Sepsis in newborn

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.

Feature	Early-Onset Sepsis (EOS)	Late-Onset Sepsis (LOS)
Onset	≤ 72 hours of life	> 72 hours of life
Source	Maternal genital tract (Ascending/Vertical)	Hospital (HAI) or Community environment
Common Organisms	Klebsiella, E. coli, GBS	CONS, S. aureus, Klebsiella, Candida
Risk Factors	Perinatal/Maternal factors	Prematurity, invasive lines, poor hygiene
Presentation	Fulminant, respiratory distress, pneumonia	Insidious, septicemia, focal (meningitis)

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).

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.

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.

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).

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.

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).

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.