Barbara J Stoll1, Karen M Puopolo2, Nellie I Hansen3, Pablo J Sánchez4, Edward F Bell5, Waldemar A Carlo6, C Michael Cotten7, Carl T D'Angio8, S Nadya J Kazzi9, Brenda B Poindexter10,11, Krisa P Van Meurs12, Ellen C Hale13, Monica V Collins6, Abhik Das14, Carol J Baker1, Myra H Wyckoff15, Bradley A Yoder16, Kristi L Watterberg17, Michele C Walsh18, Uday Devaskar19, Abbot R Laptook20, Gregory M Sokol21, Stephanie J Schrag22, Rosemary D Higgins23,24. 1. Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center, Houston and Children's Memorial Hermann Hospital, Houston. 2. Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia. 3. Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina. 4. Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus. 5. Department of Pediatrics, University of Iowa, Iowa City. 6. Division of Neonatology, University of Alabama at Birmingham. 7. Department of Pediatrics, Duke University, Durham, North Carolina. 8. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York. 9. Department of Pediatrics, Wayne State University, Detroit, Michigan. 10. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. 11. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. 12. Division of Neonatal and Developmental Medicine, Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, California. 13. Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia. 14. Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland. 15. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas. 16. Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City. 17. Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque. 18. Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio. 19. Department of Pediatrics, UCLA (University of California, Los Angeles). 20. Department of Pediatrics, Women & Infants Hospital, Brown University, Providence, Rhode Island. 21. Department of Pediatrics, Indiana University School of Medicine, Indianapolis. 22. Centers for Disease Control and Prevention, Atlanta, Georgia. 23. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland. 24. Office of Research, George Mason University College of Health and Human Services, Fairfax, Virginia.
Abstract
Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.
Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.
Authors: Barbara J Stoll; Nellie I Hansen; Rosemary D Higgins; Avroy A Fanaroff; Shahnaz Duara; Ronald Goldberg; Abbot Laptook; Michelle Walsh; William Oh; Ellen Hale Journal: Pediatr Infect Dis J Date: 2005-07 Impact factor: 2.129
Authors: Jonathan M Wortham; Nellie I Hansen; Stephanie J Schrag; Ellen Hale; Krisa Van Meurs; Pablo J Sánchez; Joseph B Cantey; Roger Faix; Brenda Poindexter; Ronald Goldberg; Matthew Bizzarro; Ivan Frantz; Abhik Das; William E Benitz; Andi L Shane; Rosemary Higgins; Barbara J Stoll Journal: Pediatrics Date: 2015-12-30 Impact factor: 7.124
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Authors: Thomas H Dierikx; Anton H L C van Kaam; Tim G J de Meij; Ralph de Vries; Wes Onland; Douwe H Visser Journal: Pediatr Res Date: 2021-10-28 Impact factor: 3.953
Authors: Karen M Puopolo; Sagori Mukhopadhyay; Nellie I Hansen; Dustin D Flannery; Rachel G Greenberg; Pablo J Sanchez; Edward F Bell; Sara B DeMauro; Myra H Wyckoff; Eric C Eichenwald; Barbara J Stoll Journal: Clin Infect Dis Date: 2022-10-12 Impact factor: 20.999