Overview
Definition:
Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of systemic infection in the first 28 days of life
It can be classified based on the timing of onset: Early Onset Sepsis (EOS) occurring within the first 72 hours of life, and Late Onset Sepsis (LOS) occurring after 72 hours but before 28 days of life.
Epidemiology:
Incidence of neonatal sepsis varies globally, with higher rates in developing countries
EOS is typically caused by maternal pathogens transmitted vertically, while LOS is often acquired from the environment or hospital-acquired
Common pathogens include Group B Streptococcus (GBS), Escherichia coli, and other gram-negative bacilli.
Clinical Significance:
Neonatal sepsis is a leading cause of neonatal mortality and morbidity
Prompt recognition and management are crucial to improve outcomes
Differentiating between EOS and LOS is important as etiological agents, risk factors, and management strategies can differ, impacting prognosis and necessitating specific diagnostic and therapeutic algorithms.
Clinical Presentation
Symptoms:
Vague and nonspecific signs
Lethargy
Irritability
Poor feeding
Vomiting
Diarrhea
Jaundice
Apnea
Bradycardia or tachycardia
Hypotension
Temperature instability (hypothermia or fever)
Tachypnea
Grunting
Pallor or cyanosis
Seizures.
Signs:
Generalized edema
Petechiae or purpura
Abdominal distension
Hepatomegaly or splenomegaly
Poor capillary refill
Signs of shock
Clinical evidence of meningitis or pneumonia.
Diagnostic Criteria:
No single criterion
Diagnosis based on clinical suspicion combined with laboratory evidence
Common criteria include a history of suspected infection in a neonate with at least two clinical signs of infection AND elevated inflammatory markers (e.g., elevated WBC count, immature to total neutrophil ratio, elevated CRP, or positive blood culture)
Specific guidelines from organizations like the AAP and WHO should be followed.
Diagnostic Approach
History Taking:
Maternal history: prolonged rupture of membranes (>18 hours), maternal fever, chorioamnionitis, GBS colonization and prophylaxis status, urinary tract infection in pregnancy
Neonatal history: gestational age, mode of delivery, birth weight, presence of congenital anomalies, prior antibiotic exposure
History of fever, feeding intolerance, lethargy, or respiratory distress in the neonate.
Physical Examination:
Complete physical examination focusing on vital signs (temperature, heart rate, respiratory rate, blood pressure, oxygen saturation)
Assess for signs of respiratory distress, poor perfusion, neurological deficits, skin lesions (petechiae, jaundice, edema), and abdominal findings
A thorough systemic examination is essential to identify foci of infection.
Investigations:
Complete blood count (CBC) with differential (look for leukocytosis/leukopenia, increased I:T ratio)
Blood culture (essential for definitive diagnosis
ideally drawn before antibiotics)
C-reactive protein (CRP) or Procalcitonin (PCT) (markers of inflammation
serial monitoring useful)
Urine culture (especially for LOS)
Lumbar puncture for cerebrospinal fluid (CSF) analysis and culture (if meningitis suspected)
Chest X-ray (if pneumonia suspected)
Sepsis screen (e.g., urine analysis, blood count, blood culture).
Differential Diagnosis:
Non-infectious causes of similar symptoms: hypoxic-ischemic encephalopathy, congenital heart disease, metabolic disorders, surgical conditions (e.g., necrotizing enterocolitis, intestinal obstruction), drug withdrawal, respiratory distress syndrome, transient tachypnea of the newborn, hyperbilirubinemia.
Management Eos
Initial Management:
Immediate resuscitation and stabilization
Ensure adequate airway, breathing, and circulation
Establish intravenous access for fluids and medications
Administer oxygen as needed
Monitor vital signs continuously
Blood glucose monitoring.
Medical Management:
Empirical broad-spectrum antibiotic therapy should be initiated as soon as sepsis is suspected and blood cultures have been obtained
For EOS, common regimens include Ampicillin plus a third-generation cephalosporin (e.g., Gentamicin or Cefotaxime)
Duration of therapy is typically 7-10 days for culture-proven sepsis, or 48-72 hours if cultures are negative and clinical suspicion is low.
Supportive Care:
Maintain fluid and electrolyte balance
Nutritional support (enteral or parenteral)
Management of hypotension with intravenous fluids and inotropes if necessary
Mechanical ventilation if respiratory failure occurs
Monitor for complications like DIC, hypoglycemia, and seizures.
Management Los
Initial Management:
Similar to EOS: stabilization, IV access, oxygen support, and continuous monitoring
Prompt assessment for potential sources of infection (e.g., indwelling catheters, central lines).
Medical Management:
Antibiotic selection for LOS depends on local epidemiology, suspected source of infection, and prior antibiotic exposure
Commonly used regimens include Vancomycin (if MRSA is suspected or confirmed, or for CNS involvement) in combination with a broader-spectrum agent like Piperacillin-Tazobactam or Meropenem
Adjust therapy based on culture and sensitivity results
Duration is typically 10-14 days or longer depending on the pathogen and site of infection.
Supportive Care:
Aggressive fluid management, vasopressor support if hemodynamically unstable, respiratory support (including mechanical ventilation), management of coagulopathy (DIC), and metabolic disturbances
Careful monitoring for complications such as organ dysfunction, surgical intervention for complications like NEC, and prolonged hospitalization.
Key Points
Exam Focus:
Differentiate EOS from LOS based on timing and common pathogens
Understand the risk factors for each
Recall empirical antibiotic choices for EOS and LOS, including specific drug classes and common agents
Know the importance of blood cultures before antibiotics and subsequent antibiotic adjustment based on sensitivities
Recognize that nonspecific signs are common in neonates.
Clinical Pearls:
Always obtain blood cultures before administering antibiotics for suspected sepsis
Consider a sepsis screen for any neonate with concerning symptoms
Serial CRP or PCT can help monitor response to treatment
Lumbar puncture is mandatory if meningitis is suspected, even in the presence of hypotension or coagulopathy
Follow established guidelines for antibiotic duration.
Common Mistakes:
Delaying antibiotic administration
Forgetting to draw blood cultures before starting antibiotics
Inadequate fluid resuscitation in hypotensive neonates
Not considering CNS involvement and omitting LP when indicated
Treating solely based on inflammatory markers without clinical suspicion or positive cultures
Using narrow-spectrum antibiotics too early without considering resistant organisms.