What is the recommended antibiotics policy for suspected or proven sepsis in the Neonatal Intensive Care Unit (NICU)?

Recommended Antibiotics Policy for Suspected or Proven Sepsis in NICU

For suspected or proven sepsis in the NICU, the first-line empiric antibiotic therapy should be a combination of ampicillin (50 mg/kg IV every 6 hours) plus gentamicin (5-7.5 mg/kg IV daily), with prompt de-escalation or discontinuation after 48 hours if cultures remain negative and clinical suspicion is low. 1

First-Line Antibiotic Regimens

Early-Onset Sepsis (first 72 hours of life)

• First choice: Ampicillin + gentamicin 2, 1
  • Ampicillin: 50 mg/kg IV every 6 hours
  • Gentamicin: 5-7.5 mg/kg IV once daily

Late-Onset Sepsis (>72 hours to 1 month)

• First choice: Ampicillin + gentamicin 2, 1
• Alternative if staphylococcal infection suspected: Flucloxacillin + gentamicin 1

Second-Line Antibiotic Options

• Amikacin + cloxacillin 2
• Cefotaxime (when gram-negative resistance is suspected) 2, 1
• Ceftriaxone (except in neonates with hyperbilirubinemia) 2

Rationale for First-Line Selection

1. The combination of ampicillin and gentamicin effectively covers the most common pathogens in neonatal sepsis:

   • Group B Streptococcus (covered by ampicillin)
   • Escherichia coli and other gram-negative bacteria (covered by gentamicin) 1

2. This combination is associated with less emergence of resistant bacteria compared to regimens using broad-spectrum cephalosporins 1

3. Multiple guidelines consistently recommend this combination, including the American Academy of Pediatrics, WHO, and UK NICE guidelines 2, 1

Dosing Considerations for Gentamicin

• Once-daily dosing of gentamicin is superior to multiple doses per day based on pharmacokinetic properties 3
• Once-daily dosing achieves higher peak levels while avoiding toxic trough levels 3
• For neonates, 5-7.5 mg/kg IV once daily is recommended, with dosing adjusted based on gestational and postnatal age 1, 4
• Monitor trough levels before the third dose to ensure they are <2 μg/mL 3

When to Consider Alternative or Broader Coverage

1. Add cefotaxime when:

   • Evidence of gram-negative bacterial sepsis 2
   • Confirmed meningitis 1
   • Documented aminoglycoside resistance 1

2. Consider broader coverage for hospital-acquired sepsis with:

   • High risk for resistant organisms
   • Prior antibiotic exposure
   • Local antibiogram showing high resistance patterns 1

Duration of Therapy

• Culture-negative sepsis: 7-10 days 1
• Culture-positive sepsis: 10-14 days 1
• Bacterial meningitis: 14-21 days 1
• Minimum duration: Continue antibiotics for at least 48-72 hours after patient defervesces 5

Antibiotic Stewardship Principles

1. Daily reassessment: Consider de-escalation or discontinuation after 48 hours if:

   • Blood cultures remain negative
   • Clinical signs of infection resolve
   • Alternative diagnosis is established 1

2. Avoid prolonged empiric therapy without evidence of infection to prevent:

   • Emergence of resistant organisms
   • Adverse drug events
   • Disruption of normal microbiome 1

3. Obtain blood cultures before initiating antibiotics when this does not substantially delay administration 1

Common Pitfalls to Avoid

1. Routine use of third-generation cephalosporins as first-line therapy promotes antimicrobial resistance 1

2. Failure to adjust dosing for renal function, particularly in premature neonates with decreased renal clearance 1

3. Not considering local resistance patterns when selecting empiric therapy 2, 1

4. Continuing broad-spectrum antibiotics unnecessarily beyond 48 hours when probability of sepsis is low 1

5. Inadequate gentamicin dosing leading to treatment failure, particularly for pathogens with higher MICs 6

By following this evidence-based approach to antibiotic selection in the NICU, clinicians can effectively treat neonatal sepsis while minimizing the risks of antimicrobial resistance and adverse effects.