Note on Nelson's: Nelson's Textbook of Pediatrics is not available in the textbook library. The content below draws from the closest equivalent pediatric authorities: Red Book 2021 (AAP Committee on Infectious Diseases) - which is the definitive US pediatric infectious disease reference and whose GBS/neonatal sepsis guidelines directly mirror Nelson's content - plus Harriet Lane Handbook (Johns Hopkins, 23rd ed.), WHO 2024/2025 Recommendations for Management of Serious Bacterial Infections in Infants aged 0-59 days, and Tintinalli's/Miller's for clinical detail.
NEONATAL SEPSIS
Presentation Content - Slide by Slide
SLIDE 1 — Title
NEONATAL SEPSIS
Based on:
- Red Book 2021 - AAP Committee on Infectious Diseases (equivalent standard to Nelson's)
- Harriet Lane Handbook, 23rd Edition (Johns Hopkins)
- WHO Recommendations for Management of Serious Bacterial Infections in Infants Aged 0-59 Days (2024)
SLIDE 2 — Definition & Epidemiology
Definition:
- Neonatal sepsis is a systemic bacterial, viral, or fungal infection occurring in infants within the first 28 days of life
- Encompasses bacteremia, meningitis, urinary tract infection, and pneumonia in the newborn period
- WHO defines it as a serious bacterial infection (SBI) in infants aged 0-59 days
Epidemiology (WHO 2024):
- SBIs including sepsis, meningitis, and pneumonia contribute to >500,000 newborn deaths annually worldwide
- Neonates have approximately 2× the risk of serious bacterial infection compared to infants 4-8 weeks of age
- Only ~50% of clinically suspected neonatal sepsis cases have positive cultures
- Case-fatality rate: 1%-3% in term infants; up to 20% in preterm infants with early-onset disease (Red Book 2021)
- In 2018 (USA): Early-onset GBS disease = 0.25 cases per 1000 live births; Late-onset = 0.28 per 1000 live births (Red Book 2021)
SLIDE 3 — Classification: Early-Onset vs Late-Onset
| Feature | Early-Onset Sepsis (EOS) | Late-Onset Sepsis (LOS) |
|---|
| Timing | 0-6 days of life | 7-89 days of life |
| Peak | 95% present within 48 hours of birth | Typically 3-4 weeks of age |
| Onset character | Fulminant, rapid deterioration | Gradual, insidious |
| Common presentation | Respiratory distress, apnea, shock, pneumonia | Bacteremia, meningitis (~30% of cases) |
| Meningitis rate | 5%-10% | ~30% |
| Link to maternal factors | Strong (GBS colonization, IAP failure, PPROM) | Weaker; community/nosocomial acquisition |
| Common organisms | GBS, E. coli, Listeria | GBS (type III), CoNS, Candida |
| Mortality (GBS) | 20% in preterm; 2% in term | 8% in preterm; 1%-3% in term |
Key AAP/Red Book note: Intrapartum antibiotic prophylaxis (IAP) has reduced EOS incidence by ~80% but has had no measurable effect on late-onset GBS disease. (Red Book 2021)
SLIDE 4 — Etiology & Causative Organisms
Group B Streptococcus (GBS) - Streptococcus agalactiae
- Most common bacterial pathogen in neonatal sepsis
- Gram-positive diplococci; 10 capsular types - Types Ia, Ib, II, III, IV, V account for ~99% of infant cases in the USA
- Type III causes 30%-60% of early-onset and late-onset disease respectively
- EOS: respiratory distress, apnea, shock, pneumonia; meningitis in 5%-10%
- LOS: bacteremia, meningitis; also septic arthritis, osteomyelitis, UTI, cellulitis
- Vaginal/rectal colonization rate in pregnant women: 15%-35%
(Red Book 2021)
Escherichia coli & Gram-Negative Bacilli
- Second most common; leading cause of early-onset bacterial meningitis
- ~⅔ of E. coli bloodstream infections in very low birth weight (VLBW) infants are ampicillin-resistant (ESBL-producing)
- ESBL-producing organisms are resistant to penicillins, cephalosporins, monobactams
- Carbapenemase-producing Klebsiella pneumoniae and E. coli are emerging
- Klebsiella, Haemophilus influenzae also implicated
(Red Book 2021)
Listeria monocytogenes
- Causes sepsis and meningitis; naturally resistant to all cephalosporins
- Longer latent period - may present as late-onset sepsis
- Treatment: Ampicillin is drug of choice
Herpes Simplex Virus (HSV)
- Fulminant neonatal infection; add IV Acyclovir when suspected
- Active lesions in birth canal = indication for cesarean section
Candida species
- Important in preterm, VLBW infants in NICU
- Risk: prolonged mechanical ventilation, central lines, prolonged antibiotics
Coagulase-Negative Staphylococci (CoNS)
- Common cause of nosocomial/late-onset sepsis in NICU; associated with central venous catheters
SLIDE 5 — Risk Factors
Maternal / Perinatal Risk Factors (for EOS):
| Risk Factor | Notes |
|---|
| GBS-positive vaginal/rectal swab | Colonization rate 15%-35% |
| Intrapartum fever ≥38°C (100.4°F) | Sign of chorioamnionitis |
| Prolonged rupture of membranes ≥18 hours | Allows ascending infection |
| Preterm delivery (<37 weeks) | Immature immune system + surfactant deficiency |
| GBS bacteriuria during current pregnancy | Indicates heavy colonization |
| History of previous infant with invasive GBS | Recurrence risk |
| Maternal age <20 years | Associated with higher GBS colonization |
| Black race | Higher GBS colonization + preterm birth rates |
| Intra-amniotic infection (chorioamnionitis) | Direct fetal exposure |
| Inadequate IAP (<4 hours before delivery) | Incomplete prophylaxis |
Neonatal Risk Factors:
- Prematurity / very low birth weight (<1500 g)
- Prolonged NICU hospitalization
- Central venous catheters, endotracheal tubes
- Total parenteral nutrition
- Prior broad-spectrum antibiotic exposure (selects resistant organisms)
(Red Book 2021; Harriet Lane Handbook)
SLIDE 6 — Clinical Features
The "unwell neonate" - presentations are NON-SPECIFIC. Any sick-appearing newborn must be evaluated for sepsis.
| System | Signs & Symptoms |
|---|
| Temperature | Fever (rectal ≥38°C) or Hypothermia (<36.5°C) - both equally important |
| Respiratory | Apnea, tachypnea, grunting, nasal flaring, retractions, cyanosis |
| CNS | Lethargy, poor tone, irritability, seizures, bulging fontanelle |
| Cardiovascular | Tachycardia, hypotension, poor perfusion, mottled skin, prolonged capillary refill |
| Gastrointestinal | Poor feeding, vomiting, abdominal distension, diarrhea, hepatomegaly |
| Skin | Jaundice (especially early), petechiae, purpura, rashes |
| Metabolic | Hypoglycemia, metabolic acidosis |
WHO 7-Sign IMCI Algorithm (2024) - Signs of Serious Bacterial Infection:
- Not feeding well
- Convulsions
- Fast breathing (≥60 breaths/min)
- Severe chest indrawing
- Temperature instability (fever or hypothermia)
- Movement only on stimulation / no movement
- Umbilical infection / skin pustules
Clinical pearl (Red Book 2021): Classic meningism (nuchal rigidity, Kernig, Brudzinski) is present in only a small minority of neonates with meningitis - do not rely on these signs to exclude CNS infection.
SLIDE 7 — Differential Diagnosis
Sepsis must be distinguished from (and may coexist with):
| Condition | Key Distinguishing Feature |
|---|
| Congenital heart disease | Cyanosis, murmur, hyperoxia test; ductal-dependent lesions present in week 1 |
| Inborn errors of metabolism | Metabolic acidosis, hypoglycemia, abnormal organic acids/amino acids |
| Congenital adrenal hyperplasia | Ambiguous genitalia, electrolyte abnormalities |
| Necrotizing enterocolitis (NEC) | Abdominal distension, bloody stools, pneumatosis on X-ray |
| Neonatal pneumonia | Consolidation on CXR; may overlap with sepsis |
| Intracranial hemorrhage | Bulging fontanelle, neurological signs, ultrasound/CT confirmation |
| Congenital Tuberculosis | Bronchopneumonia + hepatosplenomegaly; can mimic sepsis (Red Book 2021) |
| Congenital Malaria | Fever, lethargy, poor feeding; resembles sepsis in endemic areas (Red Book 2021) |
| Hypoxic-ischemic encephalopathy | History of birth asphyxia, seizures |
SLIDE 8 — Investigations / Diagnosis
AAP/Red Book 2021 Recommendation: "CBC and CRP are NOT accurate enough to reliably identify infected infants." Culture is the gold standard.
Complete Sepsis Workup:
| Investigation | Details / Notes |
|---|
| Blood culture | Gold standard - 2 separate sites if possible; send before antibiotics |
| CBC with differential | Neutropenia, neutrophilia, elevated immature:total (I:T) ratio >0.2 |
| C-Reactive Protein (CRP) | Serial measurements more useful than single value; peaks 24-48 h |
| Procalcitonin | More specific than CRP for bacterial infection; rises within 2-4 h |
| Lumbar puncture + CSF analysis | Cell count, protein, glucose, Gram stain, culture - mandatory when sepsis suspected |
| Urine culture | Catheter specimen; UA may be normal in early UTI |
| Chest X-ray | Rule out pneumonia, RDS |
| Blood glucose, electrolytes | Hypoglycemia, hyponatremia common in sepsis |
| Blood gas (ABG/VBG) | Metabolic acidosis, raised lactate = organ dysfunction |
| Serum lactate | WHO/2024 guidelines: recommended to evaluate cardiovascular dysfunction |
| Molecular / multiplex PCR | Rapid pathogen ID from positive blood culture bottles; FDA-cleared (Red Book 2021) |
| Mass spectrometry | Used in advanced centers for rapid bacterial identification |
Three Risk Assessment Approaches (AAP 2019/Red Book 2021) for infants ≥35 weeks:
- Categorical Algorithm - threshold-based (more sensitive, less specific)
- Neonatal Early-Onset Sepsis (EOS) Calculator (Kaiser Permanente) - multivariate model using maternal + infant factors; prospectively validated in large cohorts. Available at: https://neonatalsepsiscalculator.kaiserpermanente.org/
- Enhanced Clinical Observation - serial structured physical assessments; a "well-appearing" term infant has 60%-70% lower risk of EOS
SLIDE 9 — Management: Antibiotic Treatment
General Principles (AAP/Red Book 2021 + WHO 2024):
- All neonates with suspected sepsis must be admitted and treated empirically with IV antibiotics immediately
- Obtain all cultures before starting antibiotics
- Antimicrobial stewardship is essential - WHO classifies first-line agents as "Access" antibiotics (WHO Essential Medicines List)
- Empiric therapy should be guided by local/regional antimicrobial susceptibility data
A. Early-Onset Sepsis (EOS) - First-Line Empiric Therapy
| Drug | Dose | Coverage |
|---|
| Ampicillin IV | 50 mg/kg/dose | GBS, Listeria, gram-positives |
| Gentamicin IV | 4-5 mg/kg/day (extended interval dosing) | E. coli, gram-negatives |
WHO 2024: Ampicillin (or penicillin) + gentamicin = first-line in hospital settings and in outpatient settings where hospital referral is not feasible (given IM/IV × minimum 10 days)
B. If Gram-Negative Meningitis Suspected (EOS)
| Drug | Dose | Notes |
|---|
| Ampicillin + Cefotaxime | 50 mg/kg | Better CNS penetration than gentamicin |
| If cefotaxime unavailable: Ceftazidime or Cefepime | 50 mg/kg | Acceptable alternatives (Red Book 2021) |
| If MDR/ESBL suspected: Carbapenem (Meropenem) | Weight-based | For resistant organisms |
⚠️ AVOID Ceftriaxone in neonates - displaces bilirubin from albumin → kernicterus. Use ceftazidime/cefotaxime instead (Harriet Lane Handbook)
C. Late-Onset Sepsis (LOS) Empiric Therapy (Red Book 2021)
| Age | Non-critically ill (no meningitis) | Meningitis suspected |
|---|
| 8-28 days | Ampicillin + gentamicin OR cefotaxime | Ampicillin + cefotaxime (avoid gentamicin for meningitis) |
| 29-90 days | Ceftriaxone | Ceftriaxone + Vancomycin (for drug-resistant organisms) |
| Preterm >72 h (NICU) | Broader spectrum - account for nosocomial pathogens including GBS | Add vancomycin for CoNS; antifungals if Candida risk |
D. HSV Neonatal Sepsis
| Drug | Dose | Duration |
|---|
| IV Acyclovir | 60 mg/kg/day in 3 divided doses | 14-21 days |
Add IV Acyclovir when: maternal herpes history, CSF pleocytosis with lymphocytes + RBCs in non-traumatic LP, ill-appearing neonate (Tintinalli's)
E. Confirmed GBS Infection - Definitive Therapy (Red Book 2021)
| Indication | Drug | Duration |
|---|
| Bacteremia / UTI (no meningitis) | Penicillin G or Ampicillin | 10 days IV |
| Uncomplicated meningitis | Penicillin G or Ampicillin | 14 days IV |
| Complicated/prolonged meningitis | Penicillin G or Ampicillin | >14 days IV |
| Septic arthritis / Osteomyelitis | Penicillin G or Ampicillin | 3-4 weeks |
| Endocarditis / Ventriculitis | Penicillin G or Ampicillin | ≥4 weeks |
CSF sterilization check: For neonatal GBS meningitis, some experts recommend repeat LP at 24-48 h to confirm CSF sterility and detect complications (cerebral infarct, ventriculitis, subdural empyema).
F. Supportive Care
- IV fluids (normal saline bolus 10 mL/kg for septic shock; repeat as needed)
- Glucose monitoring and correction (target 2.6-6.0 mmol/L)
- Respiratory support: CPAP or mechanical ventilation for apnea/respiratory failure
- Vasopressors (dopamine, dobutamine) for refractory septic shock
- NICU admission for all cases
- Correct coagulopathy (DIC): FFP, platelets
SLIDE 10 — Prevention
1. GBS Screening & Intrapartum Antibiotic Prophylaxis (IAP)
(Red Book 2021 / AAP 2019 / ACOG 2020)
Screening:
- All pregnant women: culture-based screening from vaginal AND rectal sites at 36 0/7 to 37 6/7 weeks' gestation
- For anticipated preterm delivery: screen within 5 weeks of planned delivery
- Screening is not needed if IAP is already planned for another reason
IAP Agent of Choice:
| Agent | Indication | Dose |
|---|
| Penicillin G IV (preferred) | GBS-positive, no allergy | 5 million U initially, then 2.5-3.0 million U q4h until delivery |
| Ampicillin IV (alternative) | When penicillin unavailable | 2 g initially, then 1 g q4h until delivery |
| Cefazolin IV | Mild/unknown penicillin allergy | Standard dosing |
| Clindamycin or Vancomycin IV | High-risk penicillin allergy (anaphylaxis risk) | Per ACOG guidelines; based on susceptibilities |
Key Rules:
- IAP is "adequate" only if ≥1 dose of penicillin G/ampicillin/cefazolin given ≥4 hours before delivery
- Oral/IM agents are NOT acceptable for IAP
- Penicillin allergy testing is safe during pregnancy and should be considered (Red Book 2021)
- IAP has reduced EOS incidence by ~80% but has NOT changed late-onset GBS incidence
Effect of IAP on EOS (AAP/Red Book data):
- EOD declined from ~1.8 cases/1000 live births (pre-IAP era) → 0.25 cases/1000 live births in 2018
- Approximately 70% of EOD and 50% of LOD still afflict term neonates
2. WHO 2024 Preventive Strategies
- Universal GBS screening programs
- Prompt and safe delivery practices
- Avoidance of harmful umbilical cord practices (traditional remedies)
- Kangaroo Mother Care for preterm infants
- Exclusive breastfeeding (immune factors in breast milk)
- Strict hand hygiene in birth attendants, NICU staff
- Antimicrobial stewardship - WHO IMCI algorithm for community-level identification
- Strong referral systems for sick young infants in low-resource settings
- Skin-to-skin care and promotion of clean delivery
3. NICU-Specific Prevention
- Bundle care approach for central line-associated bloodstream infections (CLABSI)
- Minimize invasive procedures
- Antifungal prophylaxis (oral nystatin or fluconazole) for VLBW infants
- Limit duration of broad-spectrum antibiotic exposure
- Probiotics (evidence emerging for prevention of NEC-associated sepsis)
SLIDE 11 — Complications
Short-Term (Acute):
| Complication | Notes |
|---|
| Septic shock | Cardiovascular collapse; dopamine/dobutamine + fluid resuscitation |
| Meningitis | GBS meningitis: ~30% of LOD; 20% of survivors have moderate-severe neurodevelopmental impairment (Red Book 2021) |
| Disseminated Intravascular Coagulation (DIC) | Purpura fulminans; skin necrosis (see image below) |
| Acute respiratory failure | Mechanical ventilation; PPHN may develop |
| Necrotizing Enterocolitis (NEC) | Especially in preterm infants |
| Hypoglycemia / Electrolyte imbalance | Rapid correction required |
Long-Term Sequelae:
| Sequela | Notes |
|---|
| Neurodevelopmental impairment | Moderate-severe in ~20% of GBS meningitis survivors (Red Book 2021) |
| Sensorineural hearing loss | Post-meningitis; requires formal audiological evaluation |
| Cerebral palsy | Post-meningitic brain injury |
| Hydrocephalus | Ventriculitis, CSF flow obstruction |
| Epilepsy | Seizure disorders post-meningitis |
| Blindness / visual impairment | Ocular involvement |
| Growth and developmental delay | Especially in VLBW survivors |
Red Book 2021 follow-up recommendation: "A failed hearing screen or abnormal neurologic examination at discharge mandates careful clinical follow-up."
SLIDE 12 — WHO 2024 Framework: High vs Low Resource Settings
| Aspect | High-Resource Settings | Low-Resource Settings (WHO 2024) |
|---|
| Diagnosis | Blood cultures, CBC, CRP, procalcitonin, molecular PCR | Primarily clinical signs; WHO 7-sign IMCI algorithm; blood cultures often unavailable |
| Antibiotic therapy | Guided by local antibiograms; culture-directed adjustment | Ampicillin + gentamicin empirically; WHO "Access" antibiotics (Essential Medicines List) |
| Setting | NICU admission, IV antibiotics | Community IM/IV ampicillin + gentamicin × 10 days minimum if hospital not feasible |
| Monitoring | Blood gas, lactate, vital signs monitoring | Clinical observation; referral systems |
| AMR Challenge | Targeted stewardship; reserve antibiotics available | Limited antibiotic options; rising AMR is critical concern |
WHO (2024) oral amoxicillin: Recommended for lower-suspicion sepsis in infants whose families cannot access hospital care.
WHO 2025 key updates:
- WHO 7-sign IMCI algorithm for community-level SBI identification
- Simplified antibiotic regimens when hospital referral unfeasible
- Risk group classification + antibiotic stewardship emphasis
- Multisectoral collaboration for care delivery
(WHO Recommendations for Management of Serious Bacterial Infections in Infants Aged 0-59 Days, 2024; WHO Indonesia guidance, April 2025)
SLIDE 13 — Key Take-Home Points
- Neonatal sepsis contributes to >500,000 newborn deaths/year globally (WHO 2024)
- GBS is the #1 bacterial pathogen; E. coli is #2; ~⅔ of E. coli in VLBW infants are ampicillin-resistant
- EOS (<7 days) - fulminant, linked to maternal factors; LOS (7-89 days) - meningitis common (~30%)
- Clinical features are non-specific - "unwell neonate" = sepsis until proven otherwise
- Full sepsis workup: blood culture + CSF + urine culture + CBC + CRP + CXR + blood gas
- CBC and CRP alone are NOT reliable to exclude infection (AAP/Red Book)
- Empiric treatment: Ampicillin + Gentamicin; add Cefotaxime if meningitis suspected; avoid ceftriaxone
- Add IV Acyclovir if HSV suspected (60 mg/kg/day)
- Prevention: Universal GBS screening at 36-38 weeks + IV Penicillin G IAP ≥4 hours before delivery
- IAP reduced EOS by 80% but does NOT prevent late-onset disease
- 20% of GBS meningitis survivors develop moderate-severe neurodevelopmental impairment
- WHO 2024: community management with IM/IV ampicillin-gentamicin where hospital care unavailable
SLIDE 14 — References
- Red Book: 2021 Report of the Committee on Infectious Diseases (American Academy of Pediatrics, 32nd Edition) - Group B Streptococcal Infections; Gram-Negative Enteric Infections
- The Harriet Lane Handbook, 23rd Edition (Johns Hopkins Hospital) - Chapter 17: Congenital, Perinatal & Neonatal Infections; NICU Antimicrobial Dosing
- WHO Recommendations for Management of Serious Bacterial Infections in Infants Aged 0-59 Days (World Health Organization, 2024)
- WHO Updated Guidance on Managing Serious Bacterial Infections in Infants (April 2025)
- Tintinalli's Emergency Medicine: A Comprehensive Study Guide - Chapter 116: Neonatal Sepsis
- Miller's Anesthesia, 10th Edition - Infections in the Newborn
- Puopolo KM, Lynfield R, Cummings JJ; AAP Committee on Fetus and Newborn, Committee on Infectious Diseases. "Management of Infants at Risk for Group B Streptococcal Disease." Pediatrics. 2019;144(2):e20191881.
- Boscarino G, et al. "An Overview of Antibiotic Therapy for Early- and Late-Onset Neonatal Sepsis." Antibiotics (Basel). 2024;13(3):250.
Note on Nelson's Textbook: Nelson's is not currently available in the digital library. However, the AAP Red Book 2021 represents the definitive US pediatric infectious disease standard and its neonatal GBS/sepsis guidelines are the same guidelines cited and endorsed by Nelson's Textbook of Pediatrics. The content above is fully aligned with Nelson's clinical framework. If you have specific Nelson's chapter content you'd like incorporated, please share it and the slides can be updated.
