Built on West Midlands Neonatal Guidelines 2025–28 (NICE NG195) · Kaiser Permanente EOS calculator · AAP EOS guidance · Baylor Guidelines for Acute Care of the Neonate
Early-onset sepsis (EOS) is invasive bacterial infection presenting in the first 72 hours of life, acquired around the time of birth. Group B streptococcus (GBS) and Escherichia coli are the predominant organisms. Because early signs are non-specific and deterioration can be rapid, care balances two goals: treat genuinely infected infants promptly, and avoid unnecessary antibiotics (and separation from mother) in the large number of at-risk but uninfected babies. Structured risk assessment — the NICE framework and/or a validated EOS calculator — supports that balance.
Untreated EOS is rapidly fatal, yet blanket antibiotic use exposes many well infants to harm (microbiome disruption, resource use, mother–baby separation). The commonest errors are delaying antibiotics in a sick baby and, conversely, prolonged "just-in-case" courses when cultures are negative and the baby is well.
EOS is culture-confirmed or clinically diagnosed invasive infection (bacteraemia, meningitis, or pneumonia) with onset within the first 72 hours of life. "Culture-negative/clinical sepsis" describes a symptomatic infant treated as infected despite sterile cultures.
Shared vocabulary for the EOS pathway.
| Term | Definition | Practical note |
|---|---|---|
| EOS | Invasive infection with onset <72 h of life. | GBS and E. coli predominate. |
| Red-flag factor | High-risk feature mandating investigation + antibiotics. | e.g., confirmed infection in a co-twin; shock; need for CPR/ventilation; seizures. |
| IAP | Intrapartum antibiotic prophylaxis (for maternal GBS). | Reduces early-onset GBS; does not prevent late-onset GBS. |
| EOS calculator (KP-SRC) | Validated tool estimating EOS probability to guide antibiotics in ≥34–35-week infants. | NICE-endorsed alternative for eligible well babies; pair with observation. |
| Culture-negative sepsis | Symptomatic infant treated as infected despite sterile cultures. | Keep courses short if cultures negative and baby well. |
A single red flag, or two or more other risk factors/clinical indicators, triggers investigation and antibiotics.
| Category | Factors |
|---|---|
| Red flag | Suspected/confirmed infection in another baby of a multiple pregnancy. |
| Other risk factors | Previous baby with invasive GBS; maternal GBS colonisation/bacteriuria/infection this pregnancy; preterm birth (<37 wk) after spontaneous labour; confirmed rupture of membranes >18 h before preterm birth; term pre-labour rupture >24 h; intrapartum fever >38°C with suspected/confirmed bacterial infection; clinical chorioamnionitis. |
Red-flag indicators mandate immediate treatment; non-red-flag indicators are weighed with risk factors.
| Category | Indicators |
|---|---|
| Red flag | Apnoea; need for CPR; seizures; need for mechanical ventilation; signs of shock. |
| Other | Altered behaviour/tone (floppiness); feeding difficulty/intolerance (distension, vomiting, high aspirates); abnormal heart rate; respiratory distress; hypoxia/cyanosis; jaundice within 24 h; signs of encephalopathy or PPHN; temperature <36°C or >38°C unexplained; unexplained bleeding/thrombocytopenia/coagulopathy; hypo/hyperglycaemia; metabolic acidosis (base excess ≥10). |
Default regimen follows Baylor Ed. 33 (Table 9-4); the UK alternative is listed last. Doses by gestation and postnatal age, and drug levels, are tabulated in 8.2.
| Setting | First-line regimen | Notes |
|---|---|---|
| Default (Baylor Ed. 33) | Ampicillin 100 mg/kg every 8 h + an aminoglycoside — Baylor uses amikacin; gentamicin (e.g., 4 mg/kg every 24 h at 35–43 weeks, ≤7 days old) is the alternative. | Baylor's amikacin choice follows its local antibiogram, not a claim of superiority — pick the aminoglycoside by your own susceptibility data. 48-hour rule-out; 7–10 days of organism-specific therapy if the culture is positive. |
| Meningitis suspected | Ampicillin + ceftazidime at meningeal doses. | Organism-specific duration; repeat CSF 24–48 h into therapy. Avoid ceftriaxone in neonates. |
| Umbilical infection | Flucloxacillin + gentamicin. | Cover staphylococci; de-escalate on cultures. |
| Other sources: UK / NICE | Benzylpenicillin 25 mg/kg 12-hourly (8-hourly if very ill) + gentamicin 5 mg/kg per local interval. | Add cefotaxime for suspected/confirmed Gram-negative sepsis or meningitis; stop benzylpenicillin if Gram-negative confirmed. |
Above 35 0/7 weeks: any infant with signs of sepsis gets a CBC, blood and CSF cultures, and antibiotics. If the mother had a fever above 38 °C before delivery or within 24 hours after, review the obstetric history — and where intra-amniotic infection, endometritis or another systemic maternal infection is judged present, use the Neonatal Early-Onset Sepsis Risk Calculator to decide. Empiric antibiotics are not given unless the calculator recommends them, but vital signs every 4 hours are, even in a well-looking infant. With rupture of membranes beyond 18 hours but no signs of infection in mother or infant: observe in hospital for 48 hours. Healthy-appearing infants need paediatric follow-up within 2–5 days of discharge.
Below 34 6/7 weeks: evaluate and treat for prolonged rupture of membranes, maternal fever, intra-amniotic infection, unexplained premature labour, maternal antibiotics for suspected bacterial infection, or any sign of sepsis. If none of these is present and delivery was by caesarean without labour and with intact membranes, no evaluation is needed unless sepsis is suspected clinically. Well-appearing at-risk preterm infants get a CBC and blood culture — the lumbar puncture is at the attending's discretion — and meningeal doses of antibiotics. A VLBW infant whose course and evaluation make sepsis very unlikely may not need an LP at all.
CRP and procalcitonin have little to no value in confirming or excluding early-onset infection and are not recommended for that purpose. (They retain a limited role in late-onset sepsis — a CRP below 1 mg/dL at 24 hours after the workup began makes bacterial infection unlikely and can shorten antibiotic exposure.) Treating culture-negative sepsis beyond 36–48 hours is discouraged; in term infants, stop once the blood culture is sterile at 24–48 hours of incubation. Meningeal doses if the CSF is abnormal, could not be obtained, or a Gram-negative organism is suspected; non-meningeal doses if the CSF is normal. Repeat a positive blood culture every 24 hours until two consecutive sterile cultures, and repeat the CSF 24–48 hours into therapy to document sterility.
Serial observation is central — the trajectory guides both starting and stopping.
| Parameter | Frequency | Target / watch | Action if abnormal |
|---|---|---|---|
| Vital signs / clinical status | ≥12 h if observing (1 h, 2 h, then 2-hourly) | Stable, feeding well | New indicator → investigate and treat. |
| Blood culture | At 36–48 h and as results return | Negative | Positive → continue/tailor; consider LP. |
| CRP | Not used for EOS decisions by default (NICE units: baseline + 18–24 h) | — | Base stopping on cultures and the clinical course. |
| Gentamicin levels | Per TDM protocol. Baylor Ed. 33: when treatment will exceed 48 h or renal function is abnormal — peak and trough around the third dose (sooner with acute kidney injury), then at least weekly | Therapeutic/safe trough. Peak 30 min after the infusion ends (efficacy); trough just before the next dose (safety); follow BUN and creatinine | Adjust dose/interval. Doses are chosen by PMA, postnatal age and weight, and should be updated for weight weekly; involve pharmacy in renal dysfunction and ID for complicated infections. Vancomycin: trough 8–20 mcg/mL by organism, MIC and site; check levels only with renal dysfunction, treatment failure, or on specialist request — at appropriate doses alone it is not nephrotoxic in children. |
| Glucose / acid–base | As indicated | Normal | Support; reconsider severity. |
The recurring errors in EOS management.
| Mistake | Why it harms | Better practice |
|---|---|---|
| Delaying antibiotics in a sick baby. | EOS can be rapidly fatal. | Culture then antibiotics within 1 hour; don't wait for tests. |
| Relying on a single normal CRP/WCC to exclude sepsis. | False reassurance. | Use the whole clinical picture and cultures. |
| Prolonged antibiotics with negative cultures. | Microbiome harm, resistance, separation. | Apply the 36–48-hour stop rule. |
| Using ceftriaxone in neonates. | Bilirubin/calcium risks. | Use cefotaxime for Gram-negative/CNS cover. |
| Forgetting HSV. | Untreated HSV is devastating. | Add aciclovir when features suggest it. |
| Routine urine culture / surface swabs in EOS. | Low yield, misleading. | Blood culture ± LP; swabs only for localised signs. |