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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Early-onset sepsis (EOS, within 72 h): GBS most common; E. coli second
- Late-onset sepsis (LOS, >72 h): CoNS, S. aureus, Gram-negatives, Candida (preterm)
- Presentation is NONSPECIFIC: temperature instability, poor feeding, lethargy, respiratory distress, apnoea, mottled skin
- Risk factors: preterm, PROM >18 h, maternal GBS colonisation, maternal fever >38C in labour, chorioamnionitis
- Empirical antibiotics per NICE NG195: benzylpenicillin + gentamicin (EOS). Start within 1 hour of suspicion
- Review at 36–48 h — stop if cultures negative and infant well
Overview
Neonatal sepsis is a clinical syndrome of systemic infection in the first 28 days of life. Early-onset sepsis (EOS, within 72 hours) is acquired vertically from maternal genital tract organisms, with Group B Streptococcus and Escherichia coli being the most common pathogens. Late-onset sepsis (LOS, >72 hours) is typically nosocomial, particularly in preterm infants with central lines. The clinical presentation is notoriously nonspecific. A low threshold for investigation and empirical antibiotic treatment is essential, as deterioration can be rapid.
Epidemiology
The incidence of EOS in the UK is approximately 0.9 per 1,000 live births. GBS accounts for approximately 50% of EOS cases. Prematurity is the single strongest risk factor. Maternal risk factors include GBS colonisation or bacteriuria, PROM >18 hours, preterm labour, intrapartum fever, and previous infant with GBS disease. Late-onset sepsis affects up to 20% of VLBW infants in NICUs. Mortality from neonatal sepsis is approximately 10% overall, higher with Gram-negative and fungal infections.
Clinical Features
Symptoms
Temperature instability — fever (>38C) or hypothermia (<36C) — hypothermia is more suggestive in neonates
Poor feeding, feed intolerance, or vomiting
Lethargy, irritability, or reduced responsiveness
Respiratory distress: tachypnoea, grunting, nasal flaring, recessions
Apnoeic episodes (especially in preterm)
Abdominal distension (consider NEC in LOS)
Seizures
Signs
Mottled or pale skin, capillary refill >3 seconds
Tachycardia or bradycardia
Hypotension (late sign — septic shock)
Jaundice (may be a presenting feature)
Bulging fontanelle (suggests meningitis)
Petechiae, purpura (DIC)
Investigations
First-line
Blood cultureMost important investigation — take BEFORE antibiotics. Minimum 1 mL blood
FBC with differentialNeutropenia, thrombocytopenia, raised immature:total neutrophil ratio suggest infection
CRPMay be normal initially — serial CRP at 24 h and 48 h more useful. Rising CRP supports infection
Second-line
Lumbar punctureIf clinical suspicion of meningitis, positive blood culture, or deteriorating. Do not delay antibiotics
Urine cultureClean catch or SPA — more relevant in LOS
Chest X-rayIf respiratory symptoms — differentiate pneumonia, RDS, TTN
Specialist
ProcalcitoninMore specific than CRP for bacterial infection — increasingly used to guide antibiotic duration
Blood gas and lactateMetabolic acidosis with raised lactate suggests septic shock
1
Risk assessment (EOS)
- Use NICE NG195 risk factor assessment — consider maternal and neonatal risk factors
- Red flags: clinical signs of sepsis, chorioamnionitis, preterm with PROM
- If ANY clinical concern — start antibiotics within 1 hour
2
Empirical antibiotics — EOS
- First-line: IV benzylpenicillin + IV gentamicin
- Benzylpenicillin 25 mg/kg (50 mg/kg if meningitis suspected)
- Gentamicin dose per local protocol (typically 5 mg/kg, adjusted for gestation)
- If meningitis confirmed: meningitis doses, consider cefotaxime for Gram-negatives
3
Review at 36–48 hours
- Review blood culture results and CRP
- If cultures NEGATIVE and infant well with normal CRP: STOP antibiotics
- If cultures POSITIVE: continue targeted antibiotics (7 days bacteraemia, 14–21 days meningitis)
- Do not continue antibiotics beyond 5 days without clear indication
4
Late-onset sepsis
- Empirical antibiotics per local policy — typically flucloxacillin + gentamicin
- Consider antifungals in very preterm with Candida risk factors
- Remove/replace central lines if line sepsis suspected
- LP should be performed if clinically feasible
Complications
- Meningitis: In 10–15% of EOS — prolonged treatment, hearing and neurodevelopmental follow-up
- Septic shock: Requires fluid resuscitation and inotropes
- NEC: Especially in preterm with LOS
- Long-term neurodevelopmental impairment: Following meningitis
- Death: ~10% overall, higher with Gram-negative and fungal infections in preterm
UKMLA Exam Tips
- 1GBS is the most common cause of EOS. E. coli is the most common Gram-negative cause
- 2Neonatal signs are NONSPECIFIC — low threshold to investigate and treat
- 3Empirical EOS antibiotics = benzylpenicillin + gentamicin. Start within 1 hour
- 4Review at 36–48 h: stop if cultures negative and infant well
- 5Hypothermia (<36C) is MORE suggestive of neonatal sepsis than fever — classic exam point
- 6LP should NOT delay antibiotic administration
- 7Risk factors: prematurity, PROM >18 h, maternal GBS+, intrapartum fever, chorioamnionitis
practicetest your knowledge on neonatal sepsisApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — paediatrics and beyond.
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