Early-onset Neonatal Sepsis

Background

• Early-onset neonatal sepsis is a suspected or proven systemic infection occurring within the first 72 hours of life, although some experts expand the definition to include systemic infections occurring in infants up to age 7 days.
• Neonates with early-onset sepsis usually become infected via vertical transmission in utero or during delivery. The immature neonatal immune system may have a limited ability to fight infection.
• The most common pathogens are group B Streptococcus (GBS) and Escherichia coli. Less common causes include other gram-negative enteric bacilli, Staphylococcus aureus, Haemophilus influenzae, and Listeria monocytogenes.
• Important risk factors for early-onset neonatal sepsis include:
  • prematurity
  • confirmed or suspected chorioamnionitis or intra-amniotic infection during labor or in the 24 hours before or after delivery
  • suspected or confirmed infection in a co-born sibling from a multiple pregnancy
  • maternal GBS colonization, bacteriuria, or infection in current pregnancy, or maternal history of GBS infection in a previous neonate
  • intrapartum fever ≥ 38 degrees C (100.4 degrees F)
  • prolonged rupture of membranes for > 18 hours
• Neonatal sepsis may present with clinical signs of infection, for example:
  • apnea or respiratory distress
  • tachycardia, bradycardia, hypotension, or shock
  • altered behavior, responsiveness, or muscle tone
  • seizure
  • fever or hypothermia
  • feeding problems
  • jaundice
  • oliguria > 24 hours
• Neonatal infections can also be asymptomatic, and may be detected on the testing of infants with risk factors for infection.

Evaluation

• Suspect early-onset sepsis in neonates with clinical signs of infection and/or risk factors for infection.
• Assessment of the risk of early-onset sepsis according to gestational age, risk factors, and clinical observation will direct laboratory evaluation and management decisions.
• If it is indicated by the risk assessment, initial testing should include blood culture and complete blood count with differential.
• Perform a lumbar puncture if the clinical exam suggests meningitis, the blood culture is positive, or other test results or clinical course strongly suggest infection.
• Consider a chest x-ray in infants with respiratory signs and consider additional specimens for microscopy and culture in infants with symptoms of focal infection.
• Isolation of a pathogenic microorganism from blood or cerebrospinal fluid confirms the diagnosis.

Management

• Begin resuscitation (including respiratory and hemodynamic support) in infants with suspected septic shock (Strong recommendation).
• Start empiric antibiotic therapy (after obtaining cultures if possible) if it is indicated based on the assessment of the risk of early-onset sepsis. Do not wait for the results of diagnostic laboratory evaluations.
• Three methods of risk assessment in term infants include categorical risk assessment, multivariate risk assessment, and enhanced clinical observation.
• For premature neonates (gestational age ≤ 34 weeks), management is guided by risk of early-onset sepsis based on the circumstances of birth.
• If starting antibiotic therapy, initiate treatment with antibiotics directed toward likely pathogens, and if the infection is confirmed, adjust the regimen based on the organism identified and susceptibilities.
  • In the United States, the preferred empiric regimen for most infants is IV ampicillin plus IV gentamicin.
  • For empiric treatment of meningitis:
    • Infectious Diseases Society of America (IDSA) recommends IV ampicillin plus either IV cefotaxime or an IV aminoglycoside (Strong recommendation).
    • National Institute for Health and Care Excellence (NICE) recommends IV cefotaxime plus IV amoxicillin (IV amoxicillin not used in the United States).
  • Antibiotic dosing is based on factors, such as, gestational age, weight, and clinical condition; if treating with gentamicin, consider therapeutic drug monitoring to guide the dosing.
• If early-onset sepsis is confirmed, determine the duration of antibiotic therapy based on the pathogen and the site of infection, but continue antibiotics at least until cultures are negative and the neonate has recovered clinically.
• Consider discontinuing empiric antibiotics if blood cultures remain sterile at 36-48 hours of incubation.
• In infants with refractory septic shock, suspect an underlying noninfectious disorder and provide condition-specific treatment as indicated (Strong recommendation).