What antibiotic regimen is recommended for the management of Premature Preterm Rupture of Membranes (PPROM)?

Antibiotic Regimen for Premature Preterm Rupture of Membranes (PPROM)

For PPROM management, the recommended antibiotic regimen is a 7-day course consisting of intravenous ampicillin and erythromycin for 48 hours followed by oral amoxicillin and erythromycin for an additional 5 days. 1

Recommended Antibiotic Protocol

For PPROM at ≥24 weeks gestation (Strong recommendation, Grade 1B):

• Initial 48 hours:

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

• Followed by 5 additional days:

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

Alternative regimen:

• Erythromycin 250mg orally every 6 hours for 10 days 2

Azithromycin substitution:

• Azithromycin can be used as an alternative to erythromycin when erythromycin is not available 1, 3

Important Considerations

• Avoid amoxicillin-clavulanic acid as it has been associated with increased risk of necrotizing enterocolitis in neonates 1, 2

• For PPROM at 20 0/7 to 23 6/7 weeks gestation:

  • Antibiotics can be considered (weaker recommendation, Grade 2C) 1
  • Evidence shows surviving neonates were more likely born to pregnant persons who received antibiotics 1

• For GBS prophylaxis in PPROM:

  • The ampicillin regimen used for PPROM latency (2g IV once, followed by 1g IV every 6 hours for at least 48 hours) is adequate for GBS prophylaxis 1
  • If other antibiotic regimens are used that don't provide adequate GBS coverage, additional GBS prophylaxis should be initiated 1

Duration of Therapy

• For women with PPROM who are not in labor:

  • Continue antibiotics for the full 7-day course 1
  • GBS prophylaxis should be discontinued after 48 hours if not in labor 1

• For women entering labor during antibiotic treatment:

  • Continue antibiotics until delivery 1

Evidence Quality and Effectiveness

• The recommended regimen is based on randomized clinical trials showing decreased maternal and neonatal morbidity 1

• Network meta-analysis shows several antibiotics are more effective than placebo in reducing chorioamnionitis after PPROM, with clindamycin + gentamicin showing the strongest effect (RR 0.19), followed by penicillin (RR 0.31) and ampicillin (RR 0.52) 4

• Erythromycin was the only effective drug for reducing neonatal sepsis in meta-analysis (RR 0.74) 4

• The benefit of antibiotics is greater at earlier gestational ages (<32 weeks) 2

Monitoring During Antibiotic Treatment

• Monitor for signs of infection including maternal fever, uterine tenderness, fetal tachycardia, and malodorous vaginal discharge 3

• Perform regular maternal vital signs, fetal heart rate monitoring, physical examination, and laboratory evaluation for signs of infection 3

• Patients should monitor their temperature daily and report signs of PPROM complications including vaginal bleeding, discolored or malodorous discharge, and abdominal pain 3

Pitfalls to Avoid

• Do not use amoxicillin-clavulanic acid due to increased risk of necrotizing enterocolitis 1, 2

• Do not rely on oral antibiotics alone for GBS prophylaxis as they are inadequate 1

• Do not discontinue antibiotics if patient is determined to be in true labor 1

• Do not forget to screen for urinary tract infections, sexually transmitted infections, and group B streptococcus carriage, and treat with appropriate antibiotics if positive 2