What antibiotics are given to a patient with Preterm Premature Rupture of Membranes (PPROM)?

Antibiotic Management for PPROM

Primary Recommendation

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

---

Antibiotic Regimen Details

Standard Protocol (≥24 weeks)

• Initial 48-hour IV phase: Ampicillin 2g IV every 6 hours AND erythromycin 250mg IV every 6 hours 1
• Subsequent 5-day oral phase: Amoxicillin 250mg orally every 8 hours AND erythromycin 333mg orally every 8 hours 1
• This regimen prolongs pregnancy latency, reduces maternal infection and chorioamnionitis, decreases neonatal morbidity, and improves neonatal survival without severe morbidity 1

Alternative Regimen

• Erythromycin monotherapy: 250mg orally every 6 hours for 10 days is an acceptable alternative if the dual-drug regimen cannot be administered 2
• Azithromycin substitution: Can replace erythromycin when erythromycin is unavailable 1, 3

Gestational Age Considerations

• 20-23 6/7 weeks: The same antibiotic regimen carries a GRADE 2C recommendation, indicating weaker evidence at this earlier gestational age 1
• >32 weeks: Antibiotics to prolong pregnancy are recommended if fetal lung maturity cannot be proven and/or delivery is not planned 2
• The evidence for benefit is strongest at earlier gestational ages (<32 weeks) 2

---

Critical Contraindications

Never use amoxicillin/clavulanic acid (Augmentin) in PPROM patients, as it significantly increases the risk of necrotizing enterocolitis in neonates. 1, 2 Amoxicillin without clavulanic acid is safe 2

---

Group B Streptococcus (GBS) Prophylaxis Integration

If GBS Status Positive or Unknown

• The ampicillin 2g IV loading dose followed by 1g IV every 6 hours for at least 48 hours provides adequate GBS prophylaxis 1
• Continue antibiotics until delivery if the patient enters true labor 1
• Discontinue GBS prophylaxis at 48 hours if not in labor 1

If GBS Status Negative

• No additional GBS prophylaxis is needed at onset of true labor 1
• A negative GBS screen remains valid for 5 weeks 1
• If GBS results become available during the 48-hour period and are negative, discontinue GBS prophylaxis at that time 1

Important GBS Considerations

• Oral antibiotics alone are inadequate for GBS prophylaxis 1
• Women with PPROM should have vaginal-rectal swabs obtained for GBS culture if status is unknown 4

---

Special Populations

Penicillin Allergy

• Perform antibiotic susceptibility testing to guide alternative therapy 1
• For patients not at high risk for anaphylaxis, clindamycin or erythromycin can be used as alternatives 4
• In penicillin-allergic patients, macrolide antibiotics (erythromycin) should be used alone 2

Signs of Chorioamnionitis

• Switch to broad-spectrum antibiotics: Clindamycin plus gentamicin that include GBS coverage 1
• This regimen provides comprehensive coverage against aerobic gram-negative organisms and anaerobic bacteria 4, 5

---

Timing and Administration Principles

Critical Timing Thresholds

• Antibiotics are indicated after 18 hours of membrane rupture regardless of other risk factors 1, 4
• Prompt administration at hospital admission is essential when PPROM is diagnosed, not delayed until delivery decisions are made 1

If Cesarean Delivery Planned

• Administer antibiotics 30-60 minutes before skin incision to ensure therapeutic tissue concentrations 4, 5
• For cesarean delivery with ruptured membranes, adding azithromycin to cefazolin provides additional reduction in postoperative infections 4

---

Common Pitfalls to Avoid

• Delaying antibiotic initiation: Start immediately at hospital admission when PPROM is diagnosed, not when delivery is planned 1
• Using amoxicillin/clavulanic acid: This increases neonatal necrotizing enterocolitis risk 1, 2
• Relying on oral antibiotics alone for GBS prophylaxis: This is inadequate 1
• Confusing term PROM with preterm PROM protocols: The ampicillin/erythromycin regimen is specifically for preterm cases to prolong latency 5
• Failing to screen for concurrent infections: Screen for urinary tract infections, sexually transmitted infections, and GBS carriage, treating appropriately if positive 2

---

Evidence Quality Considerations

The ACOG recommendations are based on large randomized controlled trials demonstrating decreased maternal and neonatal morbidity with the dual-antibiotic regimen 1, 2. The evidence is strongest for gestational ages <32 weeks, with moderate to very low quality evidence for specific outcomes depending on the antibiotic comparison 6. Multiple antibiotics reduce chorioamnionitis rates, but the ampicillin plus erythromycin combination remains the standard based on consistent guideline recommendations and proven clinical benefit 1, 2, 3.