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Neonatal Sepsis - MBBS Final Year Paediatrics

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Definition

• Incidence (India, NNPD data): ~30 per 1000 live births; mortality ~4.1%
• Neonates have approximately twice the risk of serious bacterial infection compared to infants aged 4-8 weeks
• It is the most common cause of neonatal cardiorespiratory distress

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Classification

Very Late-Onset Sepsis - Some classify infections after 90 days separately, mainly in preterm NICU babies.

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Causative Organisms

Early-Onset Sepsis (India - important for exam)

• Gram-negative organisms predominate in India (unlike the West where GBS predominates)
• Klebsiella pneumoniae, E. coli - most common in India
• Group B Streptococcus (GBS, Streptococcus agalactiae) - most common in the West
• Listeria monocytogenes
• Staphylococcus aureus

Late-Onset Sepsis

• Staphylococcus aureus (MRSA in NICU)
• Coagulase-negative Staphylococci (CoNS) - esp. in preterm/VLBW with lines
• Klebsiella, Pseudomonas, Acinetobacter
• Candida species - in immunocompromised/preterm

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Risk Factors

Maternal / Perinatal Risk Factors (EOS)

• Prolonged rupture of membranes (PROM >18 hours)
• Maternal fever / chorioamnionitis
• GBS-positive vaginal swabs in mother
• Fetal distress / birth asphyxia
• Prematurity / low birth weight (LBW)
• Maternal urinary tract infection
• Traumatic delivery / multiple vaginal examinations

Neonatal Risk Factors (LOS)

• Prematurity / VLBW (<1500 g)
• Invasive procedures (central lines, intubation)
• Prolonged hospital stay / NICU admission
• Parenteral nutrition
• Immunodeficiency

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Pathophysiology

• Immature cutaneous and mucosal barriers
• Low T-cell and B-cell concentrations with absent antigenic memory
• Maternal IgG (passive immunity) reaches nadir at 2-3 months of age
• Depressed cell-mediated immunity (susceptibility to viral/fungal infections)
• Neutrophil functional defects (chemotaxis, phagocytosis)

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Clinical Features

General (The "sick-looking" neonate)

Important exam point: Nuchal rigidity and Kernig/Brudzinski signs are present in only a small minority of neonates with meningitis - DO NOT rely on them to exclude meningitis in neonates!

Tachypnea and respiratory distress can be the only sign of meningitis or UTI in a neonate.

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Investigations

Sepsis Screen (essential for exam)

Gold Standard Investigation

• Blood culture - gold standard for diagnosis; however only ~50% of clinically septic neonates have positive cultures

Other Investigations

• CBC with differential - neutropenia, thrombocytopenia, toxic granules, Döhle bodies
• Lumbar puncture + CSF analysis - mandatory in all suspected neonatal sepsis (threshold is lower than older infants); send for cell count, protein, glucose, culture
• Urine culture (catheter or suprapubic aspiration)
• Chest X-ray - pneumonia
• Blood glucose - hypoglycemia
• ABG - metabolic acidosis, hypoxia
• Coagulation profile - DIC (gram-negative sepsis more likely to cause thrombocytopenia)
• Procalcitonin - rising biomarker, but physiologically elevated in first 48 hours of life normally
• Serum bilirubin

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Differential Diagnosis

• Congenital heart disease (ductal-dependent lesions - may mimic septic shock)
• TORCH infections (Toxoplasmosis, Rubella, CMV, Herpes, Others)
• Respiratory distress syndrome (RDS) / TTN
• Inborn errors of metabolism
• Congenital adrenal hyperplasia
• Intracranial hemorrhage
• Necrotizing enterocolitis (NEC)

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Management

Supportive Care (ABCDE approach)

• Maintain thermoneutral environment
• IV access, fluid resuscitation (10 mL/kg normal saline boluses for shock)
• Oxygen supplementation / mechanical ventilation if required
• Treat hypoglycemia (IV dextrose)
• Correct metabolic acidosis
• Blood products for DIC / thrombocytopenia

Empirical Antibiotic Therapy (start BEFORE culture results)

AVOID ceftriaxone in neonates - displaces bilirubin from albumin and can cause kernicterus!

• Replace gentamicin with Cefotaxime or Ceftazidime (50 mg/kg) - better CSF penetration

• Add Vancomycin

• Add IV Acyclovir

• Amphotericin B or Fluconazole

Duration of Antibiotics

• Culture-positive sepsis without meningitis: 10-14 days
• Meningitis: 14-21 days
• Culture-negative but clinically improved: 7-10 days

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Prevention

Intrapartum Antibiotic Prophylaxis (IAP) for GBS

• Penicillin G / Ampicillin / Cefazolin given ≥4 hours before delivery = adequate IAP
• Indications: GBS-positive vaginal swab, prior GBS-affected infant, GBS bacteriuria in current pregnancy, unknown status with risk factors

Other Prevention Strategies

• Handwashing (most important infection control measure in NICU)
• Minimize invasive procedures
• Encourage exclusive breastfeeding
• Kangaroo mother care for LBW/preterm
• Chlorhexidine cord care
• Antenatal corticosteroids reduce risk in preterm

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Risk Assessment for GBS EOS (AAP Algorithm)

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Complications

• Meningitis - especially with late-onset sepsis; commoner with GBS and gram-negative organisms
• Disseminated Intravascular Coagulation (DIC)
• Septic shock - more common with early-onset sepsis
• Pneumonia / respiratory failure
• Pulmonary hypertension
• Renal failure
• Neurodevelopmental sequelae - cerebral palsy, hearing loss, developmental delay (especially post-meningitis)
• Death - still a major cause of neonatal mortality

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High-Yield Exam Points

1. Gold standard: Blood culture (positive in only ~50% of clinical sepsis)
2. Avoid ceftriaxone in neonates - risk of kernicterus
3. Empiric treatment: Ampicillin + Gentamicin (first line)
4. Hypothermia (not just fever) is a danger sign in preterm neonates
5. GBS = most common cause globally (West); Klebsiella/E. coli = most common in India
6. Meningitis signs are unreliable in neonates - always do LP
7. LOS is more associated with meningitis; EOS with septic shock
8. Sepsis screen = 2 or more positive parameters
9. Neonates with suspected sepsis should always be admitted and started on empiric IV antibiotics
10. Add Acyclovir for HSV encephalitis risk; Add Vancomycin for MRSA risk in NICU

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