Early-Onset Sepsis an NICHD/CDC Surveillance Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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: 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). 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?

Official Title
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Early-Onset Sepsis an NICHD/CDC Surveillance Study

Conditions
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Infant, Newborn, Diseases, Early Onset Neonatal Sepsis, Early-Onset Meningitis

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 72 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| EOS infant / mother with chorio<br>Infant with EOS (Gram-positive or Gram-negative) and mother with Chorioamnionitis | |
| EOS infant / mother without chorio<br>Infant with EOS (Gram-positive or Gram-negative) and mother without Chorioamnionitis | |
| EOS Gram-neg infant / mother with chorio<br>Infant with Gram-negative EOS and mother with Chorioamnionitis | |
| Gram-neg infant / mother without chorio<br>Infant with Gram-negative EOS and mother without Chorioamnionitis | |
| Gram-pos infant / mother with chorio<br>Infant with Gram-positive EOS and mother with Chorioamnionitis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |