Antibiotics for Preterm Premature Rupture of Membranes (PPROM)
Recommended Antibiotic Regimen
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
This regimen serves dual purposes: it prolongs pregnancy latency, reduces maternal infection and chorioamnionitis, decreases neonatal morbidity, and provides adequate Group B Streptococcus (GBS) prophylaxis when ampicillin is given at 2g IV initially followed by 1g IV every 6 hours for at least 48 hours. 3, 1, 4
Gestational Age-Specific Recommendations
PPROM at 24-34 Weeks
- Strongly recommended: Administer the full 7-day antibiotic course as described above 3, 1
- The evidence for benefit is greatest at earlier gestational ages (<32 weeks) 2
PPROM at 20-23 6/7 Weeks (Periviable)
- Antibiotics can be considered using the same regimen to prolong latency and reduce neonatal morbidity 3, 1
- This is a weaker recommendation (Grade 2C) due to limited data in this gestational age range 3
PPROM >32-34 Weeks
- Antibiotics are recommended if fetal lung maturity cannot be proven and/or delivery is not immediately planned 2
Alternative Antibiotic Options
When Erythromycin is Unavailable
- Azithromycin can substitute for erythromycin with no evidence of decreased efficacy and potential benefit in reducing chorioamnionitis rates 3, 1
Alternative Oral-Only Regimen
- Erythromycin 250mg orally every 6 hours for 10 days is an acceptable alternative regimen that has demonstrated decreased maternal and neonatal morbidity 2
Group B Streptococcus (GBS) Management
Initial Approach
- Obtain vaginal-rectal swab for GBS culture at admission and start antibiotics for latency 3, 4
- If receiving the standard ampicillin regimen (2g IV once, then 1g IV every 6 hours for ≥48 hours), this provides adequate GBS prophylaxis 3, 1, 4
If Patient Enters Labor
GBS-Positive or Unknown Status:
GBS-Negative:
- No additional GBS prophylaxis needed at labor onset 3, 4
- A negative GBS screen remains valid for 5 weeks 3, 4
If Patient Does NOT Enter Labor
- Continue antibiotics per standard latency protocol if receiving for latency 3
- Discontinue GBS prophylaxis at 48 hours if patient is not in labor and receiving antibiotics solely for GBS prophylaxis 3, 1, 4
- If GBS culture results become available during the 48-hour period and are negative, discontinue GBS prophylaxis immediately 3, 4
Critical Contraindications and Pitfalls
AVOID Amoxicillin-Clavulanic Acid
Amoxicillin-clavulanic acid is absolutely contraindicated due to increased risk of necrotizing enterocolitis in neonates. 3, 1, 2 Amoxicillin without clavulanic acid is safe. 2
Oral Antibiotics Alone Are Inadequate for GBS
- Oral antibiotics alone do not provide adequate GBS prophylaxis 1
- The IV ampicillin component is essential for GBS coverage 3, 1
Penicillin-Allergic Patients
Not at High Risk for Anaphylaxis
- Use cefazolin 2g IV initially, then 1g IV every 8 hours 5
High Risk for Anaphylaxis
- Perform susceptibility testing on GBS isolates 5
- If susceptible: clindamycin 900mg IV every 8 hours 5
- If resistant or susceptibility unknown: vancomycin 1g IV every 12 hours 5
Additional Screening and Treatment
Screen all women with PPROM for:
Treat with appropriate antibiotics if any are positive. 2
Important Clinical Considerations
- The standard antibiotic regimen prolongs pregnancy latency, reduces maternal infection and chorioamnionitis, decreases neonatal morbidity, and improves neonatal survival without severe morbidity 1
- Antibiotics should be administered promptly when indicated based on gestational age 1
- Recent evidence suggests that the current ampicillin-based regimen may not effectively eradicate vaginal Ureaplasma, with 75% of cases showing increased Ureaplasma levels after treatment 6, though this did not correlate with increased neonatal sepsis or bronchopulmonary dysplasia 6