Early-onset sepsis (EOS) remains a significant cause of morbidity and mortality among newborns, particularly preterm infants, and requires ongoing surveillance for identification of changes in etiologic agents and antimicrobial resistance, according to study results published in JAMA Pediatrics.1

This prospective surveillance study included data from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from infants born between April 1, 2015, and March 31, 2017. Infants with a gestational age of ≥22 weeks and a birth weight >400 g were included in the study. The study outcome was EOS as determined by isolation of a pathogen from blood or cerebrospinal fluid culture obtained within 72 hours after birth and antibiotic treatment for ≥5 days or until death.

Of the 217,480 newborns identified during the 2-year study period, 235 were found to have EOS, reflecting an overall incidence of 1.08 (95% CI, 0.95-1.23) per 1000 live births.  Most infections (55.7%) occurred among preterm infants with a gestational age of <37 weeks. However, the incidence of EOS was highest among infants born at a gestational age of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000 live births). No significant differences in EOS based on sex, race, or ethnicity were identified.

A total of 86 infants (36.6%) were found to be infected with Escherichia coli, and 71 infants (30.2%) were infected with group B streptococcus (GBS). A greater incidence of E Coli infection was noted among preterm infants (51.9% [68 of 131]), and a greater incidence of GBS infection was noted among term infants (51.9% [54 of 104]). Of note, 24 of 45 infants (53.3%) infected with GBS were born to mothers with negative GBS screening test results.


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Mothers of approximately two-thirds of infected infants (162 of 235 [68.9%]) received intrapartum antibiotics, with administration differing based on gestational age (84% [110 of 131] of preterm cases vs 50% [52 of 104]of term cases [P<.001]). Reasons for antibiotic administration included suspected chorioamnionitis, premature rupture of membranes, prophylaxis for cesarean delivery, prophylaxis for GBS, and maternal fever.

Most infants were treated empirically with ampicillin and gentamicin, and isolates were found to be susceptible to one or both of these medications, “supporting the continued recommendation of ampicillin and gentamicin as empirical therapy for most infants at risk for EOS,” stated the researchers. Although gentamicin susceptibility did not differ between preterm and term infants, ampicillin-resistant E coli was noted more frequently among preterm infants vs term infants (83.1% vs 37.5%; P < .001).  Of 77 E coli isolates tested for susceptibility to ampicillin and gentamicin, 6 (7.8%) were found to be resistant to both antibiotics.

Signs of instability were identified within 72 hours after birth in 93.6% of infants with infection. All term infants survived; however, 38 of 131 (29.0%) infected infants with a gestational age <37 weeks died, including 27 infants with E coli infection.

Compared with an earlier Neonatal Research Network surveillance study (2006-2009),2no significant change was noted in the rate of GBS infection or infection-associated mortality; however, the E coli infection rate among infants with very low birth weight (401-1500 g) was higher in the current study (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P =.008).  In addition, resistance to gentamicin increased from 3% to 11% in the years since the earlier study.

Most instances of preterm neonatal E coli or GBS infection were associated with preterm rupture of membranes with or without preterm labor, and approximately half of mothers had a clinical diagnosis of chorioamnionitis. “These findings support approaches to neonatal risk assessment among term and late preterm infants that use a combination of perinatal risk factors and clinical condition,” noted the researchers.

“Continued surveillance is warranted to identify changes in pathogen distribution and/or antibiotic susceptibilities,” concluded the researchers. “Novel prevention strategies, including efforts to prevent intra-amniotic infection, are needed to effect further declines in the incidence of early-onset infection.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Stoll BJ, Puopolo KM, Hansen NI, et al; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.Early-onset neonatal sepsis 2015 to 2017, the rise of Escherichia coli, and the need for novel prevention strategies [published online May 4, 2020]. JAMA Pediatr. doi:10.1001/jamapediatrics.2020.0593

2. Stoll BJ, Hansen NI, Sánchez PJ, et al; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics. 2011;127(5):817-826.