Ampicillin Dosage for Premature Rupture of Membranes (PROM)
For preterm premature rupture of membranes (PPROM) at ≥24 weeks gestation, administer ampicillin 2g IV every 6 hours for 48 hours, followed by oral amoxicillin 250mg every 8 hours for 5 days, combined with erythromycin (or azithromycin if erythromycin unavailable). 1, 2
Standard Antibiotic Regimen for PPROM
The recommended 7-day course consists of: 1
Initial 48-hour IV phase:
Subsequent 5-day oral phase:
Alternative if erythromycin unavailable:
Gestational Age-Specific Considerations
PPROM at 20-23 6/7 weeks: The same antibiotic regimen can be considered to prolong latency and reduce neonatal morbidity, though evidence is stronger at later gestational ages 2
PPROM at >32 weeks: Antibiotics are recommended if fetal lung maturity cannot be proven and/or delivery is not immediately planned 3
Evidence for benefit is greatest at <32 weeks gestation 3
Group B Streptococcus (GBS) Prophylaxis Integration
The ampicillin dosing for latency (2g IV once, then 1g IV every 6 hours for at least 48 hours) provides adequate GBS prophylaxis: 1, 2
If GBS status unknown: Obtain vaginal-rectal swab and start the standard PPROM antibiotic regimen 2
If GBS positive: Continue antibiotics until delivery if in labor 1, 2
If GBS negative: No additional GBS prophylaxis needed at onset of true labor; negative screen valid for 5 weeks 1, 2
If not in labor: Discontinue GBS prophylaxis at 48 hours (but may continue latency antibiotics per clinical judgment) 2
Oral antibiotics alone are NOT adequate for GBS prophylaxis 2
Critical Contraindications and Alternatives
NEVER use amoxicillin/clavulanic acid (Augmentin) due to significantly increased risk of necrotizing enterocolitis in neonates. 1, 3 Amoxicillin without clavulanic acid is safe. 3
For penicillin-allergic patients:
- Without history of anaphylaxis/severe reaction: Cefazolin is preferred 4
- With history of anaphylaxis, angioedema, respiratory distress, or urticaria: Use macrolide antibiotics (erythromycin or azithromycin) alone 4, 3
Alternative Oral-Only Regimen
An alternative evidence-based regimen consists of: 3
- Erythromycin 250mg orally every 6 hours for 10 days
This oral-only approach showed benefit in large randomized trials, though the combined IV/oral regimen is more commonly recommended. 3
Recent Evidence on Enhanced Coverage
A 2025 randomized controlled trial demonstrated that ampicillin plus gentamicin is superior to ampicillin alone for term PROM (≥37 weeks), showing: 5
- Lower rates of clinical chorioamnionitis (1.0% vs 7.8%, NNT=14.7) 5
- Reduced intrapartum fever (8.0% vs 18.0%) 5
- Fewer neonatal adverse outcomes (10.8% vs 21.6%) 5
- Lower frequency of Enterobacteriaceae in chorioamniotic cultures (20% vs 51%) 5
While current guidelines have not yet incorporated this finding, it suggests consideration of adding gentamicin coverage, particularly at term gestation or when Enterobacteriaceae coverage is desired. 5
Clinical Benefits of Appropriate Therapy
Proper antibiotic administration in PPROM: 1
- Prolongs pregnancy latency 1, 6
- Reduces maternal infection and chorioamnionitis 1, 6
- Decreases neonatal morbidity and mortality 1, 6, 7
- Improves neonatal survival without severe morbidity 1
- Reduces neonatal infection rates (2% vs 17% in one study) 6
Additional Screening Requirements
Women with PPROM should be screened for: 3
Treat with appropriate antibiotics if positive. 3