How to diagnose sepsis in neonates?

Diagnosing Sepsis in Neonates

Septic shock should be suspected in any newborn with tachycardia, respiratory distress, poor feeding, poor tone, poor color, tachypnea, diarrhea, or reduced perfusion, particularly in the presence of a maternal history of chorioamnionitis or prolonged rupture of membranes. 1

Clinical Presentation

• Neonatal sepsis often presents with nonspecific signs that require careful assessment:

  • Tachycardia 1
  • Respiratory distress or tachypnea 1
  • Poor feeding 1
  • Poor tone 1
  • Poor color or mottling 1
  • Reduced perfusion 1
  • Diarrhea 1
  • Change in mental status (irritability, lethargy) 1
  • Prolonged capillary refill >2 seconds 1
  • Diminished pulses (cold shock) or bounding pulses (warm shock) 1
  • Decreased urine output <1 ml/kg/h 1

• Maternal risk factors that increase suspicion:

  • Chorioamnionitis 1
  • Prolonged rupture of membranes (≥18 hours) 1
  • GBS colonization without adequate intrapartum antibiotic prophylaxis 1

Differential Diagnosis

• Important to distinguish septic shock from:
  • Cardiogenic shock due to ductal-dependent congenital heart disease (look for hepatomegaly, cyanosis, cardiac murmur, differential blood pressures/pulses) 1
  • Inborn errors of metabolism (check for hyperammonemia, hypoglycemia) 1
  • Persistent pulmonary hypertension of the newborn (PPHN) 1

Diagnostic Approach

Initial Assessment

• Perform thorough clinical assessment for signs of sepsis listed above 1
• Evaluate for therapeutic endpoints:
  • Capillary refill ≤2 seconds 1
  • Normal pulses without differential between peripheral and central 1
  • Warm extremities 1
  • Urine output >1 mL/kg/h 1
  • Normal mental status 1
  • Normal blood pressure for age 1
  • Normal glucose and calcium concentrations 1

Laboratory Evaluation

For neonates with signs of sepsis:

• Obtain full diagnostic evaluation: 1
  • Blood culture (gold standard for definitive diagnosis) 2
  • Complete blood count with white blood cell differential and platelet count 1
  • Chest radiograph (if respiratory symptoms present) 1
  • Lumbar puncture if stable enough and sepsis is suspected (15-38% of infants with meningitis have sterile blood cultures) 1

For well-appearing infants with maternal risk factors:

• If mother received inadequate GBS prophylaxis and infant is <37 weeks OR rupture of membranes ≥18 hours: 1
  • Limited evaluation: blood culture and CBC with differential and platelets 1
  • Observation for ≥48 hours 1

Monitoring

• Temperature 1
• Preductal and postductal pulse oximetry 1
• Intra-arterial (umbilical or peripheral) blood pressure 1
• Continuous electrocardiogram 1
• Arterial pH 1
• Urine output 1
• Glucose and ionized calcium concentration 1

Specific Clinical Scenarios

Scenario 1: Symptomatic Neonate with Signs of Sepsis

• Perform full diagnostic evaluation (blood culture, CBC with differential, chest X-ray if respiratory symptoms, lumbar puncture if stable) 1
• Start empirical antimicrobial therapy immediately (typically intravenous ampicillin and gentamicin) 1
• Monitor therapeutic endpoints and adjust treatment accordingly 1
• Discontinue antibiotics if clinical course and laboratory evaluation exclude sepsis 1

Scenario 2: Well-appearing Infant with Maternal Chorioamnionitis

• Perform limited evaluation (blood culture, CBC with differential) 1
• Start empirical antimicrobial therapy 1
• Monitor for ≥48 hours 1
• Discontinue antibiotics if cultures remain negative and infant remains well 1

Scenario 3: Well-appearing Term Infant with Inadequate Maternal GBS Prophylaxis

• If ≥37 weeks AND membrane rupture <18 hours: observe for ≥48 hours without routine testing 1
• If <37 weeks OR membrane rupture ≥18 hours: limited evaluation and observation for ≥48 hours 1

Emerging Diagnostic Tools

• Serum (1,3)-Beta-D-glucan (BDG) shows promise for diagnosing invasive fungal infections:

  • At 80 pg/mL threshold: sensitivity 89%, specificity 60% 1
  • At 120 pg/mL threshold: sensitivity 81%, specificity 80% 1
  • Particularly high sensitivity (99%) for proven cases of neonatal invasive candidiasis 1

• Other biomarkers under investigation:

  • C-reactive protein and procalcitonin 2
  • Cytokines (IL-6, IL-8, IFN-γ, TNF-α) 2
  • Cell surface antigens (sICAM, CD64) 2

Pitfalls and Caveats

• Hypotension is not necessary for clinical diagnosis of septic shock but confirms the diagnosis when present 1
• Blood culture sensitivity is limited in neonates due to small sample volumes (<1 mL) 1
• Waiting for confirmatory laboratory tests before intervention is discouraged 1
• Consider viral etiologies (enteroviruses, parechoviruses, HSV) in the differential diagnosis 2
• Antibiotic overuse is a significant concern; very few neonates with suspected sepsis actually have confirmed sepsis 3
• Lumbar puncture may be deferred if a non-infectious condition is believed to be responsible for the infant's signs and there are no maternal risk factors for sepsis 1