During the 1990's, the pattern of early infections among very low birth weight (VLBW) infants changed significantly, according to a National Institute of Child Health and Human Development (NICHD)- funded study that appears in the current issue of the New England Journal of Medicine. Specifically, the proportion of early infections caused by a group of disease-causing organisms known as gram-negative bacteria increased, while the proportion of early infections caused by another group of disease-causing organisms called gram-positive bacteria decreased. Gram negative infections tend to be more lethal and more resistant to antibiotics than gram positive infections.
The study, by Barbara J. Stoll, M.D. and colleagues, looked at newborn infection rates among VLBW infants (infants weighing between 401 and 1500 grams) born at centers of the Neonatal Research Network of the NICHD. The study was conducted in order to examine whether the rates and causes of early-onset sepsis (newborn infection within 72 hours after birth) among VLBW infants have changed in recent years since antibiotics have begun to be used more widely during labor and delivery to prevent newborn group B streptococcal (GBS) infection and other complications.
"Early-onset infections are an important cause of illness and death among VLBW infants," said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development. "Further surveillance may be needed to determine if reducing some types of newborn infection through the use of maternal antibiotics is accompanied by an increase in the risk of newborn infection with more harmful organisms."
The researchers studied 5,447 VLBW infants born at centers of the Neonatal Research Network of the NICHD between 1998 and 2000 and compared them with 7,606 VLBW infants born at Neonatal Network centers between 1991 and 1993. They found that the overall rate of early-onset sepsis among VLBW infants did not decline significantly between the two time periods studied. Additionally, there were no differences in the rates of early infection between infants whose mothers received antibiotics during labor and delivery and those who did not. However, there was a significant change in the types of bacteria causing newborn infections. While gram-positive bacteria, including GBS, caused the majority of early-onset infections between 1991 and 1993, gram-negative bacteria, and E. coli in particular, were the most frequent cause of early-onset infections between 1998 and 2000.
Most (85 percent) of the isolates of E. coli from infected infants in the recent group of VLBW infants were resistant to ampicillin, a common antibiotic. The mothers of infants with ampicillin-resistant E. coli infections were significantly more likely to have received ampicillin during labor and delivery than mothers of infants with ampicillin-sensitive E. coli infection (93 percent versus 20 percent). All of the E. coli isolates tested in the recent cohort were sensitive to third-generation cephalosporins, a more expensive group of antibiotics that may be used to treat infections that are resistant to other antibiotics.
Although early-onset sepsis occurs in less than 2 percent of all VLBW infants, it is a significant cause of illness and death among newborns. In the current study, infants with early-onset sepsis had significantly higher risks of respiratory distress syndrome, other neonatal complications, and were more likely to die than uninfected infants (37 percent versus 13 percent).
"The significant increase in recent years in the use of antibiotics during labor and delivery is due in part to national programs designed to reduce the spread of GBS infection from mother to child, as well as to reduce the risk of neonatal medical complications that often occur in VLBW infants," said Linda L. Wright, M.D., one of the study's authors and Deputy Director of NICHD's Center for Research for Mothers and Children. "In fact, our study showed that the rate of GBS infection among VLBW infants did decline in the 1990's. However, we also saw a significant increase in the rate of newborn infection with gram-negative organisms such as E. coli. This is troubling because gram-negative sepsis is particularly lethal and is also more likely to be antibiotic-resistant."
The authors of the study recommend further surveillance to confirm the observed change in the types of bacteria causing early-onset sepsis in VLBW infants.
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The NICHD is part of the National Institutes of Health, the biomedical research arm of the federal government. The Institute sponsors research on development, both before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD Information Resource Center, 1-800-370-2943; E-mail NICHDInformationResourceCenter@mail.nih.gov.
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