TY - JOUR
T1 - Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies
AU - Stoll, Barbara J.
AU - Puopolo, Karen M.
AU - Hansen, Nellie I.
AU - Sánchez, Pablo J.
AU - Bell, Edward F.
AU - Carlo, Waldemar A.
AU - Cotten, C. Michael
AU - D'Angio, Carl T.
AU - Kazzi, S. Nadya J.
AU - Poindexter, Brenda B.
AU - Van Meurs, Krisa P.
AU - Hale, Ellen C.
AU - Collins, Monica V.
AU - Das, Abhik
AU - Baker, Carol J.
AU - Wyckoff, Myra H.
AU - Yoder, Bradley A.
AU - Watterberg, Kristi L.
AU - Walsh, Michele C.
AU - Devaskar, Uday
AU - Laptook, Abbot R.
AU - Sokol, Gregory M.
AU - Schrag, Stephanie J.
AU - Higgins, Rosemary D.
N1 - Funding Information:
reported receiving grants from the NIH during the conduct of the study. Ms Hansen reported receiving grants from the NICHD during the conduct of the study. Dr Sánchez reported receiving grants from the NICHD NRN and the Centers for Disease Control and Prevention (CDC) during the conduct of the study and grants from Merck & Co and MedImmune–AstraZeneca outside the submitted work. Dr Bell reported receiving grants from the NIH during the conduct of the study. Dr Carlo reported receiving personal fees and nonfinancial support from MEDNAX outside the submitted work. Dr D’Angio reported receiving grants from the NICHD during the conduct of the study. Ms Hale reported receiving grants from the NICHD during the conduct of the study. Ms Collins reported receiving grants from the NICHD during the conduct of the study. Dr Das reported receiving grants from the NICHD during the conduct of the study. Dr Baker reported receiving personal fees from Pfizer, Inc, outside the submitted work. Dr Wyckoff reported receiving grants from University of Texas Southwestern Medical School during the conduct of the study. Dr Yoder reported receiving grants from the NICHD during the conduct of the study. Dr Watterberg reported receiving grants from the NICHD during the conduct of the study. Dr Walsh reported receiving grants from the NICHD during the conduct of the study. No other disclosures were reported.
Funding Information:
Funding/Support: This study was supported by cooperative agreements UG1 HD27904, UG1 HD21364, UG1 HD27853, UG1 HD40492, UG1 HD27851, UG1 HD27856, UG1 HD68278, UG1 HD36790, UG1 HD27880, UG1 HD34216, UG1 HD68270, UG1 HD53109, UG1 HD53089, UG1 HD68244, UG1 HD68263, UG1 HD40689, UG1 HD21385, and UG1 HD87229 from the NICHD (infrastructure and study support to the NRN); grants UL1 TR1425, UL1 TR1117, UL1 TR454, UL1 TR1108, UL1 TR1085, UL1 TR442, UL1 TR1449, and UL1 TR42 from NCATS (infrastructure support to
PY - 2020/7
Y1 - 2020/7
N2 - Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P =.008). Conclusions and Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens..
AB - Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P =.008). Conclusions and Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens..
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U2 - 10.1001/jamapediatrics.2020.0593
DO - 10.1001/jamapediatrics.2020.0593
M3 - Article
C2 - 32364598
AN - SCOPUS:85084305257
VL - 174
JO - JAMA Pediatrics
JF - JAMA Pediatrics
SN - 2168-6203
IS - 7
M1 - e200593
ER -