improved with a more holistic understanding of GBS enabled by continued GI-focused study.
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Affiliation(s)
- Joie Ling
- Department of
Medicine, Division of Gastroenterology and Hepatology, University of
Wisconsin School of Medicine and Public
Health, Madison,
Wisconsin, USA
- Department of Medical
Microbiology and Immunology, University of Wisconsin School of Medicine
and Public Healthon,
Madison, Wisconsin, USA
- Microbiology Doctoral
Training Program, University of
Wisconsin-Madison, Madison,
Wisconsin, USA
| | - Andrew J. Hryckowian
- Department of
Medicine, Division of Gastroenterology and Hepatology, University of
Wisconsin School of Medicine and Public
Health, Madison,
Wisconsin, USA
- Department of Medical
Microbiology and Immunology, University of Wisconsin School of Medicine
and Public Healthon,
Madison, Wisconsin, USA
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42
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Teacoe DA, Cormoș RC, Toma DA, Ștef L, Cucerea M, Muțiu I, Chicea R, Popescu D, Chicea ED, Boicean AG, Galiș R, Ognean ML. Congenital Sepsis with Candida albicans-A Rare Event in the Neonatal Period: Report of Two Cases and Literature Review. Microorganisms 2024; 12:1869. [PMID: 39338543 PMCID: PMC11433654 DOI: 10.3390/microorganisms12091869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Candida spp. is rarely found in neonatal early-onset sepsis (EOS) etiology. However, candidemia is associated with increased mortality and morbidity, as in late-onset sepsis. Congenital candidiasis may present as a mucocutaneous infection or, more rarely, as a systemic infection in term and preterm infants. This paper presents case reports of two cases of congenital systemic candidiasis (CSC) caused by Candida albicans and a review of the data in the literature. An electronic search of PubMed, Scopus, and Google Scholar was performed to identify publications on congenital candidiasis. Both neonates were male, born vaginally, with risk factors for congenital candidiasis. One of the infants was born at term and presented with an almost generalized maculopapular rash at birth and congenital candidemia; parenteral fluconazole was used successfully. The other infant was born prematurely at 28 weeks of gestation; blood culture, gastric aspirate, and maternal vaginal cultures sampled at birth were positive for C. albicans. Liver and kidney involvement became apparent on the third day of life, while lung involvement was clinically evident on the fourth day. Prolonged parenteral fluconazole was administered due to multiple organ involvement and persistent candidemia. Our experience with the presented cases, similar to data in the literature, suggests that CSC may occur at any gestational age, with various clinical pictures, sometimes mimicking bacterial sepsis, and even in the absence of the rash. Careful anamnesis and a high index of suspicion are important for the prompt recognition and treatment of CSC, optimizing the short- and long-term outcomes. Further research should focus on CSC to improve its diagnosis.
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Affiliation(s)
- Dumitru Alin Teacoe
- Faculty of Medicine, Lucian Blaga University Sibiu, 550169 Sibiu, Romania
- Clinical County Emergency Hospital Sibiu, 550245 Sibiu, Romania
| | | | | | - Laura Ștef
- Faculty of Medicine, Lucian Blaga University Sibiu, 550169 Sibiu, Romania
- Clinical County Emergency Hospital Sibiu, 550245 Sibiu, Romania
| | - Manuela Cucerea
- Department of Neonatology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology, 540142 Targu Mures, Romania
| | | | - Radu Chicea
- Faculty of Medicine, Lucian Blaga University Sibiu, 550169 Sibiu, Romania
- Clinical County Emergency Hospital Sibiu, 550245 Sibiu, Romania
| | - Dragoș Popescu
- Faculty of Medicine, Lucian Blaga University Sibiu, 550169 Sibiu, Romania
- Clinical County Emergency Hospital Sibiu, 550245 Sibiu, Romania
| | | | - Adrian Gheorghe Boicean
- Faculty of Medicine, Lucian Blaga University Sibiu, 550169 Sibiu, Romania
- Clinical County Emergency Hospital Sibiu, 550245 Sibiu, Romania
| | - Radu Galiș
- Department of Neonatology, Clinical County Emergency Hospital Bihor, 410167 Oradea, Romania
- Doctoral School, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Maria Livia Ognean
- Faculty of Medicine, Lucian Blaga University Sibiu, 550169 Sibiu, Romania
- Clinical County Emergency Hospital Sibiu, 550245 Sibiu, Romania
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Groen J, van der Kuip M, Budding D, Bos MP, Benninga MA, Niemarkt HJ, de Meij TGJ. Assessing Diagnostic Performance of Molecular Culture for Neonatal Sepsis: Protocol of the CHAMPIONS Study. Diagnostics (Basel) 2024; 14:1930. [PMID: 39272715 PMCID: PMC11394283 DOI: 10.3390/diagnostics14171930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/26/2024] [Accepted: 08/29/2024] [Indexed: 09/15/2024] Open
Abstract
Managing neonatal sepsis is challenging due to nonspecific clinical signs, hematological markers with poor accuracy, and a lengthy turnaround time for the identification of microorganisms. Delaying the initiation of antibiotics in truly infected infants can lead to severe morbidity and mortality. Therefore, decisions regarding empiric antibiotic treatment are risk stratified, which exposes many uninfected infants to antibiotics. This causes gut microbiota perturbation, unnecessary hospital admissions, and the generation of multi-resistant organisms. High-speed diagnostic assays could expedite discontinuation or avert the initiation of antibiotics in uninfected infants. This study will evaluate the diagnostic performance of molecular culture (MC), a rapid broad-range PCR-based bacterial profiling technique, for diagnosing neonatal sepsis in infants below 90 days old. A multi-center prospective observational cohort study will include infants evaluated for early and late-onset sepsis. Routine evaluation for suspected sepsis includes microbiological cultures of blood. Additionally, blood for MC will be collected. For early-onset sepsis, umbilical cord blood may be used alternatively. Primary outcome is the agreement between MC and conventional blood culture results. Secondary outcome is the agreement of both assays with clinical sepsis using four different, commonly used definitions. Faster diagnostic pathways for sepsis may reduce antibiotic exposure time. Broad-range molecular assays may identify pathogens undetectable by conventional methods. Employment of umbilical cord blood samples for early-onset sepsis diagnosis can resolve challenges in collecting adequate blood volume and could further expedite treatment decisions.
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Affiliation(s)
- Jip Groen
- Department of Pediatric Gastroenterology, Amsterdam University Medical Center,1105 AZ Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Research Institute, 1105 AZ Amsterdam, The Netherlands
- Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Martijn van der Kuip
- Department of Pediatric Infectious Diseases, Rheumatology and Immunology, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
| | | | | | - Marc A Benninga
- Department of Pediatric Gastroenterology, Amsterdam University Medical Center,1105 AZ Amsterdam, The Netherlands
| | - Hendrik J Niemarkt
- Maxima Medical Center, Department of Neonatology, 5504 DB Veldhoven, The Netherlands
| | - Tim G J de Meij
- Department of Pediatric Gastroenterology, Amsterdam University Medical Center,1105 AZ Amsterdam, The Netherlands
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Powell J, Beirne I, Minihan B, O’Connell NH, Sharma S, Dunworth M, Philip RK, Dunne CP. Neonatal bacteraemia in Ireland: A ten-year single-institution retrospective review. PLoS One 2024; 19:e0306855. [PMID: 39178209 PMCID: PMC11343407 DOI: 10.1371/journal.pone.0306855] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 06/25/2024] [Indexed: 08/25/2024] Open
Abstract
Neonatal sepsis is a catastrophic condition of global concern, with reported mortality rates exceeding 10%. Bloodstream infections are an important cause of sepsis, and epidemiological studies of these infections are crucial for predicting the most common aetiological agents and antimicrobial susceptibility patterns and for developing antimicrobial guidelines. For the ten-year study period from July 2013 to June 2023, all neonatal bacteraemia cases were reviewed prospectively using an enhanced surveillance protocol. The patients were stratified according to their age at the time of blood culture collection: early onset if diagnosed in the first 72 hours of life, and late onset if diagnosed after that time. During the study period, 170 blood cultures were positive from 144 patients, of which 89 specimens from 64 patients represented the growth of significant pathogens. Coagulase-negative staphylococci (CoNS) were the most common pathogens identified (52%, 33/64), followed by Escherichia coli (14%, 9/64), Group B Streptococcus (GBS: 11%, 7/64) and Staphylococcus aureus (11%, 7/64). GBS was more commonly identified in early onset patients, while CoNS were predominantly associated with late onset. The presence of an intravascular catheter, maternal urinary tract infections and the receipt of total parenteral nutrition or transfused blood were identified as significant risk factors. The fatality rate was 8% (5/64). in summary, this study provides a detailed overview of the epidemiology of neonatal bacteraemia in a large teaching hospital in the Midwest of Ireland over a decade.
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Affiliation(s)
- James Powell
- Department of Microbiology, University Hospital Limerick, Limerick, Ireland
- School of Medicine and Centre for Interventions in Infection, Inflammation and Immunity (4i), University of Limerick, Limerick, Ireland
| | - Irene Beirne
- Department of Paediatrics, Division of Neonatology, University Maternity Hospital Limerick, Limerick, Ireland
| | - Brid Minihan
- Department of Microbiology, University Hospital Limerick, Limerick, Ireland
| | - Nuala H. O’Connell
- Department of Microbiology, University Hospital Limerick, Limerick, Ireland
- School of Medicine and Centre for Interventions in Infection, Inflammation and Immunity (4i), University of Limerick, Limerick, Ireland
| | - Santosh Sharma
- School of Medicine and Centre for Interventions in Infection, Inflammation and Immunity (4i), University of Limerick, Limerick, Ireland
| | - Margo Dunworth
- Department of Paediatrics, Division of Neonatology, University Maternity Hospital Limerick, Limerick, Ireland
| | - Roy K. Philip
- Department of Paediatrics, Division of Neonatology, University Maternity Hospital Limerick, Limerick, Ireland
- University of Limerick School of Medicine, Limerick, Ireland
| | - Colum P. Dunne
- School of Medicine and Centre for Interventions in Infection, Inflammation and Immunity (4i), University of Limerick, Limerick, Ireland
- School of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland
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45
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Ferorelli D, Goffredo VM, Graziano E, Mastrapasqua M, Telegrafo M, Vinci A, Visci P, Benevento M, Zotti F, Foglianese A, Panza R, Solarino B, Dell’Erba A, Laforgia N. Quality improvement in neonatal care through enhanced patient safety and clinical risk management: a before-and-after study about neonatal sepsis. Front Med (Lausanne) 2024; 11:1430853. [PMID: 39228806 PMCID: PMC11370662 DOI: 10.3389/fmed.2024.1430853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 07/12/2024] [Indexed: 09/05/2024] Open
Abstract
Introduction Neonatal sepsis, classified into early-onset and late-onset based on symptom timing, poses significant risks of morbidity and mortality, especially in low birth weight infants. Effective clinical risk management protocols are crucial in reducing these risks. Methods This before-and-after study evaluated the impact of a newly implemented clinical risk management protocol in the Neonatology and Neonatal Intensive Care Unit (NICU) at Policlinico Hospital-University of Bari. The study included 399 neonates over three years, comparing pre- and post-protocol outcomes. Data collection focused on maternal and neonatal demographics, infection rates, and hospital stay lengths. Statistical analysis included t-tests, Wilcoxon-Mann-Whitney tests, and logistic regression models. Results The study found no significant differences in neonatal pathologies or demographics between pre- and post-protocol groups. However, post-protocol implementation showed a notable reduction in umbilical venous catheter (UVC) infections (p = 0.018) and improved hospital stay lengths. Blood and urine cultures did not show significant changes in microbial patterns post-protocol. Discussion The findings underscore the effectiveness of structured clinical risk management protocols in enhancing neonatal outcomes, particularly in reducing specific infection risks. Despite the study's limitations, including its observational nature and sample size, the results advocate for broader adoption and further research on these protocols in diverse healthcare settings. The positive outcomes highlight the importance of continuous clinical risk management efforts in high-risk neonatal environments.
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Affiliation(s)
- Davide Ferorelli
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Vito Maria Goffredo
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Elena Graziano
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Maurizio Mastrapasqua
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Michele Telegrafo
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Annachiara Vinci
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Paolo Visci
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Marcello Benevento
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Fiorenza Zotti
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Alessandra Foglianese
- Department of Interdisciplinary Medicine, Section of Neonatology and Neonatal Intensive Care Unit, University of Bari “A. Moro”, Bari, Italy
| | - Raffaella Panza
- Department of Interdisciplinary Medicine, Section of Neonatology and Neonatal Intensive Care Unit, University of Bari “A. Moro”, Bari, Italy
| | - Biagio Solarino
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Alessandro Dell’Erba
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
| | - Nicola Laforgia
- Interdisciplinary Department of Medicine (DIM), Section of Legal Medicine, University of Bari “Aldo Moro”, Bari, Italy
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Tran NTH, Tran LC, Tran DL, Nguyen VT, Le MH, Nguyen NTK. Utilizing Predictive Factors as a Screening Tool for Early-Onset Sepsis in Neonates. Cureus 2024; 16:e66312. [PMID: 39238695 PMCID: PMC11376967 DOI: 10.7759/cureus.66312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2024] [Indexed: 09/07/2024] Open
Abstract
INTRODUCTION Neonatal early-onset sepsis (EOS) is a severe condition that affects newborns within the first three days of life, with high mortality rates, particularly in low- and middle-income countries (LMICs). In Vietnam, the diagnosis and management of EOS are challenged by ambiguous clinical signs and limited access to blood culture testing facilities. Early identification of at-risk neonates using a predictive risk factor model is crucial for improving neonatal care and reducing mortality. OBJECTIVES This study aims to identify maternal and neonatal risk factors associated with EOS and develop a predictive screening tool to facilitate the early detection of at-risk neonates in Vietnam. MATERIALS AND METHODS A nested case-control study was conducted on 225 neonates at the central neonatal unit in a principal tertiary hospital in southwestern Vietnam over a two-year period. Risk factors were identified using univariable and multivariable logistic regression analyses. A predictive nomogram was developed and evaluated for discrimination, calibration, and decision curve analysis (DCA). RESULTS The study identified eight significant risk factors for EOS, including maternal genital infections during the third trimester, urinary tract infections (UTIs) during pregnancy, hypertension during pregnancy, insufficient maternal weight gain, rupture of membranes (ROM) ≥18 hours, meconium-stained amniotic fluid, first-minute APGAR score <7, and preterm birth <34 weeks. The predictive model demonstrated excellent discrimination with an area under the curve (AUC) of 0.913 (95% CI: 0.876-0.95, p<0.001) and good calibration (Hosmer-Lemeshow test with χ²(df)=5.496 (5), p=0.358). The model-based nomogram showed high sensitivity (82.7%) and specificity (83.3%) at an optimal cutoff of 0.25. The DCA illustrates the model's good clinical utility, providing a higher net benefit across most threshold probability ranges (0.0-0.96). CONCLUSIONS This study presents a robust predictive model for the early identification of neonates at risk of EOS in Vietnam, based on key maternal and neonatal risk factors. The model, with demonstrated accuracy and reliability, holds significant potential for improving neonatal outcomes through timely interventions. Future research should aim at external validation and inclusion of broader clinical data to enhance the model's applicability and generalizability.
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Affiliation(s)
- Nhu Thi Huynh Tran
- Department of Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Ly Cong Tran
- Department of Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Duc Long Tran
- Department of Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Vinh The Nguyen
- Department of Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - My Hoang Le
- Department of Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
| | - Nhi Thi Kieu Nguyen
- Department of Pediatrics, Can Tho University of Medicine and Pharmacy, Can Tho, VNM
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47
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Hasibuan BS, Dasatjipta G, Lubis BM, Sanny S. Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in diagnosing neonatal sepsis. NARRA J 2024; 4:e763. [PMID: 39280270 PMCID: PMC11391992 DOI: 10.52225/narra.v4i2.763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 05/27/2024] [Indexed: 09/18/2024]
Abstract
Clinical manifestations of neonatal sepsis are often unspecified. Therefore, sepsis biomarkers could be used to support diagnosis while waiting for blood culture results, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The aim of this study was to evaluate the role of NLR and PLR as diagnostic markers in neonatal sepsis. A cross-sectional study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, from April to October 2019. This study included neonates aged less than 28 days, diagnosed with suspected sepsis, and had no previous history of antibiotics administration. Patients underwent clinical assessment, laboratory examination, and blood culture. Patients were grouped into sepsis and non-sepsis based on the blood culture results. The median hematological examination and the range of NLR and PLR in both the sepsis and non-sepsis groups were subjected to analysis using the Mann-Whitney U test to assess differences. NLR and PLR optimal cut-off values were determined using a receiver operator curve (ROC) with a confidence interval of 95%. A total of 137 neonates were enrolled, of which 49 were classified as sepsis and 89 as non-sepsis based on blood culture results. The optimal cutoff values for NLR and PLR were 2.75 and 11.73. Using those cutoff values, NLR and PLR could predict neonatal sepsis with sensitivities of 52.1% and 47.9%, specificities of 50.6% and 47.2%, area under the curve (AUC) of 0.46 and 0.47, with p=0.525 and p=0.662, respectively. Further investigation is warranted to refine the NLR and PLR utility and enhance diagnostic accuracy in clinical practices.
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Affiliation(s)
- Beby S Hasibuan
- Department of Pediatrics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - Guslihan Dasatjipta
- Department of Pediatrics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - Bugis M Lubis
- Department of Pediatrics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - Sanny Sanny
- Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
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Singu BS, Pieper CH, Verbeeck RK, Ette EI. Predictors of gentamicin therapy failure in neonates with sepsis. Pharmacol Res Perspect 2024; 12:e1250. [PMID: 39105353 DOI: 10.1002/prp2.1250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 06/15/2024] [Accepted: 07/04/2024] [Indexed: 08/07/2024] Open
Abstract
Sepsis is a common disease with high morbidity and mortality among newborns in intensive care units world-wide. Gram-negative bacillary bacteria are the major source of infection in neonates. Gentamicin is the most widely used aminoglycoside antibiotic in empiric therapy against early-onset sepsis. However, therapy failure may result due to various factors. The purpose of this study was to identify predictors of gentamicin therapy failure in neonates with sepsis. This was a prospective cross-sectional study at the Neonatal Intensive Care Unit at Windhoek Central Hospital over a period of 5 months in 2019. Neonates received intravenous gentamicin 5 mg/kg/24 h in combination with either benzylpenicillin 100 000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Logistic regression modeling was performed to determine the predictors of treatment outcomes. 36% of the 50 neonates were classified as having gentamicin treatment failure. Increasing treatment duration by 1 day resulted in odds of treatment failure increasing from 1.0 to 2.41. Similarly, one unit increase in CRP increases odds of gentamicin treatment failure by 49%. The 1 kg increase in birthweight reduces the log odds of treatment failure by 6.848, resulting in 99.9% decrease in the odds of treatment failure. One unit increase in WBC reduces odds of gentamicin treatment failure by 27%. Estimates of significant predictors of treatment failure were precise, yielding odds ratios that were within 95% confidence interval. This study identified the following as predictors of gentamicin therapy failure in neonates: prolonged duration of treatment, elevated C-reactive protein, low birthweight, and low white blood cell count.
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Affiliation(s)
| | | | - Roger Karel Verbeeck
- School of Pharmacy, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia
| | - Ene I Ette
- School of Pharmacy, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia
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49
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Boskabadi H, Najafi A, Saghafi N, Sayedi SJ, Moradi A, Zakerihamidi M. Neonatal complications of premature rupture of membranes in mothers receiving cefotaxime and ampicillin: A randomized clinical trial. J Infect Prev 2024:17571774241261911. [PMID: 39555001 PMCID: PMC11562933 DOI: 10.1177/17571774241261911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 04/12/2024] [Indexed: 11/19/2024] Open
Abstract
Introduction Premature rupture of membranes (PROM) is one of the most common and important causes of premature births and peripartum mortality. Maternal antibiotic treatment affects the infantile prognosis. This study was conducted to compare the efficacy of Ampicillin and Cefotaxime administered for the parturients on neonatal outcomes. Material and Methods A comparison between the effects of Cefotaxime and Ampicillin on infantile complications of PROM was done in this clinical trial. Two hundred and twenty parturients with PROM who needed antibiotic therapy were randomized in two groups of control (Ampicillin) and intervention (Cefotaxime) treatments. The maternal/fetal statuses up to accouchement and the infants' status up to transfer to neonatal intensive care unit, death, or discharge from hospital were followed. The Apgar score, cardiac, respiratory and nervous systems, infection, immaturity, asphyxia, and mortality rates were compared in both groups. Results The differences between the two groups were significant in: Apgar score min1 and min5, need for resuscitation, asphyxia, need for hospitalization, infection, and mortality rate. Conclusion Administration of Cefotaxime in parturients with PROM improved the Apgar scores and decreased respiratory complications, infection, asphyxia, mortality rate, and need for ICU hospitalization in infants.
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Affiliation(s)
- Hassan Boskabadi
- Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Najafi
- Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nafiseh Saghafi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sayed J Sayedi
- Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Moradi
- Orthopedic Research Centre, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Zakerihamidi
- Department of Midwifery, School of Medical Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
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50
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Strunk T, Molloy EJ, Mishra A, Bhutta ZA. Neonatal bacterial sepsis. Lancet 2024; 404:277-293. [PMID: 38944044 DOI: 10.1016/s0140-6736(24)00495-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 02/06/2024] [Accepted: 03/07/2024] [Indexed: 07/01/2024]
Abstract
Neonatal sepsis remains one of the key challenges of neonatal medicine, and together with preterm birth, causes almost 50% of all deaths globally for children younger than 5 years. Compared with advances achieved for other serious neonatal and early childhood conditions globally, progress in reducing neonatal sepsis has been much slower, especially in low-resource settings that have the highest burden of neonatal sepsis morbidity and mortality. By contrast to sepsis in older patients, there is no universally accepted neonatal sepsis definition. This poses substantial challenges in clinical practice, research, and health-care management, and has direct practical implications, such as diagnostic inconsistency, heterogeneous data collection and surveillance, and inappropriate treatment, health-resource allocation, and education. As the clinical manifestation of neonatal sepsis is frequently non-specific and the current diagnostic standard blood culture has performance limitations, new improved diagnostic techniques are required to guide appropriate and warranted antimicrobial treatment. Although antimicrobial therapy and supportive care continue as principal components of neonatal sepsis therapy, refining basic neonatal care to prevent sepsis through education and quality improvement initiatives remains paramount.
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Affiliation(s)
- Tobias Strunk
- Neonatal Directorate, King Edward Memorial Hospital, Child and Adolescent Health Service, Perth, WA, Australia; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
| | - Eleanor J Molloy
- Discipline of Paediatrics, Trinity College, University of Dublin and Trinity Research in Childhood Centre, Dublin, Ireland; Children's Health Hospital at Tallaght, Tallaght University Hospital, Dublin, Ireland; Trinity Translational Medicine Institute, St James Hospital, Dublin, Ireland; Neonatology, Children's Health Hospital at Crumlin, Dublin, Ireland; Paediatrics, Coombe Women's and Infant's University Hospital, Dublin, Ireland
| | - Archita Mishra
- Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
| | - Zulfiqar A Bhutta
- Centre for Global Child Health, Hospital for Sick Children, Toronto, ON, Canada; Institute for Global Health and Development, The Aga Khan University South-Central Asia, Karachi, Pakistan
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