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Sivakumar N, Srinivasan L, Grundmeier RW, Harris MC. Demystifying Prolonged Antibiotic Use for Blood Culture-negative Sepsis Evaluations in the Neonatal Intensive Care Unit. Pediatr Infect Dis J 2025:00006454-990000000-01307. [PMID: 40294328 DOI: 10.1097/inf.0000000000004836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
OBJECTIVE This study aimed to determine the incidence and clinical characteristics of infants evaluated and treated with a prolonged course of antibiotics for culture-negative sepsis in a quaternary Neonatal Intensive Care Unit (NICU) over a 4-year period. STUDY DESIGN Retrospective chart review of patients in the NICU at Children's Hospital of Philadelphia who had negative blood cultures and received ≥5 days of antibiotics. Data collection included demographics, clinical and laboratory data, and underlying diagnoses. Statistical analysis included Mann-Whitney and chi-square tests, and multivariable logistic regression. RESULTS We identified 774 culture-negative sepsis evaluations where antibiotic treatment was continued ≥5 days. While the majority were attributed to a focal etiology, 146 had negative blood cultures and no focal source. Infants with no focal source were younger at the time of sepsis evaluation, of greater gestational age, and more frequently required extracorporeal membrane oxygenation (P < 0.001). In multivariable analysis, evaluations for early-onset disease and need for extracorporeal membrane oxygenation were increased among infants with no focal source (P < 0.01). Although rates of invasive ventilation, and central venous catheters were similar, length of stay and mortality were significantly higher in late-onset episodes (P < 0.001 and P = 0.029, respectively). Consultation with the infectious disease team increased during the study period (P = 0.002). CONCLUSIONS Although it is challenging to limit the initiation of antibiotics in infants with complex underlying disease processes with concern for sepsis, minimizing antibiotic use can be achieved by timely discontinuation when cultures are negative. A robust antimicrobial stewardship program can identify valid reasons for prolonged antibiotic administration and suggest approaches to minimize antibiotic exposure.
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Affiliation(s)
- Nithya Sivakumar
- From the Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Lakshmi Srinivasan
- From the Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Robert W Grundmeier
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
- Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Mary Catherine Harris
- From the Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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Arnesen AB, Møller N, Vibede LD, Vestergaard K, Holm SK, Trier C, Stanchev H, Dayani G, Nygaard U, Carlsen EM, Hansen BM. Use of Antibiotics and Severe Bacterial Infections Within the First 6 Months of Life-A Population-Based Cohort Study From East Denmark. Acta Paediatr 2025. [PMID: 40255168 DOI: 10.1111/apa.70103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 04/09/2025] [Accepted: 04/11/2025] [Indexed: 04/22/2025]
Abstract
AIM To investigate antibiotic exposure and the incidence of severe bacterial infections during the first 6 months of life in preterm infants born between 28 and 37 weeks of gestation. METHODS Retrospective population-based study of preterm infants in East Denmark, 2019-2021. Participants were identified based on dispensed antibiotics through the joint electronic health system. Infectious episodes were defined as suspected (≤ 4 days of treatment), probable (≥ 5 days of treatment) or proven if blood culture positive. RESULTS During the first 6 months of life, 557 of 5128 (11%) preterm infants received 635 courses. Two-thirds of all antibiotic courses were administered within the first 72 h of life, with 12 proven infections, that is, 2.3 per 1000 live births. Beyond 72 h of age, nearly all bacterial infection episodes were hospital acquired, with 24 proven infections, that is, 4.7 per 1000 live births. Three infants had sepsis-related mortality, that is, 0.58 per 1000 live births. CONCLUSION In preterm Danish infants aged 28-37 weeks of gestation, antibiotic treatment for suspected or probable infections was 15 times higher than for confirmed infections. Antibiotic exposure was high in this group of preterm infants, while confirmed infections were low.
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Affiliation(s)
- Anna Bjerager Arnesen
- Department of Neonatology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
- Department of Paediatrics and Adolescent Medicine, Nordsjællands Hospital, Hillerød, Copenhagen University, Copenhagen, Denmark
| | - Nini Møller
- Department of Gynaecology and Obstetrics, Nordsjællands Hospital, Hillerød, Copenhagen University, Copenhagen, Denmark
| | - Louise Dyrberg Vibede
- Department of Paediatrics and Adolescent Medicine, Herlev Hospital, Copenhagen University, Herlev, Denmark
| | - Kristian Vestergaard
- Department of Paediatrics and Adolescent Medicine, Holbæk Hospital, Copenhagen University, Holbæk, Denmark
| | - Sara Krøis Holm
- Department of Neonatology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
- Department of Paediatrics and Adolescent Medicine, Hvidovre Hospital Copenhagen University, Hvidovre, Denmark
| | - Cæcilie Trier
- Department of Paediatrics and Adolescent Medicine, Nykøbing-Falster Hospital, Copenhagen University, Nykøbing-Falster, Denmark
| | - Hristo Stanchev
- Department of Paediatrics and Adolescent Medicine, Slagelse Hospital, Copenhagen University, Slagelse, Denmark
| | - Gholamreza Dayani
- Department of Paediatrics and Adolescent Medicine, Roskilde Hospital, Copenhagen University, Roskilde, Denmark
| | - Ulrikka Nygaard
- Department of Paediatrics, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Emma Malchau Carlsen
- Department of Neonatology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Bo Mølholm Hansen
- Department of Paediatrics and Adolescent Medicine, Nordsjællands Hospital, Hillerød, Copenhagen University, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Jennings MR, Elhaissouni N, Colantuoni E, Prochaska EC, Johnson J, Xiao S, Clark RH, Greenberg RG, Benjamin DK, Milstone AM. Epidemiology and Mortality of Invasive Staphylococcus aureus Infections in Hospitalized Infants. JAMA Pediatr 2025:2832660. [PMID: 40227743 PMCID: PMC11997858 DOI: 10.1001/jamapediatrics.2025.0429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 01/08/2025] [Indexed: 04/15/2025]
Abstract
Importance Historically, Staphylococcus aureus has been a leading cause of morbidity and mortality in the neonatal intensive care unit (NICU). The current incidence and attributable mortality of late-onset invasive S aureus infection in hospitalized infants is unknown. Objective To estimate the incidence and attributable mortality of late-onset S aureus infection among hospitalized infants in the US. Design, Setting, and Participants This retrospective cohort study included an emulated trial among a national convenience sample of 315 NICUs within the US between 2016 and 2021. Participants were infants aged at least 4 postnatal days who were hospitalized in a participating NICU. Data were analyzed from May to August 2024. Exposures The primary exposures were birth weight and postnatal age. Main Outcomes and Measures The outcomes were the incidence and attributable mortality of late-onset invasive S aureus infection. Methicillin-resistant and methicillin-sensitive S aureus classification was not universally available; thus, all invasive S aureus infections were pooled. Results From 468 201 infants (260 491 [55.6%] male; median [IQR] gestational age, 36 [33-38] weeks) eligible for analysis, 1724 infants experienced 1762 infections for an overall incidence of 37.6 (95% CI, 35.9-39.4) invasive S aureus infections per 10 000 infants. Most infants with invasive infections were 32 weeks' gestational age or younger (1394 infants [80.9%]), very low birth weight (VLBW; ie, <1500 g) (1318 infants [76.5%]), and/or had a central line during their hospital stay (1509 infants [87.5%]). Invasive infections mostly included bloodstream infections (1505 infections [85.4%]), and 1160 infections (65.8%) occurred within 4 to 28 postnatal days. Birth weight inversely correlated with incidence: infants with VLBW experienced a more than 20-fold higher incidence relative to infants born weighing at least 1500 g (227.1 [95% CI, 215.3-239.4] vs 10.1 [95% CI, 9.1-11.1] infections per 10 000 infants). Most deaths following invasive infection occurred among VLBW infants (189 of 209 deaths [90.4%]). Compared with matched infants without a late-onset invasive S aureus infection, infected infants had an absolute difference in mortality rate of 5.3% (95% CI, 3.8%-6.8%). Conclusions and Relevance This cohort study found late-onset invasive S aureus infection and subsequent attributable mortality disproportionally affected infants with VLBW. Targeted infection prevention and control measures are necessary to reduce morbidity and mortality from invasive S aureus infections in this vulnerable population.
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Affiliation(s)
- Maria Rain Jennings
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nora Elhaissouni
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Elizabeth Colantuoni
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Erica C. Prochaska
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Hospital Epidemiology and Infection Control, Johns Hopkins Hospital, Baltimore, Maryland
| | - Julia Johnson
- Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Maryland
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Shaoming Xiao
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Rachel G. Greenberg
- Department of Pediatrics Duke University School of Medicine, Durham, North Carolina
- Duke Clinical Research Institute, Durham, North Carolina
| | - Daniel K. Benjamin
- Department of Pediatrics Duke University School of Medicine, Durham, North Carolina
- Duke Clinical Research Institute, Durham, North Carolina
| | - Aaron M. Milstone
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Hospital Epidemiology and Infection Control, Johns Hopkins Hospital, Baltimore, Maryland
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Balks J, Grumaz S, Mazzitelli S, Neder U, Lemloh L, Melaku T, Glaser K, Mueller A, Kipfmueller F. Microbial cell-free DNA-sequencing as an addition to conventional diagnostics in neonatal sepsis. Pediatr Res 2025; 97:614-624. [PMID: 39143203 PMCID: PMC12015174 DOI: 10.1038/s41390-024-03448-1] [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: 03/15/2024] [Revised: 06/04/2024] [Accepted: 07/24/2024] [Indexed: 08/16/2024]
Abstract
BACKGROUND Bloodstream infections remain a challenge for neonatologists, as traditional culture-based methods are time-consuming and rely on adequate blood volume. Next-generation sequencing (NGS) offers an alternative, as it can identify microbial cell-free DNA (mcfDNA) in a small blood sample, providing rapid pathogen detection. This study aimed to assess the diagnostic performance of DISQVER®-NGS compared to blood cultures in neonatal patients with suspected sepsis. METHODS In neonates with suspected sepsis, blood cultures and samples for NGS were prospectively collected. Patients were divided into four categories: 1) sepsis, blood culture positive, 2) clinical sepsis, culture negative, 3) suspected sepsis, 4) validation cohort. RESULTS NGS detected bacterial, viral or fungal mcfDNA in 24 of 82 samples. Blood cultures were collected in 46 of 84 patients (15/46 positive). DISQVER® correctly identified pathogens in 9/15 patients with a positive blood culture, two with intrinsic resistance to their antibiotic regimen. In seven samples NGS reported the mcfDNA of bacteria that could have theoretically grown in culture but did not. CONCLUSIONS NGS may enhance sensitivity in sepsis diagnostics by detecting mcfDNA in neonates with suspected sepsis. Interpreting NGS results requires correlation with clinical data, laboratory values, and routine microbiological tests for a comprehensive understanding of the patient's condition. IMPACT Conventional blood culture methods have limitations in accuracy and turnaround time. The study aimed to investigate the diagnostic performance of the Next-Generation Sequencing method DISQVER® compared to traditional blood cultures in neonatal patients with suspected sepsis. Our findings suggest that NGS has the potential to augment the precision of conventional diagnostic techniques, can lead to improved detection of pathogens and targeted treatment approaches in neonatal sepsis. It is emphasized that further validation and integration with clinical and microbiological data are required to ensure optimal clinical utility.
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Affiliation(s)
- Julian Balks
- Division of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
| | | | | | | | - Lotte Lemloh
- Division of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany
| | - Tamene Melaku
- Division of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany
| | - Kirsten Glaser
- Division of Neonatology, Department of Women's and Children's Health, University Medical Center Leipzig, Leipzig, Germany
| | - Andreas Mueller
- Division of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany
| | - Florian Kipfmueller
- Division of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany.
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Lawrence SM, Wynn JL, Gordon SM. Neonatal bacteremia and sepsis. REMINGTON AND KLEIN'S INFECTIOUS DISEASES OF THE FETUS AND NEWBORN INFANT 2025:183-232.e25. [DOI: 10.1016/b978-0-323-79525-8.00015-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Buttera M, Mazzotti S, Zini T, Corso L, Dallai V, Miselli F, Bedetti L, Rossi K, Spaggiari E, Iughetti L, Lugli L, Berardi A. Bacterial Meningitis in Infants Under 90 Days of Age: A Retrospective Single-Center Study. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1411. [PMID: 39767840 PMCID: PMC11675066 DOI: 10.3390/children11121411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/04/2024] [Accepted: 11/13/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Bacterial meningitis (BM) in infants is a serious condition that can lead to significant complications. Lumbar puncture (LP) is essential to provide diagnoses, however false negatives may result if LP is performed after the starting of antibiotic therapy. METHODS We conducted a retrospective analysis of infants of any gestational age with BM within their first 90 days of life and admitted to the Neonatal Intensive Care Unit of Modena Policlinico between 1 January 2011, and 31 December 2023. RESULTS A total of 44 episodes of meningitis were confirmed in 40 infants, diagnosed by positive cerebrospinal fluid cultures (n = 37), polymerase chain reaction testing (n = 4), or both methods (n = 3). Three out of forty infants (8%) experienced a relapse of meningitis. Most episodes (31/44, 70%) occurred in preterm infants. The incidence of early-onset meningitis was lower than that of late-onset (0.18 vs. 0.94 cases per 1000 births, respectively), with Gram-positive accounting for most cases (27/44, 61%). LP was performed prior to antibiotic administration in most episodes (30/44, 68%). Two preterm infants (5%) died from meningitis-related complications. Forty-two episodes occurred among thirty-eight surviving infants; brain lesions were detected through brain ultrasound or MRI in nine out of forty-two episodes (21%). CONCLUSIONS Preterm infants have higher rates of BM, brain lesions or case fatalities. Early diagnosis and prompt antibiotic treatment are critical to improve outcomes.
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Affiliation(s)
- Martina Buttera
- School of Pediatrics Residency, University of Modena and Reggio Emilia, 41224 Modena, Italy; (M.B.); (L.C.)
| | - Sofia Mazzotti
- School of Pediatrics Residency, University of Modena and Reggio Emilia, 41224 Modena, Italy; (M.B.); (L.C.)
| | - Tommaso Zini
- Pediatric Unit, Arcispedale Santa Maria Nuova, University of Modena and Reggio Emilia, 41224 Modena, Italy
| | - Lucia Corso
- School of Pediatrics Residency, University of Modena and Reggio Emilia, 41224 Modena, Italy; (M.B.); (L.C.)
| | - Valeria Dallai
- Degree Program in Medicine and Surgery, University of Modena and Reggio Emilia, 41224 Modena, Italy
| | - Francesca Miselli
- Neonatal Intensive Care Unit, University Hospital of Modena, 41224 Modena, Italy; (F.M.); (A.B.)
| | - Luca Bedetti
- Neonatal Intensive Care Unit, University Hospital of Modena, 41224 Modena, Italy; (F.M.); (A.B.)
| | - Katia Rossi
- Neonatal Intensive Care Unit, University Hospital of Modena, 41224 Modena, Italy; (F.M.); (A.B.)
| | - Eugenio Spaggiari
- Neonatal Intensive Care Unit, University Hospital of Modena, 41224 Modena, Italy; (F.M.); (A.B.)
| | - Lorenzo Iughetti
- School of Pediatrics Residency, University of Modena and Reggio Emilia, 41224 Modena, Italy; (M.B.); (L.C.)
- Pediatric Unit, University Hospital of Modena, 41124 Modena, Italy
| | - Licia Lugli
- Neonatal Intensive Care Unit, University Hospital of Modena, 41224 Modena, Italy; (F.M.); (A.B.)
| | - Alberto Berardi
- Neonatal Intensive Care Unit, University Hospital of Modena, 41224 Modena, Italy; (F.M.); (A.B.)
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Crepin DM, Chavignon M, Verhoeven PO, Laurent F, Josse J, Butin M. Staphylococcus capitis: insights into epidemiology, virulence, and antimicrobial resistance of a clinically relevant bacterial species. Clin Microbiol Rev 2024; 37:e0011823. [PMID: 38899876 PMCID: PMC11391707 DOI: 10.1128/cmr.00118-23] [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: 06/21/2024] Open
Abstract
SUMMARYStaphylococcus capitis is divided into two subspecies, S. capitis subsp. ureolyticus (renamed urealyticus in 1992; ATCC 49326) and S. capitis subsp. capitis (ATCC 27840), and fits with the archetype of clinically relevant coagulase-negative staphylococci (CoNS). S. capitis is a commensal bacterium of the skin in humans, which must be considered an opportunistic pathogen of interest particularly as soon as it is identified in a clinically relevant specimen from an immunocompromised patient. Several studies have highlighted the potential determinants underlying S. capitis pathogenicity, resistance profiles, and virulence factors. In addition, mobile genetic element acquisitions and mutations contribute to S. capitis genome adaptation to its environment. Over the past decades, antibiotic resistance has been identified for S. capitis in almost all the families of the currently available antibiotics and is related to the emergence of multidrug-resistant clones of high clinical significance. The present review summarizes the current knowledge concerning the taxonomic position of S. capitis among staphylococci, the involvement of this species in human colonization and diseases, the virulence factors supporting its pathogenicity, and the phenotypic and genomic antimicrobial resistance profiles of this species.
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Affiliation(s)
- Deborah M Crepin
- CIRI, Centre International de Recherche en Infectiologie, Staphylococcal pathogenesis team, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR 5308, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Marie Chavignon
- CIRI, Centre International de Recherche en Infectiologie, Staphylococcal pathogenesis team, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR 5308, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Paul O Verhoeven
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR 5308, Ecole Normale Supérieure de Lyon, Lyon, France
- Faculté de Médecine, Université Jean Monnet, St-Etienne, France
- Service des agents infectieux et d'hygiène, Centre Hospitalier Universitaire de St-Etienne, St-Etienne, France
| | - Frédéric Laurent
- CIRI, Centre International de Recherche en Infectiologie, Staphylococcal pathogenesis team, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR 5308, Ecole Normale Supérieure de Lyon, Lyon, France
- Institut des Agents Infectieux, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
- Centre National de Référence des Staphylocoques, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Jérôme Josse
- CIRI, Centre International de Recherche en Infectiologie, Staphylococcal pathogenesis team, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR 5308, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Marine Butin
- CIRI, Centre International de Recherche en Infectiologie, Staphylococcal pathogenesis team, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR 5308, Ecole Normale Supérieure de Lyon, Lyon, France
- Service de Néonatologie et Réanimation Néonatale, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
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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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Gulden S, Cervellini G, Colombo M, Marangoni MB, Taccani V, Pesenti N, Raffaeli G, Araimo G, Osnaghi S, Fumagalli M, Garrido F, Villamor E, Cavallaro G. Hyperbilirubinemia and retinopathy of prematurity: a retrospective cohort study. Eur J Pediatr 2024; 183:3809-3818. [PMID: 38877325 DOI: 10.1007/s00431-024-05630-3] [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: 04/09/2024] [Revised: 05/22/2024] [Accepted: 05/24/2024] [Indexed: 06/16/2024]
Abstract
Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g. Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP. Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP.
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Affiliation(s)
- Silvia Gulden
- Neonatal Intensive Care Unit, Sant'Anna Hospital, 22042, Como, Italy
| | - Gaia Cervellini
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Marta Colombo
- Neonatal Intensive Care Unit, Sant'Anna Hospital, 22042, Como, Italy
| | - Maria Beatrice Marangoni
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Vittoria Taccani
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Nicola Pesenti
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Revelo Datalabs S.R.L, 20142, Milan, Italy
| | - Genny Raffaeli
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy.
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy.
| | - Gabriella Araimo
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - Silvia Osnaghi
- Department of Ophthalmology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - Monica Fumagalli
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Felipe Garrido
- Neonatal Intensive Care Unit, Clínica Universidad de Navarra, 28027, Madrid, Spain
| | - Eduardo Villamor
- Division of Neonatology, MosaKids Children's Hospital, Maastricht University Medical Center (MUMC+), Research Institute for Oncology and Reproduction (GROW), Maastricht University, 6202AZ, Maastricht, The Netherlands
| | - Giacomo Cavallaro
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
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10
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Prochaska EC, Xiao S, Colantuoni E, Clark RH, Johnson J, Mukhopadhyay S, Kalu IC, Zerr DM, Reich PJ, Roberts J, Flannery DD, Milstone AM. Hospital-Onset Bacteremia Among Neonatal Intensive Care Unit Patients. JAMA Pediatr 2024; 178:792-799. [PMID: 38913368 PMCID: PMC11197452 DOI: 10.1001/jamapediatrics.2024.1840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 04/03/2024] [Indexed: 06/25/2024]
Abstract
Importance The Centers for Disease Control and Prevention plans to introduce hospital-onset bacteremia (HOB) as a health care-associated infection measure. The epidemiology and clinical characteristics of HOB among infants admitted to the neonatal intensive care unit (NICU) are unknown. Objective To estimate the rate of HOB among infants admitted to the NICU, measure the association of HOB risk with birth weight group and postnatal age, and estimate HOB-attributable mortality. Design, Setting, and Participants This retrospective multicenter cohort study and emulated trial from 2016 to 2021 included a convenience sample of 322 NICUs in the United States. Participants were infants admitted to participating NICUs for 4 or more days. Exposures The primary exposures were birth weight and postnatal age. Additional exposures included small for gestational age and central line presence. Main Outcomes and Measures The primary study outcomes were HOB and HOB-attributable mortality. Results Of 451 443 included infants, 250 763 (55.6%) were male, 200 680 (44.4%) were female, and 62 091 (13.8%) were born 1500 g or less. Of 9015 HOB events that occurred among 8356 infants (2%) during 8 163 432 days at risk (unadjusted incidence rate, 1.1 per 1000 patient-days; 95% CI, 1.0-1.2), 4888 HOB events (54.2%) occurred in the absence of a central line. Within the first 2 weeks after birth, the HOB rate was 14.2 per 1000 patient-days (95% CI, 12.6-16.1) among infants born 750 g or less, to 0.4 events per 1000 patient-days among infants born more than 2500 g (95% CI, 0.4-0.5). Among infants born 750 g or less, the relative HOB risk decreased by 90% after day 42 compared with days 4 to 14 (incidence rate ratio [IRR], 0.10; 95% CI, 0.1-0.1). Conversely, among infants born more than 2500 g, the relative HOB risk increased by 50% after day 42 compared with days 4 to 14 (IRR, 1.5, 95% CI, 1.2-1.9). Compared with otherwise similar infants without HOB, infants with HOB had an absolute difference in attributable mortality of 5.5% (95% CI, 4.7-6.3). Conclusions and Relevance This study found that HOB events in the NICU are associated with increased mortality. Birth weight is an important risk factor for HOB; however, the relative rate of HOB decreases over postnatal age among low-birth-weight infants and increases among infants born more than 2500 g. Identifying strategies to prevent HOB and programs to decrease HOB risk are urgently needed to reduce infant mortality.
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Affiliation(s)
- Erica C. Prochaska
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Hospital Epidemiology and Infection Control, Johns Hopkins Health System, Baltimore, Maryland
| | - Shaoming Xiao
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Elizabeth Colantuoni
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | | | - Julia Johnson
- Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Sagori Mukhopadhyay
- Division of Neonatology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Ibukunoluwa C. Kalu
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
| | - Danielle M. Zerr
- Division of Infectious Diseases, Department of Pediatrics, University of Washington and Seattle Children’s Hospital, Seattle
| | - Patrick J. Reich
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
| | - Jessica Roberts
- Division of Neonatology, Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, Georgia
| | - Dustin D. Flannery
- Division of Neonatology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Aaron M. Milstone
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Hospital Epidemiology and Infection Control, Johns Hopkins Health System, Baltimore, Maryland
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11
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Regassa DA, Nagaash RS, Habtu BF, Haile WB. Diagnostic significance of complete blood cell count and hemogram-derived markers for neonatal sepsis at Southwest Public Hospitals, Ethiopia. World J Clin Pediatr 2024; 13:92392. [PMID: 38947992 PMCID: PMC11212765 DOI: 10.5409/wjcp.v13.i2.92392] [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: 01/24/2024] [Revised: 02/11/2024] [Accepted: 04/12/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Neonatal sepsis is defined as an infection-related condition characterized by signs and symptoms of bacteremia within the first month of life. It is the leading cause of mortality and morbidity among newborns. While several studies have been conducted in other parts of world to assess the usefulness of complete blood count parameters and hemogram-derived markers as early screening tools for neonatal sepsis, the associations between sepsis and its complications with these blood parameters are still being investigated in our setting and are not yet part of routine practice. AIM To evaluate the diagnostic significance of complete blood cell count hemogram-derived novel markers for neonatal sepsis among neonates attending public hospitals in the southwest region of Oromia, Ethiopia, through a case control study. METHODS A case control study was conducted from October 2021 to October 2023 Sociodemographic, clinical history, and laboratory test results data were collected using structured questionnaires. The collected data were entered into Epi-data 3.1 version and exported to SPSS-25 for analysis. Chi-square, independent sample t-test, and receiver operator characteristics curve of curve were used for analysis. A P-value of less than 0.05 was considered statistically significant. RESULTS In this study, significant increases were observed in the following values in the case group compared to the control group: In white blood cell (WBC) count, neutrophils, monocyte, mean platelet volume (MPV), neutrophils to lymphocyte ratio, monocyte to lymphocyte ratio (MLR), red blood cell width to platelet count ratio (RPR), red blood width coefficient variation, MPV to RPR, and platelet to lymphocyte ratio. Regarding MLR, a cut-off value of ≥ 0.26 was found, with a sensitivity of 68%, a specificity of 95%, a positive predictive value (PPV) of 93.2%, and a negative predictive value (NPV) of 74.8%. The area under the curve (AUC) was 0.828 (P < 0.001). For WBC, a cut-off value of ≥ 11.42 was identified, with a sensitivity of 55%, a specificity of 89%, a PPV of 83.3%, and a NPV of 66.4%. The AUC was 0.81 (P < 0.001). Neutrophils had a sensitivity of 67%, a specificity of 81%, a PPV of 77.9%, and a NPV of 71.1%. The AUC was 0.801, with a cut-off value of ≥ 6.76 (P = 0.001). These results indicate that they were excellent predictors of neonatal sepsis diagnosis. CONCLUSION The findings of our study suggest that certain hematological parameters and hemogram-derived markers may have a potential role in the diagnosis of neonatal sepsis.
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Affiliation(s)
- Dereje Abebe Regassa
- Department of Medical Laboratory Sciences, Wolkite University, Wolkite 11330, Ethiopia
| | - Rahel Shumi Nagaash
- Department of Medical Laboratory Sciences, Wolkite University, Wolkite 11330, Ethiopia
| | - Bisirat Fikadu Habtu
- Department of Medical Laboratory Sciences, Wolkite University, Wolkite 11330, Ethiopia
| | - Woyesa Beyene Haile
- Department of Medical Laboratory Sciences, Dire Dawa University, Dire Dawa 3000, Ethiopia
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12
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Oncel MY, Cizmeci MN, Karadag-Oncel E, Elvan-Tuz A, Canpolat FE, Akin MA, Uslu S, Cetinkaya M, Erdeve O, Koc E. Epidemiology and Outcomes of Neonatal Meningitis: Results of the Turkish Neo-Meningitis Nationwide Study. Pediatr Infect Dis J 2024; 43:365-370. [PMID: 38134373 DOI: 10.1097/inf.0000000000004197] [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] [Indexed: 12/24/2023]
Abstract
OBJECTIVE To investigate the incidence and etiology of neonatal meningitis and to assess the associated risk factors, complications and outcomes in a nationwide multicenter retrospective descriptive study. METHOD Twenty-seven centers from 7 geographical regions participated in the study. Newborns with a positive cerebrospinal fluid culture and/or cerebrospinal fluid polymerase chain reaction were included in the study. Demographic characteristics, clinical, laboratory and neuroimaging findings and mortality characteristics were analyzed. RESULTS A total of 634 confirmed cases of neonatal meningitis were included in the final analysis. The incidence was 2.51 per 1000 intensive care unit hospitalizations and mortality was observed in 149 (23.5%). Gram-positive bacteria were the predominant pathogens (54.5%), with coagulase-negative Staphylococci accounting for 45.3% of the cases, followed by Gram-negative organisms (37.3%). Viral and fungal organisms were isolated in 3.2% and 1.7% of the infants, respectively. Gram-negative culture growth was more common in infants who died (51% vs. 34.6%; P < 0.001). In the multivariable model, the odds of mortality was higher in those with respiratory distress requiring invasive ventilatory support [odds ratio (OR): 10.3; 95% confidence interval (CI): 4.9-21.7; P < 0.01], hypotension requiring inotropes (OR: 4.4; 95% CI: 2.7-7.1; P < 0.001), low birth weight status (OR: 2.5; 95% CI: 1.4-4.6; P = 0.002), lack of exposure to antenatal steroids (OR: 2.4; 95% CI: 1.3-4.4; P = 0.005) and the presence of concomitant sepsis (OR: 1.9; 95% CI: 1.1-3.2; P = 0.017). CONCLUSIONS In this nationwide study, neonatal meningitis was found to be associated with high mortality. Coagulase-negative Staphylococci was the most common causative microorganism followed by Gram-negative bacteria. Severe clinical presentation with invasive mechanical ventilation and inotrope requirement, as well as concomitant sepsis, low birth weight status and lack of exposure to antenatal steroids, were found to be independent risk factors for mortality.
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Affiliation(s)
- Mehmet Yekta Oncel
- From the Division of Neonatology, Department of Pediatrics, Izmir Katip Celebi University, Izmir, Türkiye
| | - Mehmet N Cizmeci
- Division of Neonatology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Eda Karadag-Oncel
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Dokuz Eylul University, Izmir, Türkiye
| | - Aysegul Elvan-Tuz
- Division of Pediatric Infectious Diseases , Izmir Tepecik Training and Research Hospital, University of Health Sciences, Izmir, Türkiye
| | - Fuat Emre Canpolat
- Neonatal Clinic, Ministry of Health Ankara City Hospital, Ankara, Türkiye
| | - Mustafa Ali Akin
- Department of Pediatrics, Ondokuz Mayis University, Samsun, Türkiye
| | - Sinan Uslu
- Neonatal Clinic, Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences
| | - Merih Cetinkaya
- Neonatal Clinic, Ministry of Health Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye
| | | | - Esin Koc
- Department of Pediatrics, Gazi University, Ankara, Türkiye
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13
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Wang X, Huang Z, Ma Y. Development and Validation of a Multivariable Predictive Model for the Risk of Histologic Chorioamnionitis in Patients with Premature Rupture of Membranes in the Late Preterm and Term. Int J Gen Med 2024; 17:141-152. [PMID: 38249617 PMCID: PMC10799642 DOI: 10.2147/ijgm.s445374] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 01/10/2024] [Indexed: 01/23/2024] Open
Abstract
Background This study aimed to develop and validate a model to predict histologic chorioamnionitis (HCA) risk in late preterm and term premature rupture of membranes (PROM) patients using clinical and laboratory parameters. Methods We conducted a retrospective study on 116 late preterm and term PROM cases, divided into a training (n=81) and a validation set (n=35). A multivariable logistic regression model was developed using the training set. Performance was assessed via the area under the receiver operating characteristic curve (AUC) and net reclassification index (NRI). Decision curve analysis (DCA) evaluated the model's clinical utility. Additionally, nomograms and a web version of the model were developed. Results In the training set, the combined model constructed using maternal BMI, gravidity, amniotic fluid characteristics, and prenatal white blood cell (WBC) count showed significantly higher AUC than WBC alone (0.859 vs 0.710, P=0.010), with improved accuracy and sensitivity. In the validation set, the AUC of the combined model remained higher than that of WBC, but the difference was not statistically significant (0.728 vs 0.584, P=0.173). NRI analysis indicated that the combined model improved the correct classification of HCA by 25.0% (P=0.012) compared to that of WBC alone. DCA demonstrated that the combined model had a higher net benefit than WBC in most cases. The nomograms and web version of the model provided convenient tools for clinicians to predict the risk of HCA. Conclusion This study successfully developed and validated a clinically feasible multivariable model to predict the risk of HCA in women with late preterm and term PROM.
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Affiliation(s)
- Xinshui Wang
- Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
| | - Zheren Huang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
| | - Yan Ma
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
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14
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VALENTINE GREGORYC, WALLEN LINDAD. Neonatal Bacterial Sepsis and Meningitis. AVERY'S DISEASES OF THE NEWBORN 2024:439-449.e5. [DOI: 10.1016/b978-0-323-82823-9.00033-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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15
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Kumar KR, Shah SJ, Fayyad RM, Turla TM, O'Sullivan LM, Wallace B, Clark RH, Benjamin DK, Greenberg RG, Hornik CP. Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants. J Pediatric Infect Dis Soc 2023; 12:S28-S36. [PMID: 38146863 DOI: 10.1093/jpids/piad067] [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: 06/20/2023] [Accepted: 09/08/2023] [Indexed: 12/27/2023]
Abstract
BACKGROUND We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). METHODS We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies. We performed subgroup analysis in EOS episodes caused by Gram-negative and Gram-positive organisms. RESULTS Of the 62,178 infants and 64,559 cultures that met study inclusion criteria, 739 (1%) cultures were positive. The median (25th, 75th percentile) glucose value was 75 mg/dL (50, 106) on the day of or day prior to a positive culture versus 70 mg/dL (50, 95) on the day of or day prior to a negative culture. We found that hypoglycemia was not associated with the occurrence of EOS for all organisms and Gram-positive organisms, whereas there was a small but significant association between the lower AAP glucose cutoff value and EOS due to Gram-negative organisms (logistic regression: risk difference [RD] 0.24% [95% CI, 0.01-0.47]; IPW: RD 0.22% [95% CI, 0.00-0.43]). CONCLUSIONS Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia.
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Affiliation(s)
- Karan R Kumar
- Department of Pediatrics, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Sonam J Shah
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Rawan M Fayyad
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Toby M Turla
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Laura M O'Sullivan
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Beatriz Wallace
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Reese H Clark
- Pediatrix Center for Research, Education, Quality, and Safety, Sunrise, Florida, USA
| | - Daniel K Benjamin
- Department of Pediatrics, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Rachel G Greenberg
- Department of Pediatrics, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
| | - Christoph P Hornik
- Department of Pediatrics, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Duke University, Durham, North Carolina, USA
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16
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Aeimcharnbanchong K. Incidence Rate and Associated Factors of Early Onset Sepsis Among Neonate Born at ≥35 Weeks' Gestation in Thai Tertiary Hospital. Infect Drug Resist 2023; 16:4093-4100. [PMID: 37396069 PMCID: PMC10312319 DOI: 10.2147/idr.s415590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/21/2023] [Indexed: 07/04/2023] Open
Abstract
Purpose This study aimed to find the incidence rate and associated factors of EOS in neonates with 35 weeks of gestational age or more at Panyananthaphikkhu Chonprathan Medical Center (PCMC) in order to develop effective prevention and treatment strategies to reduce neonatal mortality. Methods A cross-sectional study was done in a single-center neonatal intensive care unit at PCMC. Data were collected from October 2016 to September 2021 from all neonates with 35 weeks of gestational age or more with EOS and randomly collected from neonates with 35 weeks of gestational age or more without EOS. The associated factors of EOS were shown as an odds ratio by multivariate analysis of binary logistic regression. Results In this study, 595 neonates were enrolled and divided into 2 groups - EOS group (193 neonates) and non-EOS group (402 neonates). The incidence rate of EOS was 21.23/1000 live births, comprising 2 culture-positive EOS neonates (0.22/1000 live births) and 191 culture-negative EOS neonates (21/1000 live births). The common clinical manifestations in the EOS group were respiratory distress (157 neonates, 81%), temperature instability (43 neonates, 22.3%) and poor feeding (39 neonates, 20.2%). Statistically significant relationship (p-value < 0.05) was found in prolonged rupture of membrane (OR 11.7, 95% CI: 2.54-53.88), low birth weight (OR 2.3, 95% CI: 1.25-4.4) and normal Apgar score at 5 minutes after birth (OR 0.5, 95% CI: 0.31-0.71). Conclusion Our study shows that the incidence rate of culture positive EOS in late preterm and term is very low. EOS was significantly associated with prolonged rupture of membrane and low birth weight whereas lower rate of EOS was significantly associated with normal Apgar score at 5 minutes after birth. Efforts to recognize these factors early and effectively resuscitate neonates may reduce and prevent neonatal morbidity and mortality.
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Affiliation(s)
- Kanokwan Aeimcharnbanchong
- Department of Pediatrics, Panyananthaphikkhu Chonprathan Medical Center, Srinakarinwirot University, Nonthaburi, Thailand
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17
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Mekic N, Selimovic A, Cosickic A, Mehmedovic M, Hadzic D, Zulic E, Mustafic S, Serak A. Predictors of adverse short-term outcomes in late preterm infants. BMC Pediatr 2023; 23:298. [PMID: 37328827 PMCID: PMC10276478 DOI: 10.1186/s12887-023-04112-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 06/05/2023] [Indexed: 06/18/2023] Open
Abstract
BACKGROUND Infants born between 34 weeks and 36 weeks and 6 days of gestation are defined as late preterm infants (LPIs), and they account for approximately 74% of all premature births. Preterm birth (PB) remains the leading cause of infant mortality and morbidity worldwide. AIM To analyse short-term morbidity and mortality and identify predictors of adverse outcomes in late preterm infants. PATIENTS AND METHODS In this retrospective study, we evaluated adverse short-term outcomes of LPIs admitted to the Intensive Care Unit (ICU), Clinic for Children's Diseases, University Clinical Center Tuzla, between 01.01.2020 and 31.12.2022. The analysed data included sex, gestational age, parity, birth weight, Apgar score (i.e., assessment of vitality at birth in the first and fifth minutes after birth), and length of hospitalization in NICU, as well as short-term outcome data. Maternal risk factors we observed were: age of mother, parity, maternal morbidity during pregnancy, complications and treatment during pregnancy. LPIs with major anatomic malformations were excluded from the study. Logistic regression analysis was used to identify risk factors for neonatal morbidity among LPIs. RESULTS We analysed data from 154 late preterm newborns, most of whom were male (60%), delivered by caesarean Sect. (68.2%) and from nulliparous mothers (63.6%). Respiratory complications were the most common outcome among all subgroups, followed by CNS morbidity, infections and jaundice requiring phototherapy. The rate of almost all of the complications in the late-preterm group decreased as gestational age increased from 34 to 36 weeks. Birth weight (OR: 1,2; 95% CI: 0,9 - 2,3; p = 0,0313) and male sex (OR: 2,5; 95% CI: 1,1-5,4; p = 0,0204) were significantly and independently associated with an increased risk for respiratory morbidity, and gestational weeks and male sex were associated with infectious morbidity. None of the risk factors analysed herein were predictors of CNS morbidity in LPIs. CONCLUSION A younger gestational age at birth is associated with a greater risk of short-term complications among LPIs, thus highlighting the need for increased knowledge about the epidemiology of these late preterm births. Understanding the risks of late preterm birth is critical to optimizing clinical decision-making, enhancing the cost-effectiveness of endeavours to delay delivery during the late preterm period, and reducing neonatal morbidity.
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Affiliation(s)
- Nina Mekic
- Pediatric Department, Health and Educational Medical Center Tuzla, Tuzla, Bosnia and Herzegovina.
| | - Amela Selimovic
- Clinic for Children's Diseases Tuzla, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Almira Cosickic
- Clinic for Children's Diseases Tuzla, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Majda Mehmedovic
- Clinic for Internal Medicine, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Devleta Hadzic
- Clinic for Children's Diseases Tuzla, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Evlijana Zulic
- Clinic for Children's Diseases Tuzla, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Sehveta Mustafic
- Polyclinic for Laboratory Diagnostics University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Amra Serak
- Pediatric Department, Health and Educational Medical Center Tuzla, Tuzla, Bosnia and Herzegovina
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18
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Marsh MC, Lin HM, Black J, Allen K, Weiner B, Ramilo O, Klamer B, Watson JR, Kasick R. Preterm and Term Infants Evaluated for Sepsis: Differences in Management and Clinical Outcomes. Hosp Pediatr 2023; 13:544-554. [PMID: 37222075 DOI: 10.1542/hpeds.2022-007050] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
BACKGROUND AND OBJECTIVES To describe differences in practice patterns and outcomes of young preterm versus age-matched term infants evaluated for sepsis, because evaluation and management of this group are not well defined. METHODS We conducted a retrospective single-center study at an academic, freestanding children's hospital of previously healthy preterm and term infants aged 0 to 60 days, who presented for initial evaluation of fever and/or hypothermia from 2014 to 2019. We classified infants by gestational age as preterm (32-36 6/7 weeks) and term (37-42 weeks) and compared diagnostic evaluation, management, and clinical outcomes. RESULTS Out of 363 preterm infants evaluated for sepsis, 336 met inclusion criteria; within the same study period, 2331 term infants were evaluated for sepsis, of which 600 were randomly selected and 554 were included. Clinicians performed inflammatory marker testing and chest x-rays more frequently in preterm infants 31% vs 25% (P = .034) and 50% vs 32% (P < .001), respectively. Preterm infants had a higher rate of bacteremia 5.9% vs 2.5% (P = .035), were hospitalized more frequently 72% vs 63% (P = .006), and required ICU level of care more often 32% vs 5% (P < .001) than term infants. They had lower rates of viral infections 33% vs 42% (P = .015) and no significant increased return visits. Febrile preterm and term infants, and older hypothermic preterm infants had relatively higher rates of serious bacterial infections. Hypothermic preterm infants had the longest hospitalizations. CONCLUSIONS Preterm infants had increased rates of bacteremia and required higher level of care compared with age-matched term infants, likely reflecting their increased risk for sepsis and other concomitant morbidities associated with preterm birth.
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Affiliation(s)
| | | | - Joshua Black
- Nationwide Children's Hospital, Columbus, Ohio
- The Ohio State University, College of Medicine, Columbus, Ohio
| | - Karen Allen
- Nationwide Children's Hospital, Columbus, Ohio
| | - Benjamin Weiner
- The Ohio State University, College of Medicine, Columbus, Ohio
| | - Octavio Ramilo
- Nationwide Children's Hospital, Columbus, Ohio
- The Ohio State University, College of Medicine, Columbus, Ohio
| | - Brett Klamer
- Nationwide Children's Hospital, Columbus, Ohio
- The Ohio State University, College of Medicine, Columbus, Ohio
| | - Joshua R Watson
- Nationwide Children's Hospital, Columbus, Ohio
- The Ohio State University, College of Medicine, Columbus, Ohio
| | - Rena Kasick
- Nationwide Children's Hospital, Columbus, Ohio
- The Ohio State University, College of Medicine, Columbus, Ohio
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19
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Brachio SS, Gu W, Saiman L. Next Steps for Health Care-Associated Infections in the Neonatal Intensive Care Unit. Clin Perinatol 2023; 50:381-397. [PMID: 37201987 DOI: 10.1016/j.clp.2023.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
We discuss the burden of health care-associated infections (HAIs) in the neonatal ICU and the role of quality improvement (QI) in infection prevention and control. We examine specific QI opportunities and approaches to prevent HAIs caused by Staphylococcus aureus , multidrug-resistant gram-negative pathogens, Candida species, and respiratory viruses, and to prevent central line-associated bloodstream infections (CLABSIs) and surgical site infections. We explore the emerging recognition that many hospital-onset bacteremia episodes are not CLABSIs. Finally, we describe the core tenets of QI, including engagement with multidisciplinary teams and families, data transparency, accountability, and the impact of larger collaborative efforts to reduce HAIs.
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Affiliation(s)
- Sandhya S Brachio
- Division of Neonatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, 622 West 168th Street, PH17, New York, NY 10032, USA.
| | - Wendi Gu
- Division of Neonatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, 622 West 168th Street, PH17, New York, NY 10032, USA
| | - Lisa Saiman
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, 622 West 168th Street, PH1-470, New York, NY 10032, USA; Department of Infection Prevention and Control, NewYork-Presbyterian Hospital, New York, NY, USA
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20
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But Š, Celar B, Fister P. Tackling Neonatal Sepsis-Can It Be Predicted? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3644. [PMID: 36834338 PMCID: PMC9959311 DOI: 10.3390/ijerph20043644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/11/2023] [Accepted: 02/16/2023] [Indexed: 06/18/2023]
Abstract
(1) Background: Early signs of sepsis in a neonate are often subtle and non-specific, the clinical course rapid and fulminant. The aim of our research was to analyse diagnostic markers for neonatal sepsis and build an application which could calculate its probability. (2) Methods: A retrospective clinical study was conducted on 497 neonates treated at the Clinical Department of Neonatology of the University Children's Hospital in Ljubljana from 2007 to 2021. The neonates with a diagnosis of sepsis were separated based on their blood cultures, clinical and laboratory markers. The influence of perinatal factors was also observed. We trained several machine-learning models for prognosticating neonatal sepsis and used the best-performing model in our application. (3) Results: Thirteen features showed highest diagnostic importance: serum concentrations of C-reactive protein and procalcitonin, age of onset, immature neutrophil and lymphocyte percentages, leukocyte and thrombocyte counts, birth weight, gestational age, 5-min Apgar score, gender, toxic changes in neutrophils, and childbirth delivery. The created online application predicts the probability of sepsis by combining the data values of these features. (4) Conclusions: Our application combines thirteen most significant features for neonatal sepsis development and predicts the probability of sepsis in a neonate.
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Affiliation(s)
- Špela But
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Brigita Celar
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Petja Fister
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Paediatric Intensive Care, Division of Paediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
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21
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Jansen SJ, Ree IMC, Broer L, de Winter D, de Haas M, Bekker V, Lopriore E. Neonatal sepsis in alloimmune hemolytic disease of the fetus and newborn: A retrospective cohort study of 260 neonates. Transfusion 2023; 63:117-124. [PMID: 36334304 PMCID: PMC10099948 DOI: 10.1111/trf.17176] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/30/2022] [Accepted: 10/13/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period. STUDY DESIGN AND METHODS All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated. Numbers of confirmed and suspected early- and late-onset sepsis episodes were assessed over the entire study period. RESULTS Of the 260 included infants, 25 (9.6%) were evaluated for suspected sepsis, with 16 (6.2%) having ≥1 confirmed sepsis episode. A total of 123 central-lines were placed in 98 (37.7%) neonates, with impending exchange transfusion (ET) being the most frequent indication. Of the 34 (34.7%) neonates in whom a central-line was placed due to impending ET, 11 (32.4%) received no ET. Overall CLABSI incidence was 13.58 per 1000 central-line days. Neonates with a central-line had a higher risk for confirmed late-onset infection (RR 1.11, 95% CI: 1.04-1.20) and sepsis work-up (RR 1.10, 95% CI: 1.03-1.17) compared to infants without a central-line. CONCLUSIONS Sepsis incidence among neonates with HDFN remains high, in particular in those with a central-line. Considering the substantial proportion of neonates with a central-line without eventual ET, central-line placement should be delayed until the likelihood of ET is high.
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Affiliation(s)
- Sophie J Jansen
- Division of Neonatology, Department of Pediatrics, Willem Alexander Children's Hospital, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Isabelle M C Ree
- Division of Neonatology, Department of Pediatrics, Willem Alexander Children's Hospital, Leiden University Medical Center (LUMC), Leiden, The Netherlands.,Department of Hematology, Center for Clinical Transfusion Research, Amsterdam, The Netherlands
| | - Lana Broer
- Division of Neonatology, Department of Pediatrics, Willem Alexander Children's Hospital, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Derek de Winter
- Division of Neonatology, Department of Pediatrics, Willem Alexander Children's Hospital, Leiden University Medical Center (LUMC), Leiden, The Netherlands.,Department of Hematology, Center for Clinical Transfusion Research, Amsterdam, The Netherlands
| | - Masja de Haas
- Department of Hematology, Center for Clinical Transfusion Research, Amsterdam, The Netherlands
| | - Vincent Bekker
- Division of Neonatology, Department of Pediatrics, Willem Alexander Children's Hospital, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Enrico Lopriore
- Division of Neonatology, Department of Pediatrics, Willem Alexander Children's Hospital, Leiden University Medical Center (LUMC), Leiden, The Netherlands
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22
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Debnath S, Koppel R, Saadi N, Potak D, Weinberger B, Zanos TP. Prediction of intrapartum fever using continuously monitored vital signs and heart rate variability. Digit Health 2023; 9:20552076231187594. [PMID: 37448783 PMCID: PMC10336767 DOI: 10.1177/20552076231187594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 06/23/2023] [Indexed: 07/15/2023] Open
Abstract
Objectives Neonatal early onset sepsis (EOS), bacterial infection during the first seven days of life, is difficult to diagnose because presenting signs are non-specific, but early diagnosis before birth can direct life-saving treatment for mother and baby. Specifically, maternal fever during labor from placental infection is the strongest predictor of EOS. Alterations in maternal heart rate variability (HRV) may precede development of intrapartum fever, enabling incipient EOS detection. The objective of this work was to build a predictive model for intrapartum fever. Methods Continuously measured temperature, heart rate, and beat-to-beat RR intervals were obtained from wireless sensors on women (n = 141) in labor; traditional manual vital signs were taken every 3-6 hours. Validated measures of HRV were calculated in moving 5-minute windows of RR intervals: standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD) between normal heartbeats. Results Fever (>38.0 °C) was detected by manual or continuous measurements in 48 women. Compared to afebrile mothers, average SDNN and RMSSD in febrile mothers decreased significantly (p < 0.001) at 2 and 3 hours before fever onset, respectively. This observed HRV divergence and raw recorded vitals were applied to a logistic regression model at various time horizons, up to 4-5 hours before fever onset. Model performance increased with decreasing time horizons, and a model built using continuous vital signs as input variables consistently outperformed a model built from episodic vital signs. Conclusions HRV-based predictive models could identify mothers at risk for fever and infants at risk for EOS, guiding maternal antibiotic prophylaxis and neonatal monitoring.
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Affiliation(s)
- Shubham Debnath
- Institute of Health System Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA
| | - Robert Koppel
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Neonatal-Perinatal Medicine, Cohen Children's Medical Center, Queens, NY, USA
| | - Nafeesa Saadi
- Neonatal-Perinatal Medicine, Cohen Children's Medical Center, Queens, NY, USA
| | - Debra Potak
- Neonatal-Perinatal Medicine, Cohen Children's Medical Center, Queens, NY, USA
| | - Barry Weinberger
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Neonatal-Perinatal Medicine, Cohen Children's Medical Center, Queens, NY, USA
| | - Theodoros P Zanos
- Institute of Health System Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
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23
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Neonatal Disease Prediction Using Machine Learning Techniques. JOURNAL OF HEALTHCARE ENGINEERING 2023; 2023:3567194. [PMID: 36875748 PMCID: PMC9981287 DOI: 10.1155/2023/3567194] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 01/04/2023] [Accepted: 02/09/2023] [Indexed: 02/25/2023]
Abstract
Neonatal diseases are among the main causes of morbidity and a significant contributor to underfive mortality in the world. There is an increase in understanding of the pathophysiology of the diseases and the implementation of different strategies to minimize their burden. However, improvements in outcomes are not adequate. Limited success is due to different factors, including the similarity of symptoms, which can lead to misdiagnosis, and the inability to detect early for timely intervention. In resource-limited countries like Ethiopia, the challenge is more severe. Low access to diagnosis and treatment due to the inadequacy of neonatal health professionals is one of the shortcomings. Due to the shortage of medical facilities, many neonatal health professionals are forced to decide the type of disease only based on interviews. They may not have a complete picture of all variables that have a contributing effect on neonatal disease from the interview. This can make the diagnosis inconclusive and may lead to a misdiagnosis. Machine learning has great potential for early prediction if relevant historical data is available. We have applied a classification stacking model for the following four main neonatal diseases: sepsis, birth asphyxia, necrotizing enter colitis (NEC), and respiratory distress syndrome. These diseases account for 75% of neonatal deaths. The dataset has been obtained from the Asella Comprehensive Hospital. It has been collected between 2018 and 2021. The developed stacking model was compared to three related machine-learning models XGBoost (XGB), Random Forest (RF), and Support Vector Machine (SVM). The proposed stacking model outperformed the other models, with an accuracy of 97.04%. We believe that this will contribute to the early detection and accurate diagnosis of neonatal diseases, especially for resource-limited health facilities.
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24
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Powell JM, Frank ZC, Clark GV, Lo JO, Caughey AB. Expectant management of preterm premature rupture of membranes at 34 weeks: a cost effectiveness analysis. J Matern Fetal Neonatal Med 2022; 35:9136-9144. [PMID: 34915811 PMCID: PMC10148142 DOI: 10.1080/14767058.2021.2017874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/01/2021] [Accepted: 12/08/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE To examine the outcomes and cost effectiveness of expectant management versus immediate delivery of women who experience preterm premature rupture of membranes (PPROM) at 34 weeks. METHODS A cost-effectiveness model was built using TreeAge software to compare outcomes in a theoretical cohort of 37,455 women with PPROM at 34 weeks undergoing expectant management until 37 weeks versus immediate delivery. Outcomes included fetal death, neonatal sepsis, neonatal death, neonatal neurodevelopmental delay, healthy neonate, maternal sepsis, maternal death, cost, and quality-adjusted life years. Probabilities were derived from the literature, and a cost-effectiveness threshold was set at $100,000 per quality-adjusted life year. RESULTS In our theoretical cohort of 37,455 women, expectant management yielded 58 fewer neonatal deaths and 164 fewer cases of neonatal neurodevelopmental delay. However, it resulted in 407 more cases of neonatal sepsis and 2.7 more cases of maternal sepsis. Expectant management resulted in 3,531 more quality-adjusted life years and a cost savings of $71.9 million per year, making it a dominant strategy. Univariate sensitivity analysis demonstrated expectant management was cost effective until the weekly cost of antepartum admission exceeded $17,536 (baseline estimate: $12,520) or the risk of maternal sepsis following intraamniotic infection exceeded 20%. CONCLUSION Our model demonstrated that expectant management of PPROM at 34 weeks yielded better outcomes on balance at a lower cost than immediate delivery. This analysis is important and timely in light of recent studies suggesting improved neonatal outcomes with expectant management. However, individual risks and preferences must be considered in making this clinical decision as expectant management may increase the risk of adverse perinatal outcomes when the risk of puerperal infection increases.
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Affiliation(s)
- Jacqueline M Powell
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Zoë C Frank
- Department of Obstetrics & Gynecology, Creighton University Arizona Health Education Alliance, Phoenix, AZ, USA
| | - Grace V Clark
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Jamie O Lo
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Aaron B Caughey
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
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25
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Abstract
Infections by meningococcal species are extremely rare in the first days of life. We present a fatal case of early-onset sepsis presenting at birth, caused by intrauterine transmission of serogroup Y N. meningitidis, evidenced clinically and histologically by corresponding chorioamnionitis and N. meningitidis-positive amniotic fluid. This case confirms a long-standing suspicion that N. meningitidis can be transmitted in utero.
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26
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Barak-Corren Y, Elizur Y, Yuval S, Burstyn A, Deri N, Schwartz S, Megged O, Toker O. The risk of serious bacterial infections among young ex-premature infants with fever. Front Pediatr 2022; 10:1021007. [PMID: 36313886 PMCID: PMC9597199 DOI: 10.3389/fped.2022.1021007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 09/22/2022] [Indexed: 11/13/2022] Open
Abstract
Background and Objectives To determine the rate of serious-bacterial-infections (SBI) in young ex-premature infants with fever, and to develop a risk-stratification algorithm for these patients. Methods A retrospective cohort study including all infants who presented to the pediatric emergency department (ED) of a tertiary-care university-hospital between 2010 and 2020 with fever (≥38°C), were born prematurely (<37-weeks), had post-conception age of <52-weeks, and had available blood, urine, or CSF cultures. The rates of SBI by age-of-birth and age-at-visit were calculated and compared to a cohort of matched full-term controls. Results The study included a total of 290 ex-premature cases and 290 full-term controls. There were 11 cases (3.8%) with an invasive bacterial infection (IBI) of either bacteremia, meningitis or both and only six controls (2.1%) with IBI (p = 0.32). Over 28-days chronologic-age, there were 10 (3.6%) IBIs among cases and no IBIs among the controls (p = 0.02). There were eight (3%) cases and three (1%) controls with IBI who were well-appearing on physical examination (p = 0.19). All eight well-appearing ex-premature infants were under 60-days adjusted-age, seven of whom (88%) were also under 28-days adjusted-age. There were 28 (10.6%) cases and 34 (12%) controls with urinary tract infection (UTI) (p = 0.5). Among cases under 60-days adjusted-age, urinalysis was not reliable to exclude UTI (50% negative). Conclusions Well-appearing ex-preterm infants have a significant risk for IBI until the adjusted age of 28-days and for UTI until the adjusted age of 60-days. Further studies are needed to evaluate the approach to fever in this unique population.
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Affiliation(s)
- Yuval Barak-Corren
- The Pediatrics Department, Shaare Zedek Medical Center, Jerusalem, Israel
- Predictive Medicine Group, Boston Children's Hospital, Boston, United States
| | - Yoav Elizur
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Shira Yuval
- The Pediatrics Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Amalia Burstyn
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Noy Deri
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Shepard Schwartz
- The Pediatric Emergency Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Orli Megged
- The Pediatrics Department, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- The Pediatric Infectious Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ori Toker
- The Pediatrics Department, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- The Allergy and Clinical Immunology Unit, Shaare Zedek Medical Center, Jerusalem, Israel
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Abstract
Clinical Decision Support (CDS) tools help the healthcare team diagnose, monitor, and treat patients more efficiently and consistently by executing clinical practice guidelines and recommendations. As a result, CDS has a direct impact on the delivery and healthcare outcomes. This review covers the fundamental concepts, as well as the infrastructure needed to create a CDS tool and examples of its use in the neonatal setting. This article also serves as a primer on what to think about when proposing the development of a new CDS tool, or when upgrading an existing one. We also highlight important elements that influence CDS development, such as informatics methodologies, data and device interoperability, and regulation.
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Affiliation(s)
- Anoop Rao
- Stanford University School of Medicine, Center for Academic Medicine, # 434A, 453 Quarry Rd, Palo Alto, CA, 94304, USA.
| | - Jonathan Palma
- Orlando Health Winnie Palmer Hospital for Women and Babies, 83 W Miller St, Orlando, FL, 32806, USA.
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28
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Miselli F, Cuoghi Costantini R, Creti R, Sforza F, Fanaro S, Ciccia M, Piccinini G, Rizzo V, Pasini L, Biasucci G, Pagano R, Capretti M, China M, Gambini L, Pulvirenti RM, Dondi A, Lanari M, Pedna M, Ambretti S, Lugli L, Bedetti L, Berardi A. Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis. Microorganisms 2022; 10:1878. [PMID: 36296155 PMCID: PMC9607315 DOI: 10.3390/microorganisms10101878] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/06/2022] [Accepted: 09/16/2022] [Indexed: 11/17/2022] Open
Abstract
The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00-0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00-0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02-0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics.
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Affiliation(s)
- Francesca Miselli
- Neonatal Intensive Care Unit, Women’s and Children’s Health Department, University Hospital of Modena, 41124 Modena, Italy
| | - Riccardo Cuoghi Costantini
- Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Roberta Creti
- Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Francesca Sforza
- Pediatric Post-Graduate School, University of Modena e Reggio Emilia, 41125 Modena, Italy
| | - Silvia Fanaro
- Department of Medical Sciences, Pediatric Section, University of Ferrara, 44124 Ferrara, Italy
| | - Matilde Ciccia
- Neonatal Intensive Care Unit, Women’s and Children’s Health Department, Maggiore Hospital, 40133 Bologna, Italy
| | | | - Vittoria Rizzo
- Neonatal Intensive Care Unit, Bufalini Hospital of Cesena, 47521 Cesena, Italy
| | - Lorena Pasini
- Department of Paediatric Anaesthesia and Intensive Care, S.Orsola-Malpighi Hospital, 40138 Bologna, Italy
| | - Giacomo Biasucci
- Pediatric and Neonatal Unit, Women’s and Children’s Health Department, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
| | | | - Mariagrazia Capretti
- Neonatal Intensive Care Unit, Women’s and Children’s Health Department, S.Orsola-Malpighi Hospital, 40138 Bologna, Italy
| | | | - Lucia Gambini
- Neonatal Intensive Care Unit, University Hospital of Parma, 43126 Parma, Italy
| | - Rita Maria Pulvirenti
- Pediatric and Neonatal Unit, Morgagni-Pierantoni Hospital of Forlì, 47121 Forlì, Italy
| | - Arianna Dondi
- Pediatric Emergency Unit, Scientific Institute for Research and Healthcare (IRCCS), Sant’Orsola Hospital, 40138 Bologna, Italy
| | - Marcello Lanari
- Pediatric Emergency Unit, Scientific Institute for Research and Healthcare (IRCCS), Sant’Orsola Hospital, 40138 Bologna, Italy
| | | | - Simone Ambretti
- Unit of Clinical Microbiology, Scientific Institute for Research and Healthcare (IRCCS), Sant’Orsola Hospital, 40138 Bologna, Italy
| | - Licia Lugli
- Neonatal Intensive Care Unit, Women’s and Children’s Health Department, University Hospital of Modena, 41124 Modena, Italy
| | - Luca Bedetti
- Neonatal Intensive Care Unit, Women’s and Children’s Health Department, University Hospital of Modena, 41124 Modena, Italy
- PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Alberto Berardi
- Neonatal Intensive Care Unit, Women’s and Children’s Health Department, University Hospital of Modena, 41124 Modena, Italy
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29
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Trollfors B, Melin F, Gudjonsdottir MJ, Rupröder R, Sandin M, Dahl M, Karlsson J, Backhaus E. Group B streptococcus — a pathogen not restricted to neonates. IJID REGIONS 2022; 4:171-175. [PMID: 36059918 PMCID: PMC9434026 DOI: 10.1016/j.ijregi.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 08/03/2022] [Indexed: 12/04/2022]
Abstract
Invasive group B streptococcal (GBS) infections can occur in any age group, not only neonates. Most of the patients are elderly or have severe concomitant diseases. Screening-based intrapartum antibiotic prophylaxis (based on maternal risk factors) significantly decreases very early-onset infections. Objectives This was a retropective study of invasive group B streptococcal (GBS) infections isolated from blood, cerebrospinal fluid (CSF), synovial fluid, peritoneal fluid, pleural fluid, pericardial fluid and corpus vitreum in a defined region in southwest Sweden over a 14-year period. Design Information on all invasive GBS infections was obtained from all four bacteriological laboratories in the region, with data obtained from individual patient records. Results GBS was isolated from normally sterile body fluids in 1244 samples (579 from females and 665 from males) from 1101 patients. Of these patients, 196 were neonates. The incidence in neonates (0–27 days) was 7.3 per 100 000 live births per year, but there was a significant decrease from 2012 when risk-factor-based intrapartum antibibiotic prophylaxis was implemented. The great majority of neonatal infections were very early-onset infections. The incidence rates in children (28 days to 17 years), adults (18–64 years) and elderly patients (≥ 65 years) were 1.3, 3.6, and 12.9 per 100 000 per year, respectively. The majority of children and adults had severe underlying diseases, but severe infections were also seen in individuals with no risk factors. Conclusions GBS is an important pathogen in all age groups. Intrapartum antibiotic prophylaxis significantly decreases very early-onset infections.
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Affiliation(s)
- Birger Trollfors
- Department of Pediatrics, Sahlgrenska University Hospital, Gothenburg, Sweden and University of Gothenburg, Gothenburg, Sweden
- Corresponding author: Dr Birger Trollfors, Department of Pediatrics, Sahlgrenska University Hospital SE-41685, Gothenburg, Sweden
| | - Fredrik Melin
- Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden
| | - Margret Johansson Gudjonsdottir
- Department of Pediatrics, Sahlgrenska University Hospital, Gothenburg, Sweden and University of Gothenburg, Gothenburg, Sweden
| | - Rebecca Rupröder
- Department of Pediatrics, South Älvsborg Hospital, Borås, Sweden
| | - Milen Sandin
- Department of Pediatrics, South Älvsborg Hospital, Borås, Sweden
| | - Mats Dahl
- Department of Medicine, Kungälv Hospital, Kungälv, Sweden
| | - Johanna Karlsson
- Department of Infectious Diseases, NU Hospital Group, Trollhättan, Sweden
| | - Erik Backhaus
- Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden
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30
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Blood pressure, organ dysfunction, and mortality in preterm neonates with late-onset sepsis. Pediatr Res 2022; 92:498-504. [PMID: 34671093 DOI: 10.1038/s41390-021-01768-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/18/2021] [Accepted: 09/20/2021] [Indexed: 11/08/2022]
Abstract
BACKGROUND The objective of this study was to investigate the association between systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP) and adverse outcomes in preterm neonates with late-onset sepsis (LOS). METHODS This is a two-center retrospective study over 6 years. Neonates <35 weeks gestational age (GA) with blood ± cerebrospinal fluid culture positive for organisms other than coagulase-negative Staphylococcus at >72 h age were included. Outcome measures were organ dysfunction (ODF) using the predefined criteria and post-ODF mortality (≤7 days from LOS onset). The lowest noninvasive blood pressures (BPs) recorded at baseline (24-48 h pre-LOS) and 0-12, 13-24, 25-36, and 37-48 h post LOS were analyzed. RESULTS Of 147 neonates, ODF occurred in 70 (48%), of which 20 (29%) died. ODF was associated with a drop in all BP components, starting 0-12 h post-LOS onset (p < 0.01 for all); BPs remained unchanged in the non-ODF group. Mortality was associated with a greater reduction in SBP [-13 (-19, -8) vs. -4 (-8, 0); p < 0.01] and MBP [-9 (-13, -5) vs. +1 (-1, +4); p = 0.03] 0-12 h post-LOS onset. SBP had a higher area under the curve for mortality than MBP and DBP (0.83, 0.81, and 0.78, respectively). An inverse relation may exist between corrected GA and percentage reduction in SBP from baseline for equivalent risk of death. CONCLUSIONS Reduction in BPs early in illness may identify preterm neonates at the highest risk of ODF and mortality from LOS. IMPACT Drop in BPs from baseline starting in the immediate post-illness onset period may identify preterm neonates at the highest risk of developing ODF and mortality in LOS. Lowest systolic followed by mean BP measured during the first 12 h of illness provided the highest discriminating ability for LOS-related mortality. Absolute BPs recorded during the first 12 h of illness performed better than relative change from baseline for identifying neonates at risk of LOS-related mortality. The specific BP thresholds identified in this study may inform future therapeutic trials.
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Song WS, Park HW, Oh MY, Jo JY, Kim CY, Lee JJ, Jung E, Lee BS, Kim KS, Kim EAR. Neonatal sepsis-causing bacterial pathogens and outcome of trends of their antimicrobial susceptibility a 20-year period at a neonatal intensive care unit. Clin Exp Pediatr 2022; 65:350-357. [PMID: 34886592 PMCID: PMC9263424 DOI: 10.3345/cep.2021.00668] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/15/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Due to increases in the number of infants born with younger gestational age (GA) and lower birth weight, the incidence of neonatal sepsis is increasing. PURPOSE We investigated the changes in the prevalence of bacterial pathogens, their antimicrobial susceptibility, and sepsis-related mortality during 20 years at a neonatal intensive care unit. METHODS The study period was divided into two 10-year phases (1998-2007 vs. 2008-2017). Medical records were reviewed to gather data on demographics, causative microbial pathogens, incidence of multidrug-resistant organisms, antimicrobial susceptibility, and rates of sepsis-related mortality. RESULTS In both study phases, the most common pathogens for neonatal sepsis were coagulase-negative Staphylococcus (CoNS) (28.6%) and Enterobacter cloacae (16.1%) for early-onset sepsis (EOS, ≤72 hours after birth) and CoNS (54.7%) and Staphylococcus aureus (12.9%) for late-onset sepsis (LOS, >72 hours after birth). CoNS and S. aureus showed 100% sensitivity to vancomycin in both phases. The susceptibility of S. aureus to oxacillin increased from 19.2% to 57.9% in phase II than phase I. K. pneumonia and E. cloacae showed increases in its susceptibility to gentamicin, cefotaxime and ceftriaxone in phase II than phase I. In both phases, the most common pathogens that caused sepsis-related death were K. pneumoniae (18.2%) and Pseudomonas aeruginosa (13.6%). Sepsis-related mortality rate was higher in infants with GA <37 weeks than those with GA over 37 weeks (P=0.016). In addition, the mortality rate of neonatal sepsis caused by gram-negative bacteria was significantly higher than that caused by gram-positive bacteria (P<0.001). CONCLUSIONS CoNS was the most common pathogen for EOS and LOS. While we found significant changes in antimicrobial sensitivities over time. GA below 37 weeks and gram-negative organisms are associated with mortality rate.
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Affiliation(s)
- Woo Sun Song
- Department of Medicine, Kyungpook National University, College of Medicine, Daegu, Korea
| | - Hye Won Park
- Department of Pediatrics, Konkuk University Medical Center, Seoul, Korea
| | - Moon Youn Oh
- Division of Neonatology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Young Jo
- Department of Pediatrics, Gyeongsang National University Hospital, Jinju, Korea
| | - Chae Young Kim
- Department of Pediatrics, Kyung Hee University School of Medicine, Seoul, Korea
| | | | - Euiseok Jung
- Division of Neonatology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Sop Lee
- Division of Neonatology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Soo Kim
- Division of Neonatology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Ellen Ai-Rhan Kim
- Division of Neonatology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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Flores-Maldonado O, González GM, Montoya A, Andrade A, Treviño-Rangel R, Donis-Maturano L, Tavares-Carreón F, Becerril-García MA. Dissemination of Gram-positive bacteria to the lung of newborn mice increases local IL-6 and TNFα levels in lethal bacteremia. Microbes Infect 2022; 24:104984. [DOI: 10.1016/j.micinf.2022.104984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 04/08/2022] [Accepted: 04/22/2022] [Indexed: 12/01/2022]
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Untargeted 1H-NMR Urine Metabolomic Analysis of Preterm Infants with Neonatal Sepsis. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12041932] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
One of the most critical medical conditions occurring after preterm birth is neonatal sepsis, a systemic infection with high rates of morbidity and mortality, chiefly amongst neonates hospitalized in Neonatal Intensive Care Units (NICU). Neonatal sepsis is categorized as early-onset sepsis (EOS) and late-onset sepsis (LOS) regarding the time of the disease onset. The accurate early diagnosis or prognosis have hurdles to overcome, since there are not specific clinical signs or laboratory tests. Herein, a need for biomarkers presents, with the goals of aiding accurate medical treatment, reducing the clinical severity of symptoms and the hospitalization time. Through nuclear magnetic resonance (NMR) based metabolomics, we aim to investigate the urine metabolomic profile of septic neonates and reveal those metabolites which could be indicative for an initial discrimination between the diseased and the healthy ones. Multivariate and univariate statistical analysis between NMR spectroscopic data of urine samples from neonates that developed EOS, LOS, and a healthy control group revealed a discriminate metabolic profile of septic newborns. Gluconate, myo-inositol, betaine, taurine, lactose, glucose, creatinine and hippurate were the metabolites highlighted as significant in most comparisons.
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Takassi OE, Atakouma YD, Desfrere L. Predictors of early-onset neonatal sepsis in premature newborns: Case-control study. Arch Pediatr 2022; 29:183-187. [PMID: 35094903 DOI: 10.1016/j.arcped.2022.01.013] [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: 04/26/2021] [Revised: 12/05/2021] [Accepted: 01/13/2022] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Early-onset neonatal sepsis (EOS) is difficult to diagnose clinically because the semiology of premature newborns is poor during the first days of life. This study aimed to identify predictive factors of EOS in neonates less than 37 weeks' gestational age in neonatal care at Louis Mourier Hospital, France. METHOD This was a case-control study of all newborns less than 37 weeks of gestational age diagnosed and managed for EOS from January 1 to December 31, 2019. The main parameters studied were demographic characteristics, risk factors, laboratory, and bacteriological characteristics. At the benchmarking level, the statistical tests used were the McNemar test for qualitative variables and the paired Student's t-test for quantitative variables. RESULTS A total of 50 mother-child pairs were included in this study (25 cases and 25 matched controls). The results showed a statistically significant relationship between the birth of a child with EOS and between a premature rupture of membranes of > 18 h (68% of cases vs. 36% of controls; p = 0.042); a positive culture of the placenta (p = 0.0002); C-reactive protein levels of > 6 mg/L (88% of cases vs. 20% of controls; p = 0.001); a procalcitonin level of > 0.6 ng/mL (72% of cases vs. 16% of controls; p = 0.001). Gram-negative bacteria including Escherichia coli (44.5%) and Haemophilus influenzae (14.8%) were the most common pathogens found. CONCLUSION The search for risk factors must be systematic and the clinic must remain at the center of the diagnostic approach.
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Affiliation(s)
- Ounoo Elom Takassi
- Service de Néonatologie, Hôpital Louis Mourier, AP-HP, 92700, Colombes, Université Paris Didérot, Paris, France; Département de Pédiatrie, Université de Lomé, Faculté des Sciences de la Santé, Lomé, Togo.
| | - Yawo Dzayisse Atakouma
- Département de Pédiatrie, Université de Lomé, Faculté des Sciences de la Santé, Lomé, Togo
| | - Luc Desfrere
- Service de Néonatologie, Hôpital Louis Mourier, AP-HP, 92700, Colombes, Université Paris Didérot, Paris, France
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Viability-Resolved Metagenomics Reveals Antagonistic Colonization Dynamics of Staphylococcus epidermidis Strains on Preterm Infant Skin. mSphere 2021; 6:e0053821. [PMID: 34523979 PMCID: PMC8550141 DOI: 10.1128/msphere.00538-21] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Preterm infants are at increased risk of infections caused by coagulase-negative staphylococci (CoNS) that colonize skin. Technical barriers in sequencing low-microbial-biomass skin swabs from preterm infants hinder attempts to gain a strain-level understanding of CoNS colonization dynamics within their developing skin microbiome. Here, the microbiome of five skin sites and available stool was studied from four preterm infants hospitalized over their first 2 months of life. We used propidium monoazide treatment of samples to enrich for the viable microbiome and metagenomic shotgun sequencing to resolve species and strains. The microbiome of different skin sites overlapped with each other, was dominated by the CoNS species Staphylococcus epidermidis and Staphylococcus capitis, and was distinct from stool. Species diversity on skin increased over time despite antibiotic exposure. Evidence of antagonism between the most common S. epidermidis strains, ST2 and ST59, included negative relationships for species correlation networks and in situ replication rates and that ST2 colonized skin earlier but was often replaced by ST59 over time. Experiments done with reference isolates showed that ST2 produced more biofilm than ST59 on plastic surfaces, which was reduced in mixed culture. We also discovered that a rare S. epidermidis strain, ST5, grew rapidly in stool in association with Stenotrophomonas maltophilia from a suspected episode of infection. Viability treatment of samples and moderate throughput shotgun sequencing provides strain-level information about CoNS colonization dynamics of preterm infant skin that ultimately might be exploited to prevent infections. IMPORTANCE The skin is a habitat for microbes that commonly infect preterm infants, but the use of sequencing for fine-scale study of the microbial communities of skin that develop in these infants has been limited by technical barriers. We treated skin swabs of preterm infants with a photoreactive dye that eliminates DNA from nonviable microbes and then sequenced the remaining DNA. We found that two strains of the most common species, Staphylococcus epidermidis, showed an antagonistic relationship on skin by cooccurring with different species, replicating fastest in different samples, and dominating skin sites at different times. Representatives of these strains also differed in their ability to stick to plastic surfaces—an important pathogenicity trait of this species. Our study shows the feasibility of gaining detailed information about strain colonization dynamics from this difficult-to-sequence body site of preterm infants, which might be used to guide novel approaches to prevent infections.
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Girlich D, Ouzani S, Emeraud C, Gauthier L, Bonnin RA, Le Sache N, Mokhtari M, Langlois I, Begasse C, Arangia N, Fournier S, Fortineau N, Naas T, Dortet L. Uncovering the novel Enterobacter cloacae complex species responsible for septic shock deaths in newborns: a cohort study. THE LANCET MICROBE 2021; 2:e536-e544. [DOI: 10.1016/s2666-5247(21)00098-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/26/2021] [Accepted: 04/16/2021] [Indexed: 11/30/2022] Open
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Ching NS, Buttery JP, Lai E, Steer AC, Standish J, Ziffer J, Daley AJ, Doherty R. Breastfeeding and Risk of Late-Onset Group B Streptococcal Disease. Pediatrics 2021; 148:peds.2020-049561. [PMID: 34385351 DOI: 10.1542/peds.2020-049561] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/16/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Group B Streptococcus (GBS) is a major contributor to neonatal sepsis worldwide. Late-onset group B Streptococcus disease (LOGBS) and its risk factors remain poorly understood. The isolation of GBS from breast milk has been described in cases of LOGBS. This potential association has raised concerns for mothers and clinicians regarding the safety of ongoing breastfeeding. In this study, we aimed to investigate whether exposure to breast milk is associated with increased risk of LOGBS. METHODS A case-control study of LOGBS was conducted across 4 hospital networks in Victoria, Australia, including the 2 major tertiary pediatric centers in the state, to evaluate 11 years of data (2007-2017). Cases were captured initially from microbiology databases and recaptured with International Classification of Diseases discharge coding. Each case patient was matched with 4 controls to assess feeding status. Patients were matched for chronological age, gestation, discharge status, recruitment site, and calendar year. RESULTS We identified 92 cases of LOGBS: 73 cases on initial capture and 76 cases on the recapture analysis. Case patients were matched with 368 controls: 4 controls to each patient. Seventy-two patients were exposed to breast milk at the time of LOGBS (78.3%), compared with 274 controls (74.5%; odds ratio 1.2 [95% confidence interval 0.7-2.3]). CONCLUSIONS Breastfeeding was not associated with increased risk of LOGBS. Breast milk should not be tested for GBS during a first episode of LOGBS.
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Affiliation(s)
- Natasha S Ching
- Departments of Infection and Immunity .,Department of Paediatrics, Monash University, Clayton, Victoria, Australia.,General Paediatrics, Monash Children's Hospital, Monash Health, Clayton, Victoria, Australia
| | - Jim P Buttery
- Departments of Infection and Immunity.,Department of Paediatrics, Monash University, Clayton, Victoria, Australia.,Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine.,Infection and Immunity, Murdoch Children's Research Institute, Parkville, Victoria, Australia
| | - Emily Lai
- Departments of Infection and Immunity.,Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia
| | - Andrew C Steer
- Infection and Immunity, Murdoch Children's Research Institute, Parkville, Victoria, Australia.,Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.,Department of General Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Jane Standish
- Infection and Immunity, Murdoch Children's Research Institute, Parkville, Victoria, Australia.,Department of General Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.,Department of Children's Services, University Hospital Geelong, Barwon Health, Geelong, Victoria, Australia
| | - Joel Ziffer
- Department of Paediatrics, Bendigo Health, Bendigo, Victoria, Australia
| | - Andrew J Daley
- Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.,Laboratory Services.,Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia
| | - Richard Doherty
- Departments of Infection and Immunity.,Department of Paediatrics, Monash University, Clayton, Victoria, Australia
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Fischer A, Mowrer MC, Shallat S, Walker L, Shallat J. Ensuring a Locally Tailored Response to Early Onset Sepsis Screening Meets or Exceeds the Performance of Published Approaches. Hosp Pediatr 2021; 10:877-883. [PMID: 32989003 DOI: 10.1542/hpeds.2020-0153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND Evaluation of well-appearing neonates for early-onset sepsis (EOS) remains controversial. Multiple risk stratification approaches are currently used for the evaluation of EOS. Our aim was to quantify and compare frequency of laboratory evaluation and empirical antibiotics between published and local EOS approaches. METHODS This retrospective cohort study included 8240 infants born ≥35 + 0/7 weeks' gestation at an institution from October 1, 2014, to March 1, 2018. Excluded from analysis were 156 patients who exhibited either major congenital anomalies or required antibiotics for surgical issues. A total of 1680 patient charts with risk factors for EOS were reviewed for further demographic data, clinical presentation, laboratory results, and probable recommendations from 4 EOS risk assessment approaches. RESULTS Laboratory evaluation recommendation was 7.1% for Centers for Disease Control and Prevention 2010 guidelines and local 2016 EOS algorithm, 6% for local 2019 EOS algorithm, and 5.9% for Kaiser Permanente neonatal EOS calculator (neonatal EOS calculator). Antibiotic recommendation was 6% for 2010 Centers for Disease Control and Prevention guidelines, 4.3% for neonatal EOS calculator, and 3.3% for local 2016 and 2019 EOS algorithms. CONCLUSIONS Of the 4 approaches reviewed, the local 2019 EOS algorithm and the neonatal EOS calculator were similar in recommending the lowest frequency of laboratory evaluation and the local 2016 and 2019 EOS algorithms had the lowest recommended antibiotic usage in this population.
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Affiliation(s)
- Ashley Fischer
- Department of Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, Illinois; .,Division of Neonatology, Children's Hospital of Illinois, Peoria, Illinois
| | - Michael Colin Mowrer
- Division of Pediatric Critical Care, University of Texas Southwestern, Dallas, Texas
| | - Shelly Shallat
- Department of Pediatrics, OSF Saint Francis Medical Center, Peoria, Illinois; and
| | - Lucas Walker
- Department of Pediatrics, Children's National Hospital, Washington, District of Columbia
| | - Jaclyn Shallat
- Department of Pediatrics, OSF Saint Francis Medical Center, Peoria, Illinois; and
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Exploring Clinically-Relevant Experimental Models of Neonatal Shock and Necrotizing Enterocolitis. Shock 2021; 53:596-604. [PMID: 31977960 DOI: 10.1097/shk.0000000000001507] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Neonatal shock and necrotizing enterocolitis (NEC) are leading causes of morbidity and mortality in premature infants. NEC is a life-threatening gastrointestinal illness, the precise etiology of which is not well understood, but is characterized by an immaturity of the intestinal barrier, altered function of the adaptive immune system, and intestinal dysbiosis. The complexities of NEC and shock in the neonatal population necessitate relevant clinical modeling using newborn animals that mimic the disease in human neonates to better elucidate the pathogenesis and provide an opportunity for the discovery of potential therapeutics. A wide variety of animal species-including rats, mice, piglets, and primates-have been used in developing experimental models of neonatal diseases such as NEC and shock. This review aims to highlight the immunologic differences in neonates compared with adults and provide an assessment of the advantages and drawbacks of established animal models of both NEC and shock using enteral or intraperitoneal induction of bacterial pathogens. The selection of a model has benefits unique to each type of animal species and provides individual opportunities for the development of targeted therapies. This review discusses the clinical and physiologic relevance of animal models and the insight they contribute to the complexities of the specific neonatal diseases: NEC and shock.
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40
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Sewell E, Roberts J, Mukhopadhyay S. Association of Infection in Neonates and Long-Term Neurodevelopmental Outcome. Clin Perinatol 2021; 48:251-261. [PMID: 34030812 PMCID: PMC8260078 DOI: 10.1016/j.clp.2021.03.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Perinatal and neonatal infection and associated inflammatory response may adversely affect brain development and lead to neurodevelopmental impairment. Factors that predict the risk of infection and subsequent adverse outcomes have been identified but substantial gaps remain in identifying mechanisms and interventions that can alter outcomes. This article describes the current epidemiology of neonatal sepsis, the pathogenesis of brain injury with sepsis, and the reported long-term neurodevelopment outcomes among survivors.
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Affiliation(s)
- Elizabeth Sewell
- Division of Neonatology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, 2015 Uppergate Drive, Office #318, Atlanta, GA 30322, USA
| | - Jessica Roberts
- Division of Neonatology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA
| | - Sagori Mukhopadhyay
- Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, 800 Spruce Street, 2nd Floor Cathcart Building, Newborn Medicine, Philadelphia, PA, USA.
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Ma'ayeh M, Haight P, Oliver EA, Landon MB, Rood KM. Timing of Repeat Cesarean Delivery for Women with a Prior Classical Incision. Am J Perinatol 2021; 38:529-534. [PMID: 33053596 DOI: 10.1055/s-0040-1718576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE This study aimed to compare neonatal outcomes for delivery at 36 weeks compared with 37 weeks in women with prior classical cesarean delivery (CCD). STUDY DESIGN This was a secondary analysis of the prospective observational cohort of the Eunice Kennedy National Institute for Child and Human Development's Maternal-Fetal Medicine Unit Network Cesarean Registry. Data on cases of repeat cesarean delivery (RCD) in the setting of a prior CCD were abstracted and used for analysis. This study compared outcomes of women who delivered at 360/7 to 366/7 versus 370/7 to 376/7 weeks. The primary outcome was a composite of adverse neonatal outcomes that included neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), hypoglycemia, mechanical ventilation, sepsis, length of stay ≥5 days, and neonatal death. A composite of maternal outcomes that included uterine rupture, blood transfusion, general anesthesia, cesarean hysterectomy, venous thromboembolism, maternal sepsis, intensive care unit admission, and surgical complications was also evaluated. RESULTS There were 436 patients included in the analysis. Women who delivered at 36 weeks (n = 176) were compared those who delivered at 37 weeks (n = 260). There were no differences in baseline characteristics. Delivery at 37 weeks was associated with a reduction in composite neonatal morbidity (24 vs. 34%, adjusted odds ratio [aOR] = 0.61 [0.31-0.94]), including a decrease in NICU admission rates (20 vs. 29%, aOR = 0.63 [0.40-0.99]), hospitalization ≥5 days (13 vs. 24%, aOR = 0.48 [0.29-0.8]), and RDS or TTN (9 vs. 19%, aOR = 0.43 [0.24-0.77]). There was no difference in adverse maternal outcomes (7 vs. 7%, aOR = 0.98 [0.46-2.09]). CONCLUSION Delivery at 37 weeks for women with a history of prior CCD is associated with a decrease in adverse neonatal outcomes, compared with delivery at 36 weeks. KEY POINTS · Classical cesarean section may have increased risk of uterine rupture in future pregnancies.. · This study compares outcomes of delivery at 370/7 to 376/7 versus 360/7 to 366/7 weeks.. · Delivery at 370/7 to 376/7 weeks was associated with decreased neonatal morbidity..
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Affiliation(s)
- Marwan Ma'ayeh
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Paulina Haight
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Emily A Oliver
- Department of Obstetrics and Gynecology, Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, Pennsylvania
| | - Mark B Landon
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Kara M Rood
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
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Kucova P, Kantor L, Fiserova K, Lasak J, Röderova M, Kolar M. Bacterial Pathogens and Evaluation of a Cut-Off for Defining Early and Late Neonatal Infection. Antibiotics (Basel) 2021; 10:278. [PMID: 33803288 PMCID: PMC7998728 DOI: 10.3390/antibiotics10030278] [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: 02/16/2021] [Revised: 03/04/2021] [Accepted: 03/07/2021] [Indexed: 12/02/2022] Open
Abstract
Bacterial infections are an important cause of mortality and morbidity in newborns. The main risk factors include low birth weight and prematurity. The study identified the most common bacterial pathogens causing neonatal infections including their resistance to antibiotics in the Neonatal Department of the University Hospital Olomouc. Additionally, the cut-off for distinguishing early- from late-onset neonatal infections was assessed. The results of this study show that a cut-off value of 72 h after birth is more suitable. Only in case of early-onset infections arising within 72 h of birth, initial antibiotic therapy based on gentamicin with ampicillin or amoxicillin/clavulanic acid may be recommended. It has been established that with the 72-h cut-off, late-onset infections caused by bacteria more resistant to antibiotics may be detected more frequently, a finding that is absolutely crucial for antibiotic treatment strategy.
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Affiliation(s)
- Pavla Kucova
- Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, 779 00 Olomouc, Czech Republic; (P.K.); (K.F.); (M.R.); (M.K.)
| | - Lumir Kantor
- Neonatal Department, University Hospital Olomouc, 779 00 Olomouc, Czech Republic;
| | - Katerina Fiserova
- Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, 779 00 Olomouc, Czech Republic; (P.K.); (K.F.); (M.R.); (M.K.)
| | - Jakub Lasak
- Neonatal Department, University Hospital Olomouc, 779 00 Olomouc, Czech Republic;
| | - Magdalena Röderova
- Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, 779 00 Olomouc, Czech Republic; (P.K.); (K.F.); (M.R.); (M.K.)
| | - Milan Kolar
- Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, 779 00 Olomouc, Czech Republic; (P.K.); (K.F.); (M.R.); (M.K.)
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Schmitt C, Novy M, Hascoët JM. Term newborns at risk for early-onset neonatal sepsis: Clinical surveillance versus systematic paraclinical test. Arch Pediatr 2021; 28:117-122. [PMID: 33446431 DOI: 10.1016/j.arcped.2020.11.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 10/06/2020] [Accepted: 11/21/2020] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Early-onset neonatal sepsis is a rare but potentially lethal infection that is very often suspected in daily practice. Previous national guidelines recommended the use of systematic paraclinical tests for healthy term newborns with suspected infection. These guidelines were updated in 2017 by the French Health Authority (Haute Autorité de santé), and promote initial clinical monitoring taking into account the infectious risk level for term and near-term born infants. OBJECTIVES To assess the impact of the new recommendations on antibiotic therapy prescription and invasive tests, and on the outcomes of infants born from 36weeks' gestation. MATERIALS AND METHODS This study compared the management and the outcome of neonates born from 36weeks' gestation at the level III University Hospital of Nancy, according to their infectious risk level during two periods, before and after the update of national recommendations: from July 1 to December 31, 2017, versus July 1 to December 31, 2018. Data were retrospectively collected from the infants' files. This study compared the number and length of antibiotic treatment and the number of invasive tests, the number of documented infections, the number and length of hospitalization, and mortality between the two periods. RESULTS During the first period, among 1248 eligible newborns, 643 presented an infectious risk factor, versus 1152 newborns with 343 having an infectious risk factor during the second period. Antibiotic treatment was initiated for 18 newborns during the first period (1.4%) and for nine during the second (0.8%) (P=0.13). The mean (SD) duration of the antibiotic treatment was longer in the first than in the second period: 6.3±2days vs. 3.1±2.3days (P=0.003). There was no death related to neonatal infection. A total of 1052 blood samples were collected during the first period versus 51 during the second (P<0.01). There was no documented infection. In the first period, there were 18 newborns (1.4%) hospitalized for suspected infection versus nine (0.8%) in the second period (P=0.13). The duration of hospitalization was 5.7±1.7days in the first period versus 5.2±3days in the second (P=0.33). CONCLUSION In this study, the application of the new guidelines enabled a reduction of antibiotic exposure and a reduction of invasive tests without additional risk.
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Affiliation(s)
- C Schmitt
- Neonatal Intensive Care Unit, Maternité Régionale, CHRU Nancy, 54000 Nancy, France.
| | - M Novy
- Neonatal Intensive Care Unit, Maternité Régionale, CHRU Nancy, 54000 Nancy, France
| | - J-M Hascoët
- Neonatal Intensive Care Unit, Maternité Régionale, CHRU Nancy, 54000 Nancy, France; DevAH, Lorraine University, 54000 Nancy, France
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Can immature platelet fraction be an early predictor for congenital pneumonia? Turk Arch Pediatr 2021; 55:409-417. [PMID: 33414659 PMCID: PMC7750339 DOI: 10.14744/turkpediatriars.2020.98965] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 04/02/2020] [Indexed: 11/20/2022]
Abstract
Aim: Timely diagnosis and treatment of congenital pneumonia are crucial. A new hematologic parameter, immature platelet fraction, has been used to gather clinical information on the prognosis of thrombocytopenia, as well as to measure inflammatory activity in adult patients. This study aimed to compare immature platelet fraction and sepsis biomarkers in late-preterm infants diagnosed as having congenital pneumonia and to evaluate its predictive value for congenital pneumonia. Material and Methods: Late-preterms were categorized based on infectious vs. non-infectious etiology of respiratory distress. Two sets of blood samples for markers were taken at 12–24 (sample-1) and 48–72 hours (sample-2) after birth. Immature platelet fraction was measured using a Sysmex XN-3000 analyzer. Results: From a total of 30 non-thrombocytopenic late-preterms, 16 were included in the congenital pneumonia group and 14 comprised the transient tachypnea group. The groups were comparable in terms of gestational age, birth weight, and cesarean section rate. The proportion of prolonged membrane rupture was significantly higher in the congenital pneumonia group. Values of immature platelet fraction-1, immature platelet fraction-2, and procalcitonin-2 were significantly higher in the congenital pneumonia group than in the transient tachypnea group. No significant differences were found between the groups in other biomarkers. It was determined that an immature platelet fraction-1 cut-off value of 2.9% could predict congenital pneumonia with a sensitivity of 65%, a specificity of 71.4%, a positive predictive value of 70.5%, and negative predictive value of 63.7% (area under the curve=0.724; p=0.028). Conclusion: Immature platelet fraction may have an early predictive role in the diagnosis of congenital pneumonia.
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Early-onset sepsis in term infants admitted to neonatal intensive care units (2011-2016). J Perinatol 2021; 41:157-163. [PMID: 33070153 PMCID: PMC7568457 DOI: 10.1038/s41372-020-00860-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 09/08/2020] [Accepted: 10/06/2020] [Indexed: 11/09/2022]
Abstract
OBJECTIVES Investigate characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. STUDY DESIGN Using a cohort design, we identified term infants evaluated for EOS with blood, cerebrospinal fluid, or urine cultures in 326 NICUs (2011-2016). Using multivariable logistic regression, we investigated the association between EOS and demographic characteristics. RESULTS Of 142,410 infants, 1197 (0.8%) had EOS, most commonly caused by group B Streptococcus (GBS; 40.6%). Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age <19 years, vasopressor treatment, and ventilator support. CONCLUSION(S) GBS was the most frequent cause of EOS. Early risk factor recognition may help daily management of term infants in NICUs.
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Aleem S, Wohlfarth M, Cotten CM, Greenberg RG. Infection control and other stewardship strategies in late onset sepsis, necrotizing enterocolitis, and localized infection in the neonatal intensive care unit. Semin Perinatol 2020; 44:151326. [PMID: 33158599 PMCID: PMC7550069 DOI: 10.1016/j.semperi.2020.151326] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Suspected or proven late onset sepsis, necrotizing enterocolitis, urinary tract infections, and ventilator associated pneumonia occurring after the first postnatal days contribute significantly to the total antibiotic exposures in neonatal intensive care units. The variability in definitions and diagnostic criteria in these conditions lead to unnecessary antibiotic use. The length of treatment and choice of antimicrobial agents for presumed and proven episodes also vary among centers due to a lack of supportive evidence and guidelines. Implementation of robust antibiotic stewardship programs can encourage compliance with appropriate dosages and narrow-spectrum regimens.
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Affiliation(s)
- Samia Aleem
- Department of Pediatrics, Duke University, Durham, NC, USA
| | | | | | - Rachel G. Greenberg
- Department of Pediatrics, Duke University, Durham, NC, USA,Duke Clinical Research Institute, Durham, NC, USA,Corresponding author at: Department of Pediatrics, Duke University, Durham, NC, USA
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韩 露, 徐 小, 童 笑, 张 欣, 刘 捷, 杨 立, 刘 慧, 闫 菊, 宋 志, 梅 亚, 米 荣, 秦 选, 刘 玉, 齐 宇, 张 巍, 曾 慧, 崔 红, 龙 卉, 郭 果, 陈 旭, 杨 召, 孙 芳, 付 晓, 王 长, 李 正. [Effect of breastfeeding on the development of infection-related diseases during hospitalization in late preterm infants in 25 hospitals in Beijing, China]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2020; 22:1245-1250. [PMID: 33327992 PMCID: PMC7735928 DOI: 10.7499/j.issn.1008-8830.2007065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 11/04/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVE To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, P=0.033). The multivariate logistic regression analysis showed that breastfeeding was an independent protective factor against infectious diseases (OR=0.534, P=0.004), while male sex, premature rupture of membranes, gestational diabetes mellitus, and asphyxia were risk factors for infectious diseases (OR=1.328, 5.386, 1.535, and 2.353 respectively, P < 0.05). CONCLUSIONS Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
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Affiliation(s)
- 露艳 韩
- 清华大学第一附属医院儿科, 北京 100016Department of Pediatrics, First Hospital of Tsinghua University, Beijing 100016, China
| | - 小静 徐
- 清华大学第一附属医院儿科, 北京 100016Department of Pediatrics, First Hospital of Tsinghua University, Beijing 100016, China
| | | | | | | | | | | | | | | | - 亚波 梅
- 中国人民解放军总医院第七医学中心儿科, 北京 100710
| | - 荣 米
- 首都儿科研究所附属儿童医院儿科, 北京 100191
| | - 选光 秦
- 首都医科大学附属北京朝阳医院儿科, 北京 100043
| | - 玉环 刘
- 首都医科大学附属北京地坛医院儿科, 北京 100015
| | - 宇洁 齐
- 首都医科大学附属北京儿童医院儿科, 北京 100045
| | - 巍 张
- 首都医科大学附属北京妇产医院儿科, 北京 100026
| | - 慧慧 曾
- 首都医科大学附属北京妇产医院儿科, 北京 100026
| | - 红 崔
- 首都医科大学附属北京友谊医院儿科, 北京 100050
| | - 卉 龙
- . 中国人民解放军总医院第一医学中心儿科, 北京 100853
| | - 果 郭
- 中国人民解放军总医院第五医学中心, 北京 100039
| | - 旭琳 陈
- 中国人民解放军总医院第三医学中心, 北京 100101
| | - 召意 杨
- 中国人民解放军总医院第六医学中心儿科, 北京 100048
| | | | | | - 长燕 王
- 中国医学科学院北京协和医学院北京协和医院儿科, 北京 100730
| | - 正红 李
- 中国医学科学院北京协和医学院北京协和医院儿科, 北京 100730
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Kajimoto E, Endo M, Fujimoto M, Matsuzaki S, Fujii M, Yagi K, Kakigano A, Mimura K, Tomimatsu T, Serada S, Takeuchi M, Yoshino K, Ueda Y, Kimura T, Naka T. Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection. PLoS One 2020; 15:e0242076. [PMID: 33211747 PMCID: PMC7676652 DOI: 10.1371/journal.pone.0242076] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 10/27/2020] [Indexed: 11/21/2022] Open
Abstract
This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group, n = 14) and CAM without fetal infection (CAM-f[−] group, n = 31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all, p > 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21–13.7] μg/ml) than in the CAM-f(−) (3.61 [2.71–4.65] μg/ml) or control group (3.39 [2.81–3.93] μg/ml; p < 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 μg/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera and LRG mRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p < 0.01). In vitro experiments using a fetal liver-derived cell line (WRL68) showed that the expression of LRG mRNA was significantly increased after interleukin (IL)-6, IL-1β, and tumor necrosis factor- alpha (TNF-α) stimulation (p < 0.01); the induction was considerably stronger following IL-6 and TNF-α stimulation (p < 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG production in utero.
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Affiliation(s)
- Etsuko Kajimoto
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Obstetrics and Gynecology, Japan Community Health Care Organization Osaka Hospital, Osaka, Japan
| | - Masayuki Endo
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Children and Women’s Health, Osaka University Graduate School of Medicine, Osaka, Japan
- Division of Health Science, Graduate School of medicine, StemRIM Institute of Regeneration-Inducting Medicine, Osaka University, Osaka, Japan
| | - Minoru Fujimoto
- Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi, Japan
- * E-mail:
| | - Shinya Matsuzaki
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Makoto Fujii
- Division of Health Science, Graduate School of medicine, StemRIM Institute of Regeneration-Inducting Medicine, Osaka University, Osaka, Japan
| | - Kazunobu Yagi
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Aiko Kakigano
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazuya Mimura
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takuji Tomimatsu
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Satoshi Serada
- Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi, Japan
| | - Makoto Takeuchi
- Department of Pathology, Osaka Women’s and Children’s Hospital, Osaka, Japan
| | - Kiyoshi Yoshino
- Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yutaka Ueda
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tadashi Kimura
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tetsuji Naka
- Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi, Japan
- Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
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Sgro M, Campbell DM, Mellor KL, Hollamby K, Bodani J, Shah PS. Early-onset neonatal sepsis: Organism patterns between 2009 and 2014. Paediatr Child Health 2020; 25:425-431. [PMID: 33173553 PMCID: PMC7606168 DOI: 10.1093/pch/pxz073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 04/08/2019] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE To evaluate trends in organisms causing early-onset neonatal sepsis (EONS). Congruent with recent reports, we hypothesized there would be an increase in EONS caused by Escherichia coli. STUDY DESIGN National data on infants admitted to neonatal intensive care units from 2009 to 2014 were compared to previously reported data from 2003 to 2008. We report 430 cases of EONS from 2009 to 2014. Bivariate analyses were used to analyze the distribution of causative organisms over time and differences by gestational age. Linear regression was used to estimate trends in causative organisms. RESULTS Since 2003, there has been a trend of increasing numbers of cases caused by E coli (P<0.01). The predominant organism was E coli in preterm infants and Group B Streptococcus in term infants. CONCLUSIONS With the majority of EONS cases now caused by E coli, our findings emphasize the importance of continued surveillance of causative organism patterns and developing approaches to reduce cases caused by E coli.
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Affiliation(s)
- Michael Sgro
- Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario
- Department of Pediatrics, St. Michael’s Hospital, Toronto, Ontario
- Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario
| | - Douglas M Campbell
- Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario
- Department of Pediatrics, St. Michael’s Hospital, Toronto, Ontario
- Division of Neonatology, Department of Pediatrics, University of Toronto, Toronto, Ontario
| | | | | | - Jaya Bodani
- Department of Pediatrics, Regina Qu’Appelle Health Region, Regina, Saskatchewan
| | - Prakesh S Shah
- Division of Neonatology, Department of Pediatrics, University of Toronto, Toronto, Ontario
- Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario
- Maternal-Infant Care Research Center, Mount Sinai Hospital, Toronto, Ontario
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Martines RB, Ritter JM, Gary J, Shieh WJ, Ordi J, Hale M, Carrilho C, Ismail M, Traore CB, Ndibile BE, Sava S, Arjuman F, Kamal M, Rahman MM, Blau DM, Zaki SR. Pathology and Telepathology Methods in the Child Health and Mortality Prevention Surveillance Network. Clin Infect Dis 2020; 69:S322-S332. [PMID: 31598668 DOI: 10.1093/cid/ciz579] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
This manuscript describes the Child Health and Mortality Prevention Surveillance (CHAMPS) network approach to pathologic evaluation of minimally invasive tissue sampling (MITS) specimens, including guidelines for histopathologic examination and further diagnostics with special stains, immunohistochemistry, and molecular testing, as performed at the CHAMPS Central Pathology Laboratory (CPL) at the Centers for Disease Control and Prevention, as well as techniques for virtual discussion of these cases (telepathology) with CHAMPS surveillance locations. Based on review of MITS from the early phase of CHAMPS, the CPL has developed standardized histopathology-based algorithms for achieving diagnoses from MITS and telepathology procedures in conjunction with the CHAMPS sites, with the use of whole slide scanners and digital image archives, for maximizing concurrence and knowledge sharing between site and CPL pathologists. These algorithms and procedures, along with lessons learned from initial implementation of these approaches, guide pathologists at the CPL and CHAMPS sites through standardized diagnostics of MITS cases, and allow for productive, real-time case discussions and consultations.
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Affiliation(s)
- Roosecelis B Martines
- Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jana M Ritter
- Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Joy Gary
- Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Wun-Ju Shieh
- Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jaume Ordi
- ISGlobal, Hospital Clínic, Universitat de Barcelona, Spain
| | - Martin Hale
- Division of Anatomical Pathology, University of the Witswatersrand, Johannesburg, South Africa
| | - Carla Carrilho
- Department of Pathology, Faculty of Medicine, Eduardo Mondlane University and Maputo Central Hospital, Mozambique
| | - Mamudo Ismail
- Department of Pathology, Faculty of Medicine, Eduardo Mondlane University and Maputo Central Hospital, Mozambique
| | - Cheick Boudadari Traore
- Department of Pathological Anatomy and Cytology, University Hospital of Point G, Bamako, Mali
| | | | - Solomon Sava
- Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu County, Kenya
| | - Farida Arjuman
- National Institute of Cancer Research and Hospital, Dhaka, Bangladesh
| | - Mohammed Kamal
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | - Dianna M Blau
- Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sherif R Zaki
- Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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