Epidemiology of Invasive Early-Onset Neonatal Sepsis, 2005 to 2014 - American Academy of Pediatrics
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Epidemiology of Invasive Early-Onset
Neonatal Sepsis, 2005 to 2014
Stephanie J. Schrag, DPhil,a Monica M. Farley, MD,b,c Susan Petit, MPH,d Arthur Reingold, MD,e
Emily J. Weston, MPH,a Tracy Pondo, MSPH,a Jennifer Hudson Jain, MPH,a Ruth Lynfield, MDf
BACKGROUND: Group B Streptococcus (GBS) and Escherichia coli have historically dominated as abstract
causes of early-onset neonatal sepsis. Widespread use of intrapartum prophylaxis for GBS
disease led to concerns about the potential adverse impact on E coli incidence.
METHODS: Active, laboratory, and population-based surveillance for culture-positive (blood
or cerebrospinal fluid) bacterial infections among infants 0 to 2 days of age was conducted
statewide in Minnesota and Connecticut and in selected counties of California and Georgia
during 2005 to 2014. Demographic and clinical information were collected and hospital live
birth denominators were used to calculate incidence rates (per 1000 live births). We used
the Cochran–Amitage test to assess trends.
RESULTS: Surveillance identified 1484 cases. GBS was most common (532) followed by E coli
(368) and viridans streptococci (280). Eleven percent of cases died and 6.3% of survivors
had sequelae at discharge. All-cause (2005: 0.79; 2014: 0.77; P = .05) and E coli (2005: 0.21;
2014: 0.18; P = .25) sepsis incidence were stable. GBS incidence decreased (2005: 0.27;
2014: 0.22; P = .02). Among infantsInfections in the first 3 days of Bacterial Core surveillance/Emerging estimate those in 2008. Among the life (early onset) remain among Infections Program network live birth denominator data, missing the leading causes of infant death established active, population-based values for race (8%), gestational age in the United States and can surveillance for early-onset invasive (1%), and birth weight (
(very low birth weight:
TABLE 1 Characteristics of Newborns With Invasive Sepsis in the First 3 Days of Life, Active Bacterial 95% CI: 6.5%–9.0%), and suspected
Core Surveillance Neonatal Sepsis Activity, 2005 to 2014 maternal chorioamnionitis (cases:
Characteristic Overall (%, n = GBS (%, n = 532) E coli (%, n = 368) Pa 29.9%; 95% CI: 25.4%–34.5% versus
1484) population: 3.4%; 95% CI: 2.5%–
Surveillance areaTABLE 1 Continued not significantly more likely than
Characteristic Overall (%, n = GBS (%, n = 532) E coli (%, n = 368) Pa GBS to result in death (odds ratio
1484) [OR]: 1.3; 95% CI: 0.7–2.2). Among
Pneumonia 5.0 7.0 4.6 preterm infants with E coli infection,
Other 7.9 4.4 7.8 27% of deaths (21/77) occurred on
Sterile site
day 0 and 31% (24/77) on day 1;
Blood only 97.8 98.3 97.0
CSF only 0.9 (n = 14) 0.6 (n = 3) 0.3 (n = 1) 86% of these deaths (66/77) were
Blood and CSF 1.3 (n = 19) 1.1 (n = 6) 2.7 (n = 10) exposed to intrapartum antibiotics.
Length of hospitalization (d, 10 (6–22) 10 (9–14) 17 (9–50)GBS prophylaxis has not resulted
in an increase in Gram-negative
sepsis. Moreover, reports from
the early years of GBS prevention
raising concern about increasing E
coli incidence among very low birth
weight or preterm infants are not
borne out by our observations. More
recent observations from single
institutions and hospital networks
are consistent with our results.12,13
GBS remained the most common
invasive early-onset pathogen in
each surveillance year, followed by
E coli, with other pathogens notably
less frequent. An assessment of
implementation of perinatal GBS
disease prevention guidelines in
these surveillance areas among
a representative sample of live
births in 2003 to 2004 already
showed strong implementation
of universal antenatal screening
and administration of intrapartum
prophylaxis to colonized women.3
The case-only data presented in
this study do not reflect population-
level implementation because it is
enriched for implementation failures;
our data do suggest that there may
be potential for small additional
decreases in GBS incidence based on
the observation that 37% of cases
with an indication for prophylaxis did
not receive it.
Although overall GBS remained the
FIGURE 2
leading pathogen across surveillance A, Invasive early-onset GBS disease incidence by gestational age categories, 2005 to 2014, Active
years, the CIs around the incidence Bacterial Core surveillance. B, Invasive early-onset E coli disease incidence by gestational age
rates for GBS and E coli overlapped. categories, 2005 to 2014, Active Bacterial Core surveillance.
In the most recently reported years
of multisite surveillance from the report E coli as the most common in the context of management and
National Institute of Child Health and cause of invasive early-onset sepsis12; prevention strategies.
Development’s Neonatal Research moreover, in one of the surveillance
Network (2009),14 and the large areas (California), E coli was more Early-onset sepsis incidence was
Pediatrix network (2010),13 GBS common than GBS for all surveillance significantly higher among black
early-onset incidence also remained term infants with less evident
years. Additionally, a study from
higher than that of E coli. Nationwide differences for infants 34 to 36
2005 to 2012 of bacteremia among
surveillance in the Netherlands15 weeks of gestation andwas documented in two-thirds of our
cases, may contribute to the severity
of E coli outcomes,18
although on univariate analysis,
death among infants with E coli
was not associated with ampicillin
resistance. Aminoglycoside
resistance remained rare but notably,
gentamicin resistance was strongly
associated with ampicillin resistance,
highlighting the importance of
continued evaluation of regimens
for first-line early-onset sepsis
treatment.19 Our observation that
more than half of preterm E coli
cases died very close to birth, despite
exposure to intrapartum prophylaxis,
further supports this need.
A number of maternal, intrapartum,
and demographic features differed
between invasive GBS and E coli
cases in univariate analysis. Black
race (more common among GBS
cases) and prolonged membrane
rupture and intrapartum antibiotic
exposure (more common among
E coli cases) were the only
factors that remained when
controlling for gestational age. The
overrepresentation of intrapartum
antibiotic exposure among infants
with E coli infection compared
with those with GBS may reflect,
in part, that intrapartum regimens
used for GBS prevention (most
typically penicillin or ampicillin) are
not effective in preventing early-
onset E coli infections. The high
FIGURE 3 proportion of chorioamnionitis in
A, Invasive early-onset GBS disease incidence by birth weight categories, 2005 to 2014, Active Bacterial
this group suggests that intrapartum
Core surveillance. B, Invasive early-onset E coli disease incidence by birth weight categories, 2005 to
2014, Active Bacterial Core surveillance. intervention may be too late for
prevention but may still hold value
birth weight infants. Consistent with death. However, among infants for initiation of early newborn
other recent surveillance,9,13,14 ≥1500 g at birth, where death was treatment.
E coli was associated with most less frequent, E coli infections were Although our surveillance
early-onset sepsis deaths, primarily associated more often with severe benefitted from a large, population-
due to its predominance among outcomes. The large catchment in based catchment population and
very low birth weight infants. For our surveillance may have given detailed labor and delivery record
this subpopulation, E coli was not us the power to detect this trend, review to capture intrapartum
significantly more likely to result which was not noted in other, histories, it captured only limited
in death than GBS. It is likely in smaller studies.14,16 Clonal changes clinical information on disease
this vulnerable population that among E coli associated with early- management and course. Maternal
pathogen virulence may not be onset sepsis and, in particular, chorioamnionitis was also only
strongly associated with risk of emerging ampicillin resistance, which collected from 2011 to 2014.
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PEDIATRICS Volume 138, number 6, December 2016 7TABLE 2 Univariate Factors Associated With Mortality Among Infants With Invasive Early-Onset burden of E coli early-onset sepsis
Sepsis, Active Bacterial Core Surveillance, 2005 to 2014 we observed underscores the need
Characteristic Died (n = 165), % Survived (n = 1319), % OR (95% CI) for a prevention strategy. Although
Exposed Exposed our surveillance identifies that many
Pathogen of the risk factors identified for GBS
GBS 22.4 37.5 Referent are similar for E coli, intrapartum
E coli 51.5 21.5 4.0 (2.7–6.1) prophylaxis has not resulted in
Other 26.1 41.0 1.1 (0.7–1.7)
declines, consistent with previous
Birth weight6. Towers CV, Briggs GG. Antepartum use Francisco and Atlanta. Pediatrics. a 4-year, population-based study.
of antibiotics and early-onset neonatal 2002;110(4):690–695 J Matern Fetal Neonatal Med.
sepsis: the next 4 years. Am J Obstet 12. Bizzarro MJ, Shabanova V, Baltimore 2016;29(19):3126–3131
Gynecol. 2002;187(2):495–500 RS, Dembry LM, Ehrenkranz RA, 17. Biondi E, Evans R, Mischler M, et al.
7. Towers CV, Carr MH, Padilla G, Asrat T. Gallagher PG. Neonatal sepsis 2004- Epidemiology of bacteremia in febrile
Potential consequences of widespread 2013: the rise and fall of coagulase- infants in the United States. Pediatrics.
antepartal use of ampicillin. Am J negative staphylococci. J Pediatr. 2013;132(6):990–996
Obstet Gynecol. 1998;179(4): 2015;166(5):1193–1199
18. Weissman SJ, Hansen NI, Zaterka-
879–883 13. Bauserman MS, Laughon MM, Hornik Baxter K, Higgins RD, Stoll BJ.
8. Stoll BJ, Hansen N, Fanaroff AA, CP, et al. Group B Streptococcus and Emergence of antibiotic resistance-
et al. Changes in pathogens causing Escherichia coli infections in the associated clones among Escherichia
early-onset sepsis in very-low- intensive care nursery in the era of coli recovered from newborns
birth weight infants. N Engl J Med. intrapartum antibiotic prophylaxis. with early-onset sepsis and
2002;347(4):240–247 Pediatr Infect Dis J. 2013;32(3):208–212 meningitis in the United States,
9. Bizzarro MJ, Dembry LM, Baltimore 14. Stoll BJ, Hansen NI, Sanchez PJ, et 2008-2009. J Pediatric Infect Dis Soc.
RS, Gallagher PG. Changing patterns al. Early onset neonatal sepsis: the 2015;5(3)269–276
in neonatal Escherichia coli sepsis burden of group B Streptococcal and 19. Kent A, Kortsalioudaki C, Monahan
and ampicillin resistance in the era E. coli disease continues. Pediatrics. IM, et al. Neonatal gram-negative
of intrapartum antibiotic prophylaxis. 2011;127(5):817–826 infections, antibiotic susceptibility and
Pediatrics. 2008;121(4):689–696 15. Bekker V, Bijlsma MW, van de Beek D, clinical outcome: an observational
10. Joseph TA, Pyati SP, Jacobs N. Kuijpers TW, van der Ende A. Incidence study [published online ahead of
Neonatal early-onset Escherichia coli of invasive group B streptococcal print March 7, 2016]. Arch Dis Child
disease. The effect of intrapartum disease and pathogen genotype Fetal Neonatal Ed. doi:10.1136/
ampicillin. Arch Pediatr Adolesc Med. distribution in newborn babies in archdischild-2015-309554
1998;152(1):35–40 the Netherlands over 25 years: a 20. Schrag SJ, Hadler JL, Arnold KE,
11. Hyde TB, Hilger TM, Reingold A, Farley nationwide surveillance study. Lancet Martell-Cleary P, Reingold A, Schuchat
MM, O’Brien KL, Schuchat A. Trends Infect Dis. 2014;14:1083–1089 A. Risk factors for invasive, early-onset
in incidence and antimicrobial 16. Berardi A, Baroni L, Bacchi Reggiani Escherichia coli infections in the era
resistance of early-onset sepsis: ML, et al. The burden of early-onset of widespread intrapartum antibiotic
population-based surveillance in San sepsis in Emilia-Romagna (Italy): use. Pediatrics. 2006;118(2):570–576
Downloaded from www.aappublications.org/news by guest on December 29, 2020
PEDIATRICS Volume 138, number 6, December 2016 9Epidemiology of Invasive Early-Onset Neonatal Sepsis, 2005 to 2014
Stephanie J. Schrag, Monica M. Farley, Susan Petit, Arthur Reingold, Emily J.
Weston, Tracy Pondo, Jennifer Hudson Jain and Ruth Lynfield
Pediatrics 2016;138;
DOI: 10.1542/peds.2016-2013 originally published online November 29, 2016;
Updated Information & including high resolution figures, can be found at:
Services http://pediatrics.aappublications.org/content/138/6/e20162013
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Downloaded from www.aappublications.org/news by guest on December 29, 2020Epidemiology of Invasive Early-Onset Neonatal Sepsis, 2005 to 2014
Stephanie J. Schrag, Monica M. Farley, Susan Petit, Arthur Reingold, Emily J.
Weston, Tracy Pondo, Jennifer Hudson Jain and Ruth Lynfield
Pediatrics 2016;138;
DOI: 10.1542/peds.2016-2013 originally published online November 29, 2016;
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/138/6/e20162013
Data Supplement at:
http://pediatrics.aappublications.org/content/suppl/2016/11/22/peds.2016-2013.DCSupplemental
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