What is the recommended management for presumed sepsis in neonates?

Management of Presumed Sepsis in Neonates

For neonates with presumed sepsis, the first-line empirical antibiotic therapy should be ampicillin plus gentamicin, which provides optimal coverage against the most common pathogens while minimizing risks of antimicrobial resistance and mortality. 1, 2

Classification and Initial Assessment

• Neonatal sepsis is classified as early-onset (≤72 hours of life) or late-onset (>72 hours to 28 days), which guides empiric antibiotic selection 1
• All newborns with signs suggestive of sepsis require immediate blood culture collection followed by prompt initiation of empirical antibiotics without waiting for results 1, 3
• For well-appearing newborns born to mothers with chorioamnionitis, a "limited evaluation" including complete blood count with differential and blood culture is recommended before starting antibiotics 1

First-Line Empirical Antibiotic Therapy

• Early-onset sepsis (≤72 hours):

  • Ampicillin plus gentamicin is the recommended first-line regimen 1, 3, 2
  • This combination provides coverage against Group B Streptococcus, Enterobacteriaceae (especially E. coli), and Listeria monocytogenes 1, 4, 5
  • Benzylpenicillin (penicillin G) may be substituted for ampicillin with equivalent efficacy 1, 6

• Late-onset sepsis (>72 hours to 28 days):

  • Ampicillin plus gentamicin remains appropriate initial therapy 2, 5
  • Consider adding vancomycin if coagulase-negative staphylococci are suspected, particularly in hospitalized or NICU patients 1, 3, 7

Second-Line and Alternative Regimens

• If gram-negative sepsis is suspected or confirmed, cefotaxime may replace gentamicin 1, 3, 8
• For hospital-acquired infections, amikacin plus cloxacillin is recommended when resistant staphylococcal infection is a concern 3, 2
• Third-generation cephalosporins should not be used routinely as first-line therapy due to risk of rapidly emerging resistance 5, 7

Duration of Therapy and Monitoring

• For culture-negative suspected sepsis in well-appearing infants, antibiotics can be discontinued after 48-72 hours if cultures remain negative 5, 7
• For confirmed sepsis, treat for 10-14 days in most cases 5
• Monitor complete blood count with differential and platelet counts during treatment 2
• Reassess antibiotic therapy when culture and susceptibility results become available 4, 5

Special Considerations

• In regions with high antimicrobial resistance, particularly in low and middle-income countries, local resistance patterns should guide empiric therapy 1, 9
• Recent studies show concerning levels of resistance to ampicillin (76.6%) and gentamicin (8.5%) among gram-negative isolates, with 7.3% resistant to both 10
• Despite resistance concerns, the combination of ampicillin and gentamicin remains effective against the vast majority of contemporary early-onset sepsis pathogens 10

Common Pitfalls to Avoid

• Delaying antibiotic initiation while awaiting culture results increases mortality risk 3, 2
• Continuing antibiotics beyond 48-72 hours in well-appearing infants with negative cultures contributes to antimicrobial resistance 5
• Using third-generation cephalosporins as routine first-line therapy has been associated with increased mortality and emergence of resistant organisms 5, 7
• Failing to adjust therapy based on culture results and clinical response 4, 5