What are the recommended antibiotics for Premature Preterm Rupture of Membranes (PPROM)?

Recommended Antibiotics for PPROM

For PPROM at ≥24 weeks gestation, administer a 7-day course consisting of IV ampicillin 2g every 6 hours plus erythromycin 250mg IV every 6 hours for 48 hours, followed by oral amoxicillin 250mg every 8 hours plus erythromycin 333mg every 8 hours for 5 days. 1, 2

Standard Antibiotic Regimen

The evidence-based protocol is straightforward and should be initiated immediately upon diagnosis:

• Initial 48 hours (IV phase):

  • Ampicillin 2g IV every 6 hours 1, 2, 3
  • Erythromycin 250mg IV every 6 hours 1, 2, 3

• Days 3-7 (oral phase):

  • Amoxicillin 250mg orally every 8 hours 1, 2, 3
  • Erythromycin 333mg orally every 8 hours 1, 2, 3

This regimen is strongly recommended (GRADE 1B) by both ACOG and SMFM for PPROM at ≥24 weeks gestation. 1, 3

Alternative Macrolide Option

• Azithromycin can substitute for erythromycin when erythromycin is unavailable. 1, 2, 3
• This substitution maintains efficacy while addressing supply chain issues that commonly affect erythromycin availability. 1

Gestational Age-Specific Recommendations

• PPROM at 20-23 6/7 weeks: Antibiotics can be considered using the same regimen, though evidence is weaker (GRADE 2C). 2, 3
• PPROM at ≥24 weeks: Strong recommendation for immediate antibiotic initiation (GRADE 1B). 1, 3
• PPROM >32 weeks: Antibiotics recommended if fetal lung maturity cannot be proven and/or delivery is not immediately planned. 4

Critical Contraindication

Never use amoxicillin-clavulanic acid (Augmentin) in PPROM—it significantly increases the risk of neonatal necrotizing enterocolitis. 1, 2, 3, 4 Amoxicillin without clavulanic acid is safe and appropriate. 4

Integration with GBS Prophylaxis

The standard PPROM antibiotic regimen provides adequate GBS coverage during the initial 48-hour IV phase:

• If the regimen includes ampicillin 2g IV once, followed by 1g IV every 6 hours for ≥48 hours, this satisfies GBS prophylaxis requirements. 2, 3
• GBS-positive women: Continue antibiotics until delivery if in labor. 2, 3
• GBS-negative women: No additional GBS prophylaxis needed at labor onset; negative screen valid for 5 weeks. 2, 3
• Unknown GBS status: Obtain vaginal-rectal swab and start the standard PPROM regimen. 3
• If GBS results return negative during the 48-hour period, discontinue GBS prophylaxis at that time. 2, 3
• Oral antibiotics alone are inadequate for GBS prophylaxis. 2, 3

Mechanism of Benefit

The primary benefits of this antibiotic regimen include:

• Direct prevention of neonatal sepsis (8.4% vs 15.6% in GBS-negative women, P=0.01). 1
• Prolongation of pregnancy latency, allowing additional fetal lung maturation. 1
• Reduction in maternal chorioamnionitis and infection. 1, 5
• Decreased neonatal respiratory distress syndrome and overall morbidity. 1, 2
• Antibiotics administered ≥4 hours before delivery are highly effective at preventing vertical GBS transmission. 1

Common Pitfalls to Avoid

• Do not delay antibiotic initiation in PPROM ≥24 weeks—evidence strongly supports immediate administration. 1
• Do not extend or repeat antibiotic courses beyond the standard 7-day regimen to optimize antibiotic stewardship. 1
• Do not use prolonged courses without clear indication, as this increases resistance without additional benefit. 1
• Do not administer broad-spectrum antibiotics in term PROM before 18 hours unless other indications exist (e.g., GBS-positive, chorioamnionitis). 1

Penicillin Allergy Considerations

• Perform antibiotic susceptibility testing to guide alternative therapy in penicillin-allergic patients. 2
• In penicillin allergy, use macrolide antibiotics (erythromycin or azithromycin) alone. 4

Additional Screening

• Screen all women with PPROM for urinary tract infections, sexually transmitted infections, and GBS carriage, treating appropriately if positive. 4