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OBJECTIVES: To determine performance of C-reactive protein (CRP) in the diagnosis of early-onset sepsis, and to assess patient outcomes with and without routine use of CRP. STUDY DESIGN: This was a retrospective cohort study of infants admitted to 2 neonatal intensive care units. CRP was used routinely in early-onset sepsis evaluations during 2009-2014; this period was used to determine CRP performance at a cut-off of ≥10 mg/L in diagnosis of culture-confirmed early-onset sepsis. Routine CRP use was discontinued during 2018-2020; outcomes among infants admitted during this period were compared with those in 2012-2014. RESULTS: From 2009 to 2014, 10â134 infants were admitted; 9103 (89.8%) had CRP and 7549 (74.5%) had blood culture obtained within 3 days of birth. CRP obtained ±4 hours from blood culture had a sensitivity of 41.7%, specificity 89.9%, and positive likelihood ratio 4.12 in diagnosis of early-onset sepsis. When obtained 24-72 hours after blood culture, sensitivity of CRP increased (89.5%), but specificity (55.7%) and positive likelihood ratio (2.02) decreased. Comparing the periods with (n = 4977) and without (n = 5135) routine use of CRP, we observed lower rates of early-onset sepsis evaluation (74.5% vs 50.5%), antibiotic initiation (65.0% vs 50.8%), and antibiotic prolongation in the absence of early-onset sepsis (17.3% vs 7.2%) in the later period. Rate and timing of early-onset sepsis detection, transfer to a greater level of care, and in-hospital mortality were not different between periods. CONCLUSIONS: CRP diagnostic performance was not sufficient to guide decision-making in early-onset sepsis. Discontinuation of routine CRP use was not associated with differences in patient outcomes despite lower rates of antibiotic administration.
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Proteína C-Reactiva , Sepsis , Recién Nacido , Humanos , Proteína C-Reactiva/análisis , Estudios Retrospectivos , Sepsis/tratamiento farmacológico , Antibacterianos/uso terapéutico , BiomarcadoresRESUMEN
Early-onset sepsis (EOS) is a significant cause of morbidity and mortality among newborn infants, particularly among those born premature. The epidemiology of EOS is changing over time. Here, we highlight the most contemporary data informing the epidemiology of neonatal EOS, including incidence, microbiology, risk factors, and associated outcomes, with a focus on infants born in high-income countries during their birth hospitalization. We discuss approaches to risk assessment for EOS, summarizing national guidelines and comparing key differences between approaches for term and preterm infants. Lastly, we analyze contemporary antibiotic resistance data for EOS pathogens to inform optimal empiric treatment for EOS.
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Enfermedades del Prematuro , Sepsis Neonatal , Sepsis , Lactante , Recién Nacido , Humanos , Sepsis Neonatal/diagnóstico , Sepsis Neonatal/tratamiento farmacológico , Sepsis Neonatal/epidemiología , Recien Nacido Prematuro , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/terapia , Farmacorresistencia MicrobianaRESUMEN
BACKGROUND: Empiric administration of ampicillin and gentamicin is recommended for newborns at risk of early-onset sepsis (EOS). There are limited data on antimicrobial susceptibility of all EOS pathogens. METHODS: Retrospective review of antimicrobial susceptibility data from a prospective EOS surveillance study of infants born ≥22 weeks' gestation and cared for in Neonatal Research Network centers April 2015-March 2017. Nonsusceptible was defined as intermediate or resistant on final result. RESULTS: We identified 239 pathogens (235 bacteria, 4 fungi) in 235 EOS cases among 217,480 live-born infants. Antimicrobial susceptibility data were available for 189/239 (79.1%) isolates. Among 81 Gram-positive isolates with ampicillin and gentamicin susceptibility data, all were susceptible in vitro to either ampicillin or gentamicin. Among Gram-negative isolates with ampicillin and gentamicin susceptibility data, 72/94 (76.6%) isolates were nonsusceptible to ampicillin, 8/94 (8.5%) were nonsusceptible to gentamicin, and 7/96 (7.3%) isolates were nonsusceptible to both. Five percent or less of tested Gram-negative isolates were nonsusceptible to each of third or fourth generation cephalosporins, piperacillin-tazobactam, and carbapenems. Overall, we estimated that 8% of EOS cases were caused by isolates nonsusceptible to both ampicillin and gentamicin; these were most likely to occur among preterm, very-low birth weight infants. CONCLUSIONS: The vast majority of contemporary EOS pathogens are susceptible to the combination of ampicillin and gentamicin. Clinicians may consider the addition of broader-spectrum therapy among newborns at highest risk of EOS, but we caution that neither the substitution nor the addition of 1 single antimicrobial agent is likely to provide adequate empiric therapy in all cases.
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Antiinfecciosos/uso terapéutico , Bacterias/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Sepsis Neonatal/tratamiento farmacológico , Ampicilina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Bacterias/aislamiento & purificación , Gentamicinas , Edad Gestacional , Humanos , Recién Nacido , Sepsis Neonatal/epidemiología , Sepsis Neonatal/microbiología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ~1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.
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Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important for determining SARS-CoV-2 exposures within both individuals and populations. We validated a SARS-CoV-2 spike receptor binding domain serological test using 834 pre-pandemic samples and 31 samples from COVID-19 recovered donors. We then completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate exposure to SARS-CoV-2 within the community.
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Anticuerpos Antivirales/sangre , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Disparidades en el Estado de Salud , Neumonía Viral/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Estudios de Cohortes , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Pandemias , Philadelphia/epidemiología , Neumonía Viral/sangre , Neumonía Viral/inmunología , Neumonía Viral/virología , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/virología , Dominios Proteicos/inmunología , SARS-CoV-2 , Estudios Seroepidemiológicos , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the hypothesis that early-onset sepsis increases risk of death or neurodevelopmental impairment (NDI) among preterm infants; and that among infants without early-onset sepsis, prolonged early antibiotics alters risk of death/NDI. STUDY DESIGN: Retrospective cohort study of infants born at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2014) at 22-26 weeks of gestation and birth weight 401-1000 g. Early-onset sepsis defined as growth of a pathogen from blood or cerebrospinal fluid culture ≤72 hours after birth. Prolonged early antibiotics was defined as antibiotics initiated ≤72 hours and continued ≥5 days without culture-confirmed infection, necrotizing enterocolitis, or spontaneous perforation. Primary outcome was death before follow-up or NDI assessed at 18-26 months corrected age. Poisson regression was used to estimate adjusted relative risk (aRR) and CI for early-onset sepsis outcomes. A propensity score for receiving prolonged antibiotics was derived from early clinical factors and used to match infants (1:1) with and without prolonged antibiotic exposure. Log binomial models were used to estimate aRR for outcomes in matched infants. RESULTS: Among 6565 infants, those with early-onset sepsis had higher aRR (95% CI) for death/NDI compared with infants managed with prolonged antibiotics (1.18 [1.06-1.32]) and to infants without prolonged antibiotics (1.23 [1.10-1.37]). Propensity score matching was achieved for 4362 infants. No significant difference in death/NDI (1.04 [0.98-1.11]) was observed with or without prolonged antibiotics among the matched cohort. CONCLUSIONS: Early-onset sepsis was associated with increased risk of death/NDI among extremely preterm infants. Among matched infants without culture-confirmed infection, prolonged early antibiotic administration was not associated with death/NDI.
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Antibacterianos/administración & dosificación , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Edad de Inicio , Preescolar , Estudios de Cohortes , Femenino , Humanos , Recien Nacido Extremadamente Prematuro , Masculino , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/etiología , Estudios Retrospectivos , Medición de Riesgo , Sepsis/complicaciones , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160002.
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Incubadoras para Lactantes/estadística & datos numéricos , Equipo Infantil/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Peso Corporal , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro/fisiología , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , MasculinoRESUMEN
OBJECTIVE: To examine the effect of separation for early-onset sepsis (EOS) evaluations due to perinatal risk factors on breastfeeding practices among asymptomatic term newborns. METHODS: This observational study included 692 nulliparous women with term, singleton uncomplicated pregnancies who intended to breastfeed and whose infants were well appearing at birth. We examined the rate of early breastfeeding initiation (within 2 hours of birth) and formula supplementation (in the first 24 hours) among this mother-infant cohort. RESULTS: Asymptomatic infants separated for EOS evaluation within 2 hours of birth were more likely to have delayed initiation of breastfeeding (46.5% vs 12.5%; P<.001). This association remained significant when adjusted for potential confounders (adjusted odds ratio [aOR]: 5.5 [95% confidence interval (CI): 3.4-8.9]; P<.001). Among infants separated for EOS evaluation, mother-infant time together of ≤0.5 hour in the first 2 hours of life significantly delayed initiation (aOR: 8.9 [95% CI: 1.5-53.7]; P=.02) compared with infants spending >1.5 hours with their mothers. In bivariate analysis, both separation and initiation were associated with formula supplementation. After adjusting for confounders, only delayed initiation remained significantly associated with supplementation (aOR: 1.9 [95% CI: 1.1-3.5]; P=.03). CONCLUSIONS: Early separation of asymptomatic infants from their mothers for EOS evaluation was significantly associated with delayed initiation of breastfeeding, which in turn was associated with increased formula supplementation in the first day of life. This unintended consequence of EOS evaluations among asymptomatic infants may be minimized by delaying early separation for performance of the evaluation, attempting breastfeeding initiation before separation, and/or applying more efficient criteria for identifying infants requiring evaluation.