Overview
Definition:
Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of systemic infection in the first 28 days of life
It is a medical emergency with high morbidity and mortality
Early and accurate evaluation is critical for timely intervention.
Epidemiology:
The incidence of neonatal sepsis varies globally, ranging from 1 to 8 cases per 1,000 live births
Prematurity, low birth weight, prolonged rupture of membranes, maternal chorioamnionitis, and invasive procedures are significant risk factors
Early-onset sepsis (EOS) typically occurs within 72 hours of birth, while late-onset sepsis (LOS) occurs after 72 hours and up to 28 days.
Clinical Significance:
Neonatal sepsis is a leading cause of preventable infant mortality
Prompt recognition and management can significantly improve outcomes, reducing mortality and long-term sequelae such as neurological impairment, hearing loss, and developmental delays
This topic is a cornerstone of pediatric residency training and crucial for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Non-specific symptoms are common
These may include lethargy or irritability
Difficulty in feeding or poor suck
Vomiting
Diarrhea or constipation
Changes in tone (hypotonia or hypertonia)
Tachypnea or apnea
Temperature instability (hypothermia or fever)
Jaundice
Seizures.
Signs:
Vital sign abnormalities: Tachycardia or bradycardia
Tachypnea or apnea
Hypotension
Temperature instability (most commonly hypothermia in newborns)
Physical examination findings: Pallor
Mottled skin
Petechiae or purpura
Umbilical cord inflammation or discharge
Hepatosplenomegaly
Signs of respiratory distress (grunting, retractions, nasal flaring)
Signs of poor perfusion (delayed capillary refill, cool extremities).
Diagnostic Criteria:
There are no definitive diagnostic criteria for neonatal sepsis
diagnosis is based on a combination of clinical suspicion, laboratory findings, and microbiological confirmation
The presence of two or more clinical signs of systemic inflammation in a neonate with a suspected or proven infection is highly suggestive
Blood culture remains the gold standard for microbiological confirmation, though it can take 24-72 hours for results.
Diagnostic Approach
History Taking:
Key history points include maternal history of GBS colonization, urinary tract infections, prolonged rupture of membranes (>18 hours), fever during labor, and pre-term labor
Neonatal history should focus on gestational age, birth weight, signs of distress at birth, any procedures performed (e.g., intubation, line insertion), and duration of symptoms
Red flags include maternal fever, foul-smelling amniotic fluid, and unexplained deterioration in the neonate.
Physical Examination:
A thorough and systematic physical examination is essential
This includes a complete assessment of vital signs, skin for rashes or petechiae, respiratory status, cardiovascular system, abdominal distension or tenderness, neurological assessment for tone and reflexes, and examination of the umbilical cord and any invasive lines
A detailed examination helps identify potential sources of infection.
Investigations:
Essential investigations include: Complete Blood Count (CBC) with differential: Leukocytosis or leukopenia, elevated immature-to-total neutrophil ratio (>0.2), and thrombocytopenia are suggestive
C-Reactive Protein (CRP): Rises within hours of infection and is a useful marker of inflammation, though it can have a delayed rise
Procalcitonin: More specific marker for bacterial infection than CRP
Blood culture: Essential for identifying the causative organism and guiding antibiotic therapy
Urine culture: Useful for diagnosing urinary tract infections, especially in late-onset sepsis
Lumbar puncture: To rule out meningitis
cerebrospinal fluid (CSF) analysis includes cell count, protein, glucose, and Gram stain/culture
Chest X-ray: If respiratory symptoms are present, to rule out pneumonia
Other investigations may include: Viral serology, PCR for specific pathogens, ultrasound of the abdomen or head if indicated.
Differential Diagnosis:
Conditions that can mimic neonatal sepsis include: Hypoxic-ischemic encephalopathy (HIE)
Congenital anomalies (e.g., congenital heart disease, gastrointestinal malformations)
Metabolic disorders (e.g., hypoglycemia, inborn errors of metabolism)
Neonatal abstinence syndrome
Transient tachypnea of the newborn (TTN)
Early presentation of non-infectious conditions like anemia or hyperbilirubinemia.
Management
Initial Management:
Initial management is directed at stabilization and empiric treatment
This includes ensuring adequate airway, breathing, and circulation (ABCs)
If hypotension is present, fluid resuscitation with normal saline (10-20 mL/kg) is crucial
Antibiotic therapy should be initiated empirically as soon as blood cultures are drawn
Common empirical regimens include ampicillin and gentamicin, or ampicillin and a third-generation cephalosporin, depending on local resistance patterns and suspected organisms.
Medical Management:
Empirical antibiotic therapy is initiated based on suspected pathogens and local antibiograms
For suspected early-onset sepsis (e.g., Group B Streptococcus, E
coli), ampicillin and gentamicin are commonly used
For late-onset sepsis, broader-spectrum agents like vancomycin (if MRSA suspected) and a third-generation cephalosporin (e.g., cefotaxime) or piperacillin-tazobactam may be considered
Antibiotic choice is adjusted based on culture and sensitivity results
Duration of therapy is typically 7-10 days for confirmed sepsis, and shorter courses may be considered for culture-negative presumed sepsis.
Surgical Management:
Surgical management is not typically indicated for primary sepsis but may be required if a specific focus of infection is identified that requires drainage or debridement
Examples include surgical intervention for necrotizing enterocolitis (NEC), osteomyelitis, or an abscess
Management of central venous lines that may be a source of infection might involve removal.
Supportive Care:
Comprehensive supportive care is vital
This includes meticulous fluid and electrolyte management, nutritional support (enteral or parenteral), thermoregulation, respiratory support (oxygen, CPAP, mechanical ventilation), and close monitoring of vital signs, urine output, and metabolic parameters
Neonatal intensive care unit (NICU) admission is usually necessary for close observation and management.
Complications
Early Complications:
Early complications include: Disseminated intravascular coagulation (DIC)
Acute kidney injury
Respiratory distress syndrome
Persistent pulmonary hypertension of the newborn (PPHN)
Shock
Seizures
Necrotizing enterocolitis (NEC).
Late Complications:
Late complications can significantly impact long-term outcomes: Neurological sequelae (cerebral palsy, developmental delay, cognitive impairment)
Sensory deficits (hearing or visual impairment)
Chronic lung disease
Growth restriction
Sepsis-related death.
Prevention Strategies:
Prevention strategies include: Antenatal care to identify and manage maternal infections
Prompt administration of intrapartum antibiotics for GBS-colonized mothers
Strict aseptic techniques during delivery and any invasive procedures
Judicious use of antibiotics to prevent resistance
Early recognition of risk factors and clinical signs.
Prognosis
Factors Affecting Prognosis:
Prognosis is influenced by: Gestational age and birth weight (premature and low birth weight infants have poorer outcomes)
Causative organism (e.g., Gram-negative bacteria and certain Gram-positive organisms like Staphylococcus aureus are associated with higher mortality)
Severity of illness at presentation
Timeliness and appropriateness of treatment
Development of complications like meningitis or NEC.
Outcomes:
Mortality rates for neonatal sepsis can range from 5-20% or higher, depending on the factors above
Survivors may experience significant long-term morbidity
Early-onset sepsis generally has a better prognosis than late-onset sepsis if treated promptly.
Follow Up:
Neonates who have had sepsis require close follow-up
This includes monitoring for neurodevelopmental outcomes, growth, and hearing/vision screening
Regular assessments by pediatricians and relevant specialists (e.g., developmental pediatricians, audiologists) are crucial to identify and manage any sequelae early.
Key Points
Exam Focus:
Recognize non-specific symptoms in neonates
Understand the importance of a comprehensive sepsis workup
Differentiate early-onset vs
late-onset sepsis
Know common empirical antibiotic regimens and their indications
Be aware of major complications and prognostic factors
Remember that blood cultures are the gold standard for diagnosis.
Clinical Pearls:
Always consider sepsis in any sick neonate, even with subtle signs
Draw blood cultures BEFORE starting antibiotics whenever possible
Early initiation of broad-spectrum antibiotics is life-saving
Lumbar puncture is crucial for suspected meningitis, even if CSF is initially clear
Monitor CRP and procalcitonin serially to assess response to treatment.
Common Mistakes:
Delaying antibiotic treatment until culture results are available
Inadequate fluid resuscitation in shock
Missing subtle signs of sepsis in premature infants
Not performing a lumbar puncture when clinically indicated
Prescribing antibiotics for too long or too short a duration without clear indications
Failing to follow up on neurodevelopmental outcomes in survivors.