Early-Onset Sepsis an NICHD/CDC Surveillance Study (EOSII)

This prospective surveillance study will be conducted over a 2 year period to determine current rates of Early-Onset Sepsis (EOS)/ Early-Onset Meningitis (EOM), associated pathogens, antimicrobial resistance, signs and symptoms and infant outcomes.

Study Overview

• Status: Completed
• Conditions: Infant, Newborn, Diseases; Early Onset Neonatal Sepsis; Early-Onset Meningitis

Detailed Description

Neonatal pathogens other than group B Streptococcus (GBS) and resistant to beta-lactam antibiotics have emerged as the most common etiologic agents of EOS and EOM among preterm and term neonates and result in high mortality rates, potentially offsetting the decreased burden of early-onset GBS disease prevented by maternal intrapartum chemoprophylaxis.

Primary Outcomes of this study:

1. To determine current hospital-based rates of early-onset neonatal infection (total, GA-specific and BW-specific, and pathogen-specific) in term and preterm infants in the era of maternal intrapartum antibiotic prophylaxis to prevent vertical transmission of group B streptococcal disease. Early-onset infection comprises EOS and/or EOM and is defined as isolation of a pathogen from blood or cerebrospinal fluid (CSF) obtained within 72 hours of birth and provision of appropriate antibiotic treatment for 5 or more days (or <5 days if death occurs while receiving antibiotic therapy).
2. To determine the antimicrobial susceptibility patterns of organisms associated with EOS and EOM

The case control aspect of this study will address 2 major conundrums regarding EOS: Can we identify risk factors for early-onset Gram-negative infections that might lead to intervention strategies to reduce risk and can we identify infants born to mothers with clinical chorioamnionitis who are at highest risk for early-onset sepsis and thus warrant antibiotic treatment soon after birth?

• Study Type: Observational
• Enrollment (Actual): 570

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90025
      • University of California - Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Cincinnati Children's Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43205
      • Research Institute at Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Brown University, Women & Infants Hospital of Rhode Island
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will include all live born infants who are at least 22 weeks GA and have a birth weight >400 grams and are delivered at NRN centers.

Description

Inclusion Criteria:

• Case Surveillance: Live born infants with gestational age of at least 22 weeks and birth weight >400 g and <72 hours of age who are delivered at NRN hospitals and have early-onset sepsis and meningitis defined as isolation of a pathogen from blood or CSF obtained within 72 hours of birth and provision of appropriate antibiotic treatment for 5 or more days (or <5 days if death occurs while receiving antibiotic therapy).
• Controls: Live born infants with gestational age of at least 22 weeks and birth weight >400 g who are delivered at NRN hospitals and have not been evaluated for early-onset sepsis (<72 hours of age) or if evaluated, they have sterile blood and/or CSF cultures and were not treated with prolonged antibiotics for clinical "culture negative" sepsis. Controls for infants with Gram-negative infection will be infants without early-onset infection. Controls for infants born to mothers with clinical chorioamnionitis will be infants without early-onset infection born to mothers with clinical chorioamnionitis. Control infants will be born at the same hospital as cases, with the same gestational age grouping as cases (22 0/7 - 28 6/7 weeks; 29 0/7 - 33 6/7 weeks; 34 0/7 - 36 6/7 weeks; and ≥ 37 weeks).

Exclusion Criteria:

• Stillbirths and infants who die in the delivery room will be excluded.
• Infants who die within 12 hours of age will be excluded if they have not been evaluated for possible infection-ie, do not have a blood culture obtained to identify EOS.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
EOS infant / mother with chorio; Infant with EOS (Gram-positive or Gram-negative) and mother with Chorioamnionitis
EOS infant / mother without chorio; Infant with EOS (Gram-positive or Gram-negative) and mother without Chorioamnionitis
EOS Gram-neg infant / mother with chorio; Infant with Gram-negative EOS and mother with Chorioamnionitis
Gram-neg infant / mother without chorio; Infant with Gram-negative EOS and mother without Chorioamnionitis
Gram-pos infant / mother with chorio; Infant with Gram-positive EOS and mother with Chorioamnionitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine current hospital-based rates of early-onset neonatal infection	First 72 hours
To determine the antimicrobial susceptibility patterns of organisms associated with EOS and EOM	First 72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
To identify risk factors associated with EOS/EOM due to Gram-negative pathogens (case control comparison)	First 72 hours
To determine the clinical signs/symptoms and laboratory abnormalities associated with EOS/EOM	First 72 hours
To identify risk factors for EOS/EOM in infants born to mothers with chorioamnionitis (case control comparison)	First 72 hours
To determine if term infants with EOS, identified because of maternal chorioamnionitis, can be asymptomatic at birth	First 72 hours
To determine sepsis-associated mortality rates (total, GA-specific and BW-specific, pathogen-specific) for infants with EOS/EOM	First 72 hours
To review changes over time in overall rates of EOS and EOM, pathogens associated with infection, risk factors for infection, clinical and laboratory abnormalities, and sepsis-associated mortality	9-11 years

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Brenda Poindexter, MD, Children's Hospital Medical Center, Cincinnati; Principal Investigator: Carl D'Angio, MD, University of Rochester; Study Director: Barbara Stoll, MD, The University of Texas Health Science Center, Houston; Principal Investigator: Michele Walsh, MD, Case Western Reserve University, Rainbow Babies and Children's Hospita; Principal Investigator: Abbot Laptook, MD, Brown University, Women & Infants Hospital of Rhode Island; Principal Investigator: Kathleen Kennedy, MD, MPH, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: April 2, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 7, 2015

Study Record Updates

• Last Update Posted (Actual): March 11, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Meningitis; Infant, Newborn, Diseases; Neonatal Sepsis
• Other Study ID Numbers: NICHD-NRN-0055; UG1HD034216 (U.S. NIH Grant/Contract); UG1HD027904 (U.S. NIH Grant/Contract); UG1HD021364 (U.S. NIH Grant/Contract); UG1HD027853 (U.S. NIH Grant/Contract); UG1HD040689 (U.S. NIH Grant/Contract); UG1HD040492 (U.S. NIH Grant/Contract); UG1HD027851 (U.S. NIH Grant/Contract); UG1HD087229 (U.S. NIH Grant/Contract); UG1HD053109 (U.S. NIH Grant/Contract); UG1HD068278 (U.S. NIH Grant/Contract); UG1HD068244 (U.S. NIH Grant/Contract); UG1HD068263 (U.S. NIH Grant/Contract); UG1HD027880 (U.S. NIH Grant/Contract); UG1HD053089 (U.S. NIH Grant/Contract); UG1HD087226 (U.S. NIH Grant/Contract); U10HD036790 (U.S. NIH Grant/Contract); UG1HD027856 (U.S. NIH Grant/Contract); UG1HD068284 (U.S. NIH Grant/Contract); UG1HD068270 (U.S. NIH Grant/Contract)