To further address this issue, the MFMU Network designed a trial to study expectant management combined with placebo or with a 7 -day antibiotic regimen. Treatment included intravenous ampicillin plus erythromycin every 6 hours for 48 hours, which was followed by oral amoxicillin plus erythromycin, every 8 hours for 5 days. The women had membrane rupture between 24 and 32 weeks' gestation. Neither tocolytics nor corticosteroids were given. Antimicrobial-treated women had signiicantly fewer newborns with RDS, necrotizing enterocolitis, and composite adverse outcomes (Mercer, 1997). The latency period was also significantly longer. Specifically, 50 percent of women given an antimicrobial regimen remained undelivered after 7 days of treatment compared with only 25 percent of those given placebo. lso, a significantly greater number of treated pregnancies were undelivered at 14 and 21 days. Cervico vaginal group B streptococcal colonization did not alter these results.
Other studies have examined the eicacy of shorter treatment lengths and diferent antimicrobial combinations. hreeday treatments compared with 7 -day regimens using either ampicillin or ampicillin-sulbactam appear equally efective in regard to perinatal outcomes (Lewis, 2003; Segel, 2003). Similarly, erythromycin compared with placebo ofered a range of significant neonatal benefits. The amoxicillin-clavulanate regimen was not recommended, however, because of its association with an increased incidence of neonatal necrotizing enterocolitis (Kenyon, 2004).
Some predicted that prolonged antimicrobial therapy in such pregnancies might have unwanted consequences (Carroll, 1996; Mercer, 1999). Stoll and associates (2002) studied 4337 neonates weighing from 400 to 1500 g and born from 1998 to 2000. Their outcomes were compared with those of 7606 neonates of similar birthweight born from 1991 to 1993 and prior to the practice of antibiotic prophylaxis. The overall rate of early-onset sepsis did not change between these two epochs. But, the rate of group B streptococcal sepsis dropped from 5.9 per 1000 births in the 1991 to 1993 group to 1.7 per 1000 births in the 1998 to 2000 group. Comparing these same epochs, the rate of Escherichia coli sepsis, however, rose from 3.2 to 6.8 per 1000 births. Almost 85 percent of coliform isolates from the more recent cohort were resistant to ampicillin. Neonates with early-onset sepsis were more likely to die, especially if they were infected with coliforms. Long term, Kenyon and coworkers (2008a) found that antimicrobials given for women with PPROM had no efect on the health of children at age 7 years .
• Corticosteroids to Accelerate