PIDS Journal Club – Early-Onset Neonatal Sepsis 2015-2017

Author:

  • Sanjeev K. Swami MD. Associate Professor of Clinical Pediatrics, Division of Infectious Diseases, Children’s Hospital of Philadelphia

Reviewers:

  • John S. Schieffelin, MD, MSPH. Associate Professor of Pediatrics and Internal Medicine, Sections of Infectious Disease, Tulane University School of Medicine
  • Christine Salvatore MD, MS. Associate Professor of Clinical Pediatrics, Weill Cornell Medical College, Cornell University

Early-Onset Neonatal Sepsis 2015-2017, the Rise of Escherichia coli, and the need for Novel Prevention Strategies

  • Barbara J. Stoll, MD1; Karen M. Puopolo, MD, PhD2; Nellie I. Hansen, MPH3; et al JAMA Pediatr. 2020;174(7):e200593. doi:10.1001/jamapediatrics.2020.0593

Background:

Early onset neonatal sepsis (EOS) remains a leading cause of morbidity and mortality in children. Intrapartum antibiotic prophylaxis (IAP) to prevent EOS due to Group B streptococcus (GBS) has significantly reduced the rates of invasive GBS disease, but there has been concern about increasing rates of ampicillin resistant E. coli infections, especially in preterm infants. A prior study of EOS showed that most cases occurred in term infants, but the incidence rate and mortality were higher among preterm infants1. This study examined a 2 year birth cohort to update the rates of infection, pathogen distribution, antibiotic susceptibilities, and outcomes in preterm and term neonates.

Methods and Results:

This prospective observational study used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN). Surveillance for EOS and early onset meningitis was performed at 18 NRN centers. All infants with gestational age greater than 22 weeks and birth weight greater than 400 g born between April 1, 2015 and March 21, 2017 were included. EOS was defined as growth of a pathogen in blood culture within 72 hours of birth and treatment with antibiotics for at least 5 days or until death. Meningitis was defined using the same criteria except with isolation of a pathogen from the cerebral spinal fluid.

There were 235 cases of EOS and 6 cases of early onset meningitis in 217,480 live births; there were 86 infections due to E. coli and 71 due to GBS. 131 cases of EOS were in preterm infants and 104 cases occurred in term infants. Gram negative pathogens were more common in preterm infants while Gram positive organisms caused most cases of EOS in term infants. In preterm infants, episodes of EOS were due to E. coliin 52% infants while GBS was the cause in 13%. Conversely, E. coli caused EOS in 15% of term infants while GBS caused 52% of EOS episodes. The rate of EOS was highest among very low birth weight (VLBW) infants (13.9/1,000) and those in the youngest gestational age group (22 to 28 weeks; 18.5/1000).

All tested GBS isolates were susceptible to penicillin, ampicillin, and vancomycin, but only 58% (18 of 31) were susceptible to clindamycin. Only 26% of the E. coli isolates tested against ampicillin were susceptible. Infants born to mothers who had received intrapartum ampicillin were more likely to have ampicillin-resistant E. coli compared to babies born to mothers who did not receive intrapartum ampicillin (82% vs. 65%). 6 of 77 E. coli isolates tested against ampicillin and gentamicin were resistant to both (8%). 95% of E. coli isolates were susceptible to 3rd generation cephalosporins.

45 of 70 mothers with infants with EOS due to GBS were screened for GBS prior to delivery. 24 of these women had negative results: 23 term infants with GBS EOS (72%), 1 preterm infant (8%). 106 mothers had an indication for GBS IAP, 83 received antibiotics (78%). There were 40 mothers who had an indication for IAP who had an infant with EOS due to GBS; 15 did not receive IAP (38%).

Mothers of infants with E. coli EOS were more likely to have received antibiotics within 72 hours of delivery and have rupture of membranes greater than 18 hours compared to mothers whose infants had GBS EOS. 94% of infants with EOS had signs of disease within 72 hours of birth. All of the infants received antibiotics except for 1 infant who died shortly after birth. 38 infants with EOS died, all were in the preterm group (27 had E. coli infection). There were 2 infants who died due to E. coli strains that were resistant to ampicillin and gentamicin, the infants were receiving those antibiotics at the time of their deaths. 

The rates of infection were compared to a similar cohort from 2006 to 2009 among the 14 centers the participated in both studies1. The rate of EOS among VLBW increased significantly between the two time periods. There was no change in rates of GBS infection but there was a significant increase in the rate of E. coliinfections in VLBW infants.

Comments:

This study updates the epidemiology of EOS in preterm and term infants from 2015 to 2017. The authors found that rates of EOS were highest in preterm infants and that these infants were at higher risk for fatal outcomes compared to term infants with EOS. Preterm infants were more likely to have infection due to E. coli or other Gram negative organisms and antibiotic resistance is increasingly prevalent among those isolates including 2 strains of E. coli that were resistant to ampicillin and gentamicin. Continued surveillance of these trends is vital. There were also a number of missed opportunities for GBS prevention and it remains a significant pathogen in this patient population. Additional interventions to decrease rates of intra-uterine infection and preterm labor in pregnant women are needed. Interestingly, the authors did not find different rates of infection based on race or ethnicity compared to prior studies that have showed that infants born to black mothers have higher rates of EOS1,2. The study sites were predominantly academic centers; although these data represent a large U.S. birth cohort, the results may not be generalizable to smaller community hospitals and nonacademic centers.

References:

  1. Stoll BJ, Hansen NI, Sanchez PJ et al; 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. DOI: https://doi.org/10.1542/peds.2010-2217
  2. Schrag SJ, Farley MM, Petit A. et al. Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014. Pediatrics. 2016;138(6):e20162013. DOI: https://doi.org/10.1542/peds.2016-2013

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