Neonatal Sepsis

1. Epidemiology
   1. Incidence: 1 to 8 cases per 1000 live births
   2. Meningitis occurs in one third of Sepsis cases
2. Risk Factors
   1. Major
      1. Maternal prolonged Rupture of Membranes >24 hours
      2. Intrapartum maternal fever >38 C (>100.4 F)
      3. Chorioamnionitis
      4. Sustained Fetal Tachycardia >160 beats per minute
   2. Minor
      1. Intrapartum maternal fever >37.5 C (>99.5 F)
      2. Twin Gestation
      3. Premature infant (<37 weeks)
      4. Maternal Leukocytosis (White Blood Cell count >15000)
      5. Rupture of Membranes > 12 hours
      6. Tachypnea (<1 hour)
      7. Maternal Group B Streptococcus Colonization
      8. Low APGAR (<5 at 1 minute)
      9. Low birth weight (<1500 grams)
      10. Foul lochia
3. Etiologies
   1. Most common
      1. Group B Beta-hemolytic Streptococcus (Group B Strep)
      2. Escherichia coli K1 (ECK1)
      3. Listeria monocytogenes
         1. Rare in the United States
         2. Predominant in Spain
   2. Other pathogens
      1. HaemophilusInfluenzae
      2. Coagulase-negative staphylococci (Nosocomial)
4. Signs
   1. Respiratory distress (90%)
      1. Tachypnea
      2. Apnea
      3. Hypoxia
      4. Flaring or grunting
      5. Irregular respirations
   2. Temperature instability sustained over 1 hour (30%)
      1. Newborn Temperature < 97 F (36 C)
      2. Newborn Temperature > 99.6 F (37 C)
   3. Gastrointestinal symptoms
      1. Vomiting
      2. Diarrhea
      3. Abdominal distention
      4. Ileus
      5. Poor feeding
      6. Splenomegaly
   4. Neurologic
      1. Activity decreased or lethargy
      2. Irritability
      3. Tremor or Seizure
      4. Hyporeflexia or hypotonia
      5. High pitched cry
      6. Swelling of Fontanel
   5. Cardiovascular
      1. Hypotension
      2. Metabolic Acidosis
      3. Tachycardia
   6. Skin
      1. Pallor or skin mottling
      2. Petechiae or Purpura
      3. Cold or clammy skin
      4. Cyanosis
      5. Jaundice
5. Labs
   1. Complete Blood Count (findings suggestive of Sepsis)
      1. White Blood Cell Count
         1. Decreased below 5000 /mm3
         2. Increased above 25000 /mm3
      2. Absolute Neutrophil Count (ANC) < 1000 /mm3
      3. Bands to total Neutrophil Count ratio > 0.2
      4. Immature to mature Neutrophil Count ratio > 0.2
   2. Blood Culture (positive in 5-10% of Neonatal Sepsis)
   3. Arterial Blood Gas
      1. Indicated for signs or symptoms of Hypoxia
   4. Lumbar Puncture
      1. Indications
         1. Sepsis is considered primary diagnosis
         2. Blood Culture positive
         3. Neurologic signs or symptoms
      2. Specific Tests
         1. CSF Examination
         2. CSF Culture
         3. CSF Antigens
   5. Urinalysis and Urine Culture
      1. Indicated for late-onset Neonatal Sepsis
      2. Not useful in perinatal period (age <3 days old)
   6. Consider Urine antigens
      1. Escherichia coli
      2. NeisseriaMeningitis
      3. Streptococcal Pneumoniae
      4. Group B Streptococcus
6. Radiology
   1. Chest XRay
7. Management: General
   1. Monitor infant for signs of Sepsis
   2. Antibiotic indications (contrast with observation only)
      1. Symptomatic infants
      2. Asymptomatic infants with >2 risk factors (see above)
   3. Continue monitoring and antibiotics for 48 to 72 hours
      1. Indications to continue antibiotics 14 to 21 days
         1. Symptomatic newborn
         2. Blood Culture positive
      2. Discontinue antibiotics and monitoring if
         1. Blood Cultures negative at 48 to 72 hours and
         2. No signs of Sepsis on examination
   4. Signs of Sepsis with negative culture
      1. Consider Neonatal HSV infection
8. Management: Antibiotics for Early Onset (age <1 week)
   1. Bacterial spectrum
      1. Group B Streptococcus
      2. Escherichia coli
      3. Klebsiella
      4. Enterobacter
      5. Staphylococcus aureus (not common)
      6. Listeria (rare in United States)
   2. Primary Antibiotic Protocol
      1. Ampicillin (Meningitis dose often used empirically)
         1. Sepsis: 50 mg/kg/dose IV or IM q12 hours
         2. Meningitis: 100 mg/kg/dose IV or IM q12 hours
      2. Gentamicin
         1. Gestation <28 weeks: 2.5 mg/kg/dose IV/IM q24 hours
         2. Gestation <34 weeks: 2.5 mg/kg/dose IV/IM q18 hours
         3. Gestation >34 weeks: 2.5 mg/kg/dose IV/IM q12 hours
   3. Alternative Options
      1. Alternative Protocol 1
         1. Ampicillin (dosed as above)
         2. Cefotaxime 50 mg/kg/dose IV or IM q12 hours
      2. Alternative Protocol 2
         1. Ampicillin (dosed as above)
         2. Ceftriaxone 50 mg/kg IV or IM q24 hours
9. Management: Antibiotics for Late Onset (age 1-4 weeks)
   1. Coverage broadened over early onset Sepsis
      1. HaemophilusInfluenzae
      2. Staphylococcus epidermidis
   2. Antibiotic Dosing for infant over 7 days old
      1. Ampicillin (the higher dose in possible Meningitis)
         1. Weight <2 kg: 25-50 mg/kg/dose IV or IM q8 hours
         2. Weight >2 kg: 25-50 mg/kg/dose IV or IM q6 hours
      2. Gentamicin
         1. Gestation <37 weeks: 2.5 mg/kg/dose IV/IM q12 hours
         2. Gestation >37 weeks: 2.5 mg/kg/dose IV/IM q8 hours
   3. Primary Protocol 1
      1. Ampicillin (dosed as above)
      2. Cefotaxime 50 mg/kg/dose IV or IM q8 hours
   4. Primary Protocol 2
      1. Ampicillin (dosed as above)
      2. Ceftriaxone 75 mg/kg/dose IV or IM q24 hours
   5. Alternative Protocol
      1. Ampicillin (dosed as above)
      2. Gentamicin (dosed as above)
10. Prevention
    1. Prolonged Rupture of MembranesGBS Prophylaxis
    2. Routine Group B Strep Screening in pregnancy (36 weeks)
11. References
    1. Behrman (2000) Nelson Pediatrics, Saunders, p. 550
    2. Cloherty (1991) Neonatal Care, Little Brown, P. 146-58
    3. Gilbert (2001) Sanford Guide, ATI, p. 42