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
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Benzylpenicillin (early-onset)[1] | Beta-lactam antibiotic | Not applicable — neonatal guideline | 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 | Not applicable — neonatal guideline | 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 | Not applicable | 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 | Not applicable | 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 | Not applicable | 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 | Not applicable | 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 |
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
- Neonatal infection can deteriorate quickly — take any concerns about poor feeding, lethargy, fever, or breathing difficulty seriously and seek same-day review[1]
- If antibiotic is stopped at 36 h with negative cultures, observation continues — return immediately for any new symptoms[1]
- 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.