What is the role of amoxicillin (amoxicillin) and sulbactam in preterm premature rupture of membranes (PPROM)?

Role of Amoxicillin and Sulbactam in Preterm Premature Rupture of Membranes (PPROM)

Amoxicillin is recommended as part of the standard antibiotic regimen for PPROM at ≥24 weeks gestation, but sulbactam (as part of amoxicillin-clavulanic acid) should be avoided due to increased risk of necrotizing enterocolitis in neonates. 1

Recommended Antibiotic Regimens for PPROM

Based on Gestational Age:

• ≥24 weeks gestation (strong recommendation, GRADE 1B):

  • 7-day course of antibiotic therapy consisting of: 1
    • IV ampicillin and erythromycin for 48 hours, followed by
    • Oral amoxicillin and erythromycin for additional 5 days

• 20 0/7 to 23 6/7 weeks gestation (conditional recommendation, GRADE 2C):

  • Antibiotics can be considered but have less supporting evidence 1
  • When used, follow the same regimen as for ≥24 weeks

• <20 weeks gestation:

  • Limited evidence of benefit 1
  • Shared decision-making recommended regarding potential benefits and risks

Specific Antibiotic Choices and Considerations

• Recommended regimen (based on largest randomized controlled trials): 1, 2

  • Ampicillin 2g IV every 6 hours AND erythromycin 250mg IV every 6 hours for 48 hours
  • FOLLOWED BY amoxicillin 250mg orally every 8 hours AND erythromycin 333mg orally every 8 hours for 5 days

• Alternative regimen: 2

  • Erythromycin 250mg orally every 6 hours for 10 days

• Important cautions:

  • Amoxicillin-clavulanic acid (sulbactam) should NOT be used due to increased risk of necrotizing enterocolitis in neonates 1, 2
  • Amoxicillin without clavulanic acid is safe 2
  • Azithromycin can substitute for erythromycin when erythromycin is unavailable 1, 3

Benefits of Appropriate Antibiotic Therapy

• Prolongs pregnancy latency 1, 4, 5
• Reduces maternal infection and chorioamnionitis 2, 5
• Decreases neonatal morbidity 1, 4, 6
• Associated with improved neonatal survival without severe morbidity 5, 7

Emerging Evidence

• Recent research suggests third-generation cephalosporins may be associated with improved survival without severe neonatal morbidity compared to amoxicillin in PPROM at 24-31 weeks (adjusted risk ratio 1.25 [95% CI 1.08-1.45]) 7
• However, current guidelines still recommend the ampicillin/amoxicillin and erythromycin regimen based on the largest randomized controlled trials 1, 2

Clinical Pitfalls to Avoid

• Using amoxicillin-clavulanic acid (sulbactam) combination due to increased necrotizing enterocolitis risk 1, 2
• Delaying antibiotic administration in patients ≥24 weeks gestation 3
• Prolonged or repeated antibiotic courses beyond what would be used for PPROM at later gestational ages 1
• Failing to screen for and treat urinary tract infections, sexually transmitted infections, and group B streptococcus carriage 2

Timing of Antibiotic Administration

• A retrospective cohort study of PPROM at 16-23 6/7 weeks showed no significant difference in outcomes between immediate (<24 hours) versus delayed (>24 hours) antibiotic administration 1
• However, prompt administration is still recommended when indicated based on gestational age 3