Late-onset Neonatal Sepsis

Background

• Late-onset neonatal sepsis is a suspected or proven systemic infection occurring after the first 72 hours of life in an infant ≤ 28 days old, although some experts expand the definition to include infections occurring after the first 4-7 days of life.
• Neonates with late-onset sepsis usually become infected after birth, when exposed to environmental pathogens that the immature neonatal immune system may have limited ability to fight.
  • Infection is often acquired through contact with hospital staff, family members, or contaminated equipment.
  • Central line-associated bloodstream infection is a common etiology of late-onset sepsis among infants in the neonatal intensive care unit.
• Late-onset sepsis is usually caused by bacterial pathogens, but can also be due to fungi and viruses.
  • The most common pathogens are gram-positive bacteria, especially coagulase-negative staphylococci, Staphylococcus aureus, and enterococci.
  • The most common gram-negative pathogens are Escherichia coli, Klebsiella species, and Enterobacter species.
• Risk factors for late-onset sepsis include preterm birth, low birth weight, interventions such as vascular catheterization, mechanical ventilation, or hyperalimentation, and prolonged hospital stay.
• Late-onset neonatal sepsis usually presents with clinical signs of infection, for example:
  • temperature instability (hypothermia or fever), poor or high-pitched cry, feeding difficulties, lethargy, altered muscle tone, tachycardia or bradycardia, respiratory distress, apnea, or seizure
  • localized signs of infection such as skin lesions or periumbilical erythema
  • signs of shock such as hypotension, and abnormal pulses or capillary refill

Evaluation

• Suspect late-onset sepsis in neonates with clinical signs of infection, especially in infants with risk factors for infection.
• Initial testing should include a complete blood count with differential, blood culture, and lumbar puncture.
• Also consider:
  • biomarkers of infection such as C-reactive protein (CRP) and procalcitonin (PCT)
  • polymerase chain reaction (PCR)
  • urine culture
  • chest x-ray in infants with respiratory signs
  • additional specimens for microscopy and culture, such as tracheal aspirate (if intubated) or swab of skin lesion
  • heart rate characteristics monitoring
• Isolation of a pathogenic microorganism from blood, cerebrospinal fluid, urine, respiratory secretions, or other normally sterile site confirms the diagnosis.
• If possible, obtain cultures before starting antibiotics, but do not delay antimicrobial therapy to collect specimens or await test results in ill-appearing neonates.

Management

• Begin resuscitation (including respiratory and hemodynamic support) in infants with suspected septic shock (Strong recommendation).
• Start parenteral empiric antibiotics promptly in neonates with suspected or proven sepsis (after obtaining cultures if possible).
  • Initiate treatment with antibiotics directed toward likely pathogens, and if infection is confirmed, adjust the regimen based on the organism identified and susceptibilities.
  • For empiric treatment of meningitis, start IV ampicillin plus either IV cefotaxime or an IV aminoglycoside (Strong recommendation).
  • In neonates without meningitis, consider as first-line options:
    • for community-acquired sepsis or pneumonia - gentamicin plus either ampicillin or penicillin
    • for hospital-acquired sepsis - either ampicillin or penicillin, in combination with either gentamicin or amikacin
    • for suspected staphylococcal infection - aminoglycoside plus either vancomycin or a penicillinase-resistant penicillin
  • Antibiotic dosing is based on factors such as gestational and chronologic age, weight, and clinical condition; if treating with an aminoglycoside, consider therapeutic drug monitoring to guide dosing.
• Consider discontinuing empiric antibiotic therapy after 48 hours if cultures are negative and the neonate is clinically stable.
• If late-onset sepsis is confirmed, determine the duration of antibiotic therapy based on the pathogen and site of infection, but continue antibiotics at least until cultures are negative and the neonate has recovered clinically.
• In infants with refractory septic shock, suspect an underlying noninfectious disorder and provide condition-specific treatment as indicated (Strong recommendation). If no underlying disorder is identified, consider extracorporeal membrane oxygenation (ECMO) (Strong recommendation).