What is the recommended antibiotic regimen for women with premature rupture of membranes (PROM)?

Antibiotic Regimen for Premature Rupture of Membranes (PROM)

For women with preterm premature rupture of membranes (PPROM), the recommended antibiotic regimen is ampicillin 2g IV every 6 hours and erythromycin 250mg IV every 6 hours for 48 hours, followed by oral amoxicillin 250mg every 8 hours and erythromycin 333mg every 8 hours for 5 days. 1

Antibiotic Recommendations Based on Gestational Age

For PPROM at <34 weeks:

• Antibiotics should be administered to women who are not in labor to prolong pregnancy and decrease maternal and neonatal morbidity 1
• The recommended 7-day course consists of:
  • Initial 48 hours: Ampicillin 2g IV every 6 hours AND erythromycin 250mg IV every 6 hours 1, 2
  • Followed by 5 days: Oral amoxicillin 250mg every 8 hours AND erythromycin 333mg every 8 hours 1, 2
• Alternative regimen: Erythromycin 250mg orally every 6 hours for 10 days 1

For PPROM at 20-23 6/7 weeks:

• Antibiotics can be considered to prolong latency and reduce neonatal morbidity 3
• The same regimen as above is recommended based on clinical evidence 3

For PPROM at ≥24 weeks:

• Antibiotics are strongly recommended for expectant management 3

Special Considerations for Group B Streptococcus (GBS)

For women with PPROM and unknown GBS status:

• Obtain vaginal-rectal swab for GBS culture and start antibiotics for latency or GBS prophylaxis 3
• If receiving antibiotics for latency that include ampicillin 2g IV once, followed by 1g IV every 6 hours for at least 48 hours, this is adequate for GBS prophylaxis 3
• If other antibiotic regimens are used for latency, GBS prophylaxis should be initiated in addition 3

For women with PPROM who are GBS positive:

• Continue antibiotics until delivery if in labor 3
• If not in labor, continue antibiotics per standard of care if receiving for latency, or continue antibiotics for 48 hours if receiving for GBS prophylaxis 3

For women with PPROM who are GBS negative:

• No GBS prophylaxis is needed at onset of true labor 3
• A negative GBS screen is considered valid for 5 weeks 3

Important Caveats and Considerations

• Amoxicillin/clavulanic acid should NOT be used due to increased risk of necrotizing enterocolitis in neonates 3, 1
• Azithromycin can be used as an alternative to erythromycin when erythromycin is not available 3
• Oral antibiotics alone are not adequate for GBS prophylaxis 3
• GBS prophylaxis should be discontinued at 48 hours for women with PPROM who are not in labor 3
• If GBS screen results become available during the 48-hour period and are negative, GBS prophylaxis should be discontinued at that time 3
• Women with PPROM should be screened for urinary tract infections, sexually transmitted infections, and GBS carriage, and treated with appropriate antibiotics if positive 1

Evidence of Effectiveness

• The recommended antibiotic regimen has been shown to:
  • Prolong pregnancy latency period 2, 4
  • Reduce rates of respiratory distress (40.5% vs 48.7%) 2
  • Reduce necrotizing enterocolitis (2.3% vs 5.8%) 2
  • Reduce overall sepsis in GBS-negative women (8.4% vs 15.6%) 2
  • Reduce rates of acute histologic chorioamnionitis and funisitis 4

Emerging Research

Recent research suggests that a new combination of ceftriaxone, clarithromycin, and metronidazole may be more effective against anaerobes and genital mycoplasmas frequently involved in PPROM, potentially improving outcomes further 4. However, this regimen is not yet included in current guidelines and would require additional validation before becoming standard practice.