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Neonatology · NICE

Neonatal infection

NICE
A
Source:NICE Guideline NG195 — Neonatal Infection: Antibiotics for Prevention and Treatment (2021)WHO Guidelines for Neonatal Sepsis Management (2021)AAP/CDC GBS Prevention (2021)
Verified Apr 2026
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Red Flags

  • Any 'red' clinical signs (apnoea, severe respiratory distress, persistent hypoxia, neonatal encephalopathy, seizure, septic shock) — start IV antibiotic within 1 h of decision; admit[1]
  • Suspected meningitis (bulging fontanelle, hyperexcitability, posturing, focal seizure) — LP if stable; broad-spectrum IV antibiotics with CNS penetration; head ultrasound[1]
  • Maternal chorioamnionitis or intrapartum sepsis — start neonatal antibiotic without waiting for symptoms; risk factor-based approach[1]
  • Late-onset sepsis (≥72 h) with central line, prematurity, surgery — broader cover including coagulase-negative Staphylococcus and Gram-negative[1]

First-line treatment

Interventions

  • Intrapartum antibiotic prophylaxis (IAP) for GBS prevention[1]
    Maternal GBS-positive screen at 35–37 weeks, prior infant with GBS disease, GBS bacteriuria in pregnancy, intrapartum fever ≥38°C, or unknown status with risk factors — give IV penicillin G or ampicillin during labour; reduces early-onset GBS sepsis
  • Antibiotic stewardship[1]
    Stop antibiotic at 36 h if blood culture negative, CRP <10 mg/L, baby clinically well; do not extend solely on 'covering all bases'; document plan
  • Early-onset (<72 h) empirical regimen[1]
    Benzylpenicillin (or ampicillin in some pathways) + gentamicin IV; covers GBS and gram-negatives; review at 36 h and 48 h with cultures
  • Late-onset (≥72 h) empirical regimen[1]
    Cover for coagulase-negative Staphylococcus, Gram-negative, and consider central-line-associated; flucloxacillin + gentamicin or piperacillin-tazobactam; vancomycin if MRSA risk; broad cover in NICU outbreak settings

First-line drug therapy

DrugClassAdultPaediatricNotes
Benzylpenicillin (early-onset)[1]Beta-lactam antibioticNot applicable — neonatal guidelineTerm: 50 mg/kg IV every 12 h × first week; preterm or per gestational age and corrected protocolFirst-line for early-onset GBS sepsis in many UK pathways; combine with gentamicin; alternative ampicillin in WHO and US protocols
Gentamicin (early-onset)[1]AminoglycosideNot applicable — neonatal guidelineTerm: 5 mg/kg IV every 36 h initially; preterm extended interval per gestational age; trough level before 3rd doseCombines with penicillin/ampicillin for synergy; renal monitoring if course extends; avoid prolonged exposure where possible
Ampicillin + cefotaxime (alternative for early-onset)[1]Aminopenicillin + third-generation cephalosporinNot applicableAmpicillin 50 mg/kg IV every 12 h; cefotaxime 50 mg/kg IV every 12 hAlternative regimen where local resistance favours; consider in suspected gram-negative sepsis or meningitis
Flucloxacillin + gentamicin (late-onset)[1]Beta-lactamase-stable penicillin + aminoglycosideNot applicableFlucloxacillin 25–50 mg/kg IV every 8 h; gentamicin per protocolLate-onset cover for staphylococcal and gram-negative infection; expand to vancomycin and meropenem in NICU outbreak or critical illness
Vancomycin (suspected MRSA / coagulase-negative Staph)[1]GlycopeptideNot applicable10–15 mg/kg IV every 8–12 h (per gestational age); TDM target trough 10–15Late-onset NICU sepsis with central line; trough monitoring; renal function review
Acyclovir (suspected HSV)[1]AntiviralNot applicable20 mg/kg IV every 8 h × 14–21 days per disease typeAdd empirically to antibiotic in any neonate with seizure, hepatitis, sepsis-like presentation, or vesicular rash; HSV PCR on blood, CSF, surface swabs
Benzylpenicillin (early-onset)[1]
Beta-lactam antibiotic
Adult
Not applicable — neonatal guideline
Paediatric
Term: 50 mg/kg IV every 12 h × first week; preterm or per gestational age and corrected protocol
First-line for early-onset GBS sepsis in many UK pathways; combine with gentamicin; alternative ampicillin in WHO and US protocols
Gentamicin (early-onset)[1]
Aminoglycoside
Adult
Not applicable — neonatal guideline
Paediatric
Term: 5 mg/kg IV every 36 h initially; preterm extended interval per gestational age; trough level before 3rd dose
Combines with penicillin/ampicillin for synergy; renal monitoring if course extends; avoid prolonged exposure where possible
Ampicillin + cefotaxime (alternative for early-onset)[1]
Aminopenicillin + third-generation cephalosporin
Adult
Not applicable
Paediatric
Ampicillin 50 mg/kg IV every 12 h; cefotaxime 50 mg/kg IV every 12 h
Alternative regimen where local resistance favours; consider in suspected gram-negative sepsis or meningitis
Flucloxacillin + gentamicin (late-onset)[1]
Beta-lactamase-stable penicillin + aminoglycoside
Adult
Not applicable
Paediatric
Flucloxacillin 25–50 mg/kg IV every 8 h; gentamicin per protocol
Late-onset cover for staphylococcal and gram-negative infection; expand to vancomycin and meropenem in NICU outbreak or critical illness
Vancomycin (suspected MRSA / coagulase-negative Staph)[1]
Glycopeptide
Adult
Not applicable
Paediatric
10–15 mg/kg IV every 8–12 h (per gestational age); TDM target trough 10–15
Late-onset NICU sepsis with central line; trough monitoring; renal function review
Acyclovir (suspected HSV)[1]
Antiviral
Adult
Not applicable
Paediatric
20 mg/kg IV every 8 h × 14–21 days per disease type
Add empirically to antibiotic in any neonate with seizure, hepatitis, sepsis-like presentation, or vesicular rash; HSV PCR on blood, CSF, surface swabs

Safety-net

  1. Neonatal infection can deteriorate quickly — take any concerns about poor feeding, lethargy, fever, or breathing difficulty seriously and seek same-day review[1]
  2. If antibiotic is stopped at 36 h with negative cultures, observation continues — return immediately for any new symptoms[1]
  3. GBS-positive mothers should receive intrapartum antibiotic prophylaxis — discuss this with your maternity team[1]

Referral criteria

  • Any 'red' or 'amber' clinical signs in newbornNeonatal admission and IV antibiotic[1]
  • Suspected meningitis or significant sepsisTertiary neonatal unit with ITU capability[1]
  • Late-onset sepsis with central line, prematurity, or surgical historyNICU specialist team; targeted broad-spectrum antibiotic[1]
  • Recurrent infection or unusual organisms (Listeria, Enterococcus, Candida)Infectious diseases / NICU specialist for tailored regimen[1]

Clinical summary

Risk-based assessment, empirical antibiotic choice, and management of early-onset and late-onset neonatal sepsis and meningitis.

References

  1. 1.NICE Guideline NG195 — Neonatal Infection: Antibiotics for Prevention and Treatment (2021); WHO Guidelines for Neonatal Sepsis Management; AAP/CDC GBS Prevention (2021)

On this page

  • Red flags
  • First-line treatment
  • Safety-net
  • Referral
  • References