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ABSTRACT & COMMENTARY
To determine if antibiotic treatment during expectant management of preterm premature rupture of the membranes (PPROM) will reduce infant morbidity, Mercer and colleagues conducted a randomized, double-blind, placebo-controlled trial of 614 gravidas with PPROM between 24 and 32 weeks gestation. Women were randomized to receive either intravenous ampicillin (2 g every 6 hours) and erythromycin (250 mg every 6 hours) for 48 hours intravenously followed by oral amoxicillin (250 mg every 8 hours) and erythromycin base (333 mg every 8 hours) for five days or a matching placebo. Patients were cultured for Group B streptococcus (GBS) and treated if culture-positive. Tocolytics and corticosteroids were not administered after randomization. Fetal or infant mortality, respiratory distress (RD), severe intraventricular hemorrhage (IVH), serious necrotizing enterocolitis (NEC), or sepsis within 72 hours of birth were considered significant adverse outcomes.
The infants of women who were GBS-negative benefitted significantly from maternal antibiotic therapy, with reductions in overall morbidity, including RD, sepsis, NEC, and pneumonia. Pregnancy was significantly prolonged in the treated group, with twice as many women remaining undelivered after PPROM (24.4% vs 12.1% at 14 days and 14.3% vs 7% at 21 days). The incidence of clinical amnionitis was significantly lower in mothers who received antibiotics. No significant morbidity for either the mother or infant was observed in the antibiotic-treated group. Mercer and associates conclude that antibiotic treatment of women managed expectantly after PPROM at 24-32 weeks gestation will reduce infectious morbidity and prolong pregnancy. Antibiotics should be administered to these patients regardless of GBS carrier status.
Approximately one-third of all preterm births are due to PPROM. Intrauterine infection is thought to be the cause of most cases of PPROM, especially between 24 and 32 weeks gestation. When managing PPROM, the clinician hopes to delay delivery, recognizing that although the major risk to the infant at this gestational age is prematurity, expectant management may increase infectious morbidity in both the mother and baby. Mercer et al have demonstrated that a combination of intravenous ampicillin and erythromycin for 48 hours followed by five days of oral amoxicillin and erythromycin base significantly reduce infant morbidity and prolong gestation in women who are GBS-negative and would otherwise not receive prophylactic antibiotics before labor. This antibiotic regimen was selected to give broad antimicrobial coverage including ureaplasma. Not surprisingly, this protocol did not benefit infants of women who were GBS-positive, as their mothers received GBS prophylaxis. Antibiotics were administered for only seven days to reduce the likelihood that a resistant organism would be selected. Ampicillin-resistant E. coli sepsis causing neonatal death has been reported. Since the completion of this study, the National Institute of Child Health and Human Health Development Consensus Conference has recommended corticosteroid administration after PPROM for pregnancies at less than 30-32 weeks gestation to reduce the risk of IVH. While corticosteroids were not used in the present study, it is possible they would have provided further benefit to the neonates beyond that associated with prolongation of the pregnancy.
In summary, I would agree with Mercer et al that antibiotic coverage of the type used in this study be offered to women with PPROM at a gestational age of 24-32 weeks regardless of GBS carrier status.