What are the causes of neonatal sepsis?

Causes of Neonatal Sepsis

Gram-negative bacteria are the predominant cause of neonatal sepsis worldwide, accounting for approximately 60% of cases, with significant regional variations in pathogen distribution and concerning levels of antimicrobial resistance. 1

Classification of Neonatal Sepsis

Neonatal sepsis is typically classified based on timing of onset:

• Early-onset sepsis (EOS):

  • Occurs within 72 hours to 7 days of birth (definitions vary)
  • Traditionally associated with organisms acquired peripartum from maternal genital tract
  • Major pathogens: Group B Streptococcus, enteric Gram-negative bacteria (especially E. coli)

• Late-onset sepsis (LOS):

  • Occurs after 72 hours or 7 days up to 28 days of life
  • Often associated with hospital-acquired pathogens
  • Risk factors include very low birth weight and early gestational age

Major Causative Organisms

Gram-negative Bacteria (60% of cases in low and lower-middle-income countries)

1. Klebsiella species (38% of Gram-negative sepsis)

   • More common in Africa (44%) than Asia (35%)

2. Escherichia coli (15% of Gram-negative sepsis)

   • Second most common bacterial cause of neonatal sepsis overall

3. Pseudomonas species (7% of Gram-negative sepsis)

4. Acinetobacter species (6% of Gram-negative sepsis)

   • More common in Asia (10%) than Africa (3%)

5. Enterobacter species (3% of Gram-negative sepsis)

Gram-positive Bacteria

1. Staphylococcus species

   • Coagulase-positive (S. aureus)
   • Coagulase-negative staphylococci (predominant in late-onset sepsis) 2

2. Group B Streptococcus

   • Major cause of early-onset sepsis in developed countries 1

3. Enterococci

4. Listeria monocytogenes 3

Regional Variations in Pathogen Distribution

• Africa: Higher prevalence of Klebsiella species (44%) and higher rates of third-generation cephalosporin resistance
• Asia: Higher prevalence of Acinetobacter species (10%) and higher rates of ciprofloxacin resistance

Antimicrobial Resistance Patterns

Significant resistance to WHO-recommended first-line antimicrobials has been documented:

• Ampicillin resistance: 90% in E. coli
• Gentamicin resistance: 42-70% across Gram-negative species
• Third-generation cephalosporin resistance: 57-81% in most Gram-negative species
• Carbapenem resistance: 10% in E. coli and Klebsiella, 42% in Acinetobacter

Risk Factors for Neonatal Sepsis

Maternal Risk Factors

• Maternal GBS colonization
• Prolonged rupture of membranes (>18 hours)
• Maternal fever or chorioamnionitis
• Urinary tract infection during pregnancy (GBS bacteriuria is a marker for heavy genital tract colonization) 1

Neonatal Risk Factors

• Prematurity
• Low birth weight
• Male gender
• Invasive procedures
• Prolonged hospital stay
• Central venous catheters

Clinical Implications

1. Empiric Antibiotic Selection:

   • Traditional first-line therapy (ampicillin/penicillin plus gentamicin) may be inadequate in many settings due to high resistance rates 1
   • Gentamicin is indicated for serious infections caused by susceptible strains of Pseudomonas, Proteus, E. coli, Klebsiella, Enterobacter, Serratia, Citrobacter, and Staphylococcus species 4
   • Regional antimicrobial resistance patterns should guide empiric therapy

2. Diagnostic Challenges:

   • Blood cultures remain the gold standard but have limitations
   • Initial signs of neonatal sepsis are often subtle and nonspecific

3. Antibiotic Stewardship:

   • Prolonged empiric antibiotic therapy is associated with adverse outcomes and increased antimicrobial resistance
   • Reevaluation of antibiotic therapy when culture results are available is essential

Prevention Strategies

• Intrapartum antibiotic prophylaxis for GBS-positive mothers
• Strict infection control measures in neonatal units
• Appropriate hand hygiene
• Minimizing invasive procedures
• Antimicrobial stewardship programs

Conclusion

The epidemiology of neonatal sepsis shows concerning trends with Gram-negative predominance and high levels of antimicrobial resistance, particularly in low and middle-income countries. Regional surveillance of pathogens and their resistance patterns is essential to guide appropriate empiric therapy and improve outcomes in this vulnerable population.