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Sepsis in newborn

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1. DEFINITION AND SCOPE

  • Definition: A clinical syndrome characterized by a dysregulated host response to bloodstream infection in the first 28 days of life.
  • Clinical Scope: Encompasses septicemia, meningitis, pneumonia, arthritis, osteomyelitis, and urinary tract infections. Superficial infections (e.g., conjunctivitis, oral thrush) are excluded.
  • Significance: A major cause of neonatal mortality globally; nearly 25% of neonatal deaths are attributable to sepsis.

2. CLASSIFICATION

FeatureEarly-Onset Sepsis (EOS)Late-Onset Sepsis (LOS)
Onset≤ 72 hours of life> 72 hours of life
SourceMaternal genital tract (Ascending/Vertical)Hospital (HAI) or Community environment
Common OrganismsKlebsiella, E. coli, GBSCONS, S. aureus, Klebsiella, Candida
Risk FactorsPerinatal/Maternal factorsPrematurity, invasive lines, poor hygiene
PresentationFulminant, respiratory distress, pneumoniaInsidious, septicemia, focal (meningitis)

3. ETIOLOGY (INDIAN CONTEXT)

  • Gram-negative (66%): Acinetobacter spp. (22%), Klebsiella spp. (17%), E. coli (14%). High rates of multi-drug resistance (MDR) are prevalent.
  • Gram-positive: Coagulase-negative Staphylococcus (15%), Staphylococcus aureus (12%), Enterococcus spp. (6%).
  • Fungal: Candida albicans and non-albicans (Common in VLBW or with prolonged broad-spectrum antibiotics).

4. RISK FACTORS

  • Maternal/Perinatal (EOS):
    • Pre-labor rupture of membranes (PROM) > 24 hours.
    • Intrauterine inflammation/infection (Triple I): Maternal fever >39°C or >38°C with fetal tachycardia/leukocytosis.
    • Foul-smelling liquor and multiple unclean vaginal examinations (>3).
    • Prolonged labor (sum of 1st and 2nd stages > 24 hours).
    • Severe perinatal asphyxia (Apgar < 4 at 1 min).
  • Neonatal/Environmental (LOS):
    • Prematurity and Low Birth Weight (highest risk).
    • Invasive procedures: Mechanical ventilation, central lines (CLABSI), parenteral fluids.
    • Community factors: Poor cord care, bottle feeding, prelacteal feeds.

5. CLINICAL FEATURES

  • Nonspecific Signs: Lethargy, poor cry, refusal to suck, “not doing well,” hypothermia (common in preterms) or fever.
  • System-Specific:
    • Respiratory: Tachypnea, grunting, chest retractions, apnea, gasping.
    • Cardiovascular: Poor perfusion (prolonged capillary refill), tachycardia/bradycardia, hypotension, shock.
    • CNS: Bulging anterior fontanelle, vacant stare, high-pitched cry, seizures, neck retraction (Meningitis).
    • GIT: Increased gastric residuals, vomiting, abdominal distension, paralytic ileus.
    • Hemat/Metabolic: Petechiae, purpura, direct hyperbilirubinemia, hypo/hyperglycemia, metabolic acidosis.

6. INVESTIGATIONS

  • Blood Culture (Gold Standard): 1 ml blood in 5-10 ml broth. Automated systems (BACTEC/BACT-ALERT) can detect growth within 12-24 hours. Keep for 72 hours before reporting sterile.
  • Sepsis Screen (Positive if ≥ 2 parameters abnormal):
    1. TLC: < 5,000 or > 20,000/mm³.
    2. ANC: < 1,800/mm³ (as per Manroe/Mouzinho charts).
    3. I/T Ratio: > 0.2 (Immature to Total Neutrophils).
    4. Micro-ESR: > 15 mm in 1st hour.
    5. CRP: > 1 mg/dl (High negative predictive value).
  • Lumbar Puncture (CSF): Mandatory in all LOS, symptomatic sepsis, or if blood culture is positive. Normal CSF values: Term (Cells 0-32, Protein 20-170 mg/dl); Preterm (Cells 0-44, Protein 54-370 mg/dl).
  • Radiology: Chest X-ray (respiratory distress), Abdominal X-ray (distension/NEC), Neuroimaging (meningitis complications).
  • Biomarkers: Procalcitonin (PCT) - age-specific cutoffs; Serum Amyloid A (promising but not routine).

7. MANAGEMENT

A. Supportive Care

  • Thermal Neutral Environment (TNE): Avoid hypo/hyperthermia.
  • Respiratory Support: Maintain Saturation 91-95%.
  • Hemodynamics: Volume expansion (10 ml/kg crystalloids) and judicious inotropes.
  • Metabolic: Monitor glucose and treat acidosis.

B. Empirical Antibiotic Therapy

  • Community-Acquired: Ampicillin/Penicillin + Gentamicin.
  • Hospital-Acquired (HAI): Beta-lactam (e.g., Piperacillin-Tazobactam) + Aminoglycoside (e.g., Amikacin).
  • Suspected Staphylococcal: Cloxacillin or Vancomycin (if MRSA).
  • Meningitis: Third-generation cephalosporins (e.g., Cefotaxime) were traditional, but high resistance (60-70%) now limits use.
  • Reserve Drugs: Meropenem, Colistin, Linezolid (Avoid empiric use; reserve for proven sensitivity).

C. Duration of Therapy

  • Meningitis: 21 days.
  • Culture Positive (Septicemia): 14 days.
  • Culture Negative (Clinical Sepsis): 5–7 days.
  • Screen Negative/Rule out: 48–72 hours.

8. ADJUNCTIVE THERAPY AND PREVENTION

  • Exchange Transfusion: May reduce mortality in sepsis with sclerema by removing cytokines.
  • Immunotherapy: IVIG/G-CSF currently not recommended due to lack of proven mortality benefit.
  • Prevention: Handwashing (most important for LOS), breastfeeding/colostrum, rational antibiotic use (Antibiotic Stewardship), and aseptic bundle care for invasive lines.

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