Neonatal sepsis

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Neonatal Sepsis

Definition

Neonatal sepsis is a systemic infection occurring in the first 28 days of life. It is the most common cause of neonatal cardiorespiratory distress and carries significant morbidity and mortality. - Tintinalli's Emergency Medicine, p.775

Classification: Early-Onset vs. Late-Onset

Feature	Early-Onset (EOS)	Late-Onset (LOS)
Timing	First 7 days of life	After 7 days of life
Onset	Fulminant	More gradual
Risk factors	Maternal/perinatal (fever, GBS, prolonged ROM, fetal distress)	Less linked to perinatal risk factors
Common complications	Septic shock, neutropenia	Meningitis more common
Typical organisms	GBS, E. coli, Listeria	GBS (meningitis), nosocomial organisms

Tintinalli's Emergency Medicine, p.775

Causative Organisms

Pathogens reflect organisms colonizing the female genital tract and nasal mucosa of caregivers:

Gram-positive: Group B Streptococcus (GBS) - the most common bacterial pathogen overall; causes severe cardiorespiratory instability + meningitis in ~30% of cases
Gram-negative enteric: E. coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae
Other: Listeria monocytogenes (gram-positive rod, ampicillin-sensitive)
Viral: Herpes simplex virus (HSV) - fulminant in neonates; active maternal lesions at delivery are an indication for cesarean section
Fungal: Candida spp. - especially in preterm/NICU infants (cephalosporins predispose to invasive candidiasis)

In the US, GBS and E. coli represent the two most common newborn pathogens. - Rosen's Emergency Medicine, p.1712; Miller's Anesthesia, p.11455

Signs & Symptoms

Neonatal sepsis is a great masquerader - signs are non-specific. Nuchal rigidity and Kernig/Brudzinski signs are present in only a minority of neonates with meningitis.

Temperature:

Fever = rectal temp ≥38°C (100.4°F)
Hypothermia = rectal temp <36.5°C (97.7°F)
Either temperature instability signals serious infection

Other features (Table 116-3):

CNS: Lethargy, irritability, seizures
Respiratory: Apnea, tachypnea, grunting, respiratory distress
GI: Vomiting, poor feeding, gastric distention, diarrhea
Skin: Jaundice, rashes, petechiae, poor cutaneous perfusion
Metabolic: Hypoglycemia, metabolic acidosis
Cardiovascular: Hypotension
Tintinalli's Emergency Medicine, p.775; Miller's Anesthesia, p.11455

Risk Factors (Maternal/Perinatal)

GBS-positive vaginal swabs
Maternal fever or chorioamnionitis
Prolonged rupture of membranes (>18 hours)
Preterm birth (<37 weeks)
Fetal distress
Active maternal HSV lesions

Differential Diagnosis

Critical neonatal illness mimicking sepsis:

Ductal-dependent congenital heart disease (e.g., hypoplastic left heart, critical coarctation) - presents with shock as ductus closes in first week
Inborn errors of metabolism
Congenital adrenal hyperplasia
Intracranial hemorrhage
Abdominal catastrophe (malrotation, volvulus, NEC)

Tintinalli's Emergency Medicine, Table 116-2

Investigations (Sepsis Workup)

Threshold for a full sepsis workup is lower in neonates than in older infants. All neonates with suspected sepsis require:

Blood culture (before antibiotics)
Urine culture (catheter specimen)
CSF analysis - cell count, glucose, protein, Gram stain, culture
CBC with differential - neutropenia, thrombocytopenia, elevated immature-to-total neutrophil ratio
CRP / Procalcitonin - inflammatory markers (note: only ~50% of neonates thought to be septic have positive cultures)
Blood glucose - hypoglycemia is common
Chest X-ray - if respiratory signs present

Miller's Anesthesia, p.11455; Red Book 2021

Treatment

General Principles

Admit all neonates with suspected sepsis to hospital
Initiate empiric IV antibiotics immediately after cultures obtained
Do NOT delay treatment to await culture results

Empiric Antibiotic Regimens

Early-onset sepsis (≤7 days):

Ampicillin 50-100 mg/kg IV + Aminoglycoside (Gentamicin 2.5-4 mg/kg IV)
- Covers GBS, Listeria (ampicillin) and E. coli/gram-negatives (gentamicin)

If gram-negative meningitis strongly suspected:

Replace gentamicin with Cefotaxime 50 mg/kg (better CNS penetration)
⚠️ Avoid ceftriaxone in neonates - displaces bilirubin and can cause kernicterus

Late-onset sepsis (8-28 days, no meningitis):

Ampicillin + gentamicin OR cefotaxime

Late-onset with suspected meningitis:

Ampicillin + cefotaxime (NOT gentamicin if meningitis suspected)

Infants 29-90 days:

Ceftriaxone is now appropriate; add vancomycin if critical illness or meningitis

Add IV Acyclovir when:

Maternal history of herpes
CSF shows lymphocytosis + RBCs (nontraumatic LP)
Neonate appears ill

Confirmed GBS infection:

Penicillin G or Ampicillin (definitive therapy)
Tintinalli's Emergency Medicine, p.775; Red Book 2021, p.1097; Rosen's Emergency Medicine, p.1712

Duration of Treatment

Bacteremia without focus or isolated UTI: 10 days IV
Uncomplicated meningitis: ≥14 days IV
Complicated meningitis: longer courses

GBS Prevention (Maternal Screening)

Rectovaginal culture at 35-37 weeks gestation
GBS-positive mothers receive intrapartum IV penicillin prophylaxis
Active maternal HSV lesions: cesarean section
NAATs available for rapid intrapartum testing (sensitivity reduced without enrichment step)
Red Book 2021, p.1097; Textbook of Family Medicine

Recent Evidence (2024-2025)

Three recent high-quality publications are relevant:

Antibiotic strategies for neonatal sepsis - Soni P et al., 2025 - Meta-analysis on efficacy and emerging resistance patterns in neonatal sepsis (PMID: 40555905). Important given growing concern about ampicillin-resistant E. coli in EOS.
Molecular assays for neonatal sepsis diagnosis - Dierikx TH et al., Cochrane 2025 - Diagnostic test accuracy review of NAATs and molecular methods vs. conventional culture (PMID: 40105375). Supports use of molecular diagnostics where culture sensitivity is limited (~50%).
Platelet parameters as biomarkers - Tong X et al., 2025 - Thrombocytopenia and platelet indices as accessible biomarkers for early sepsis detection (PMID: 41225524).

Key Points Summary


Most common cause of neonatal cardiorespiratory distress	Sepsis
Most common bacterial pathogen	Group B Streptococcus
2nd most common	E. coli
First-line empiric treatment	Ampicillin + Gentamicin
Avoid in neonates	Ceftriaxone (kernicterus risk)
When to add acyclovir	Maternal HSV history, lymphocytic CSF, ill-appearing infant
Positive culture rate	~50% of clinically suspected cases
Meningitis antibiotic	Ampicillin + Cefotaxime

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