Neonatal infection

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.

References

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