Perfil clínico ­ epidemiológico de sepsis temprana en recién nacidos. Estudio observacional de centro único / Clinical-epidemiological profile of early sepsis in newborns. A single-center observational study

Introducción: La sepsis neonatal temprana se describe como un síndrome clínico que se caracteriza por signos y síntomas asociados a infección sistémica, se presenta en las primeras 72 horas posterior al nacimiento. El objetivo del presente estudio fue determinar el perfil clínico ­ epidemiológico de la sepsis neonatal temprana en una unidad de cuidados intensivos neonatales de un centro de referencia regional en Guayaquil-Ecuador. Métodos: El presente estudio observacional, realizado en el Hospital "Teodoro Maldonado Carbo" de enero del 2017 al diciembre del 2020 incluyó neonatos con sepsis neonatal temprana con muestra no probabilística. Las variables: edad, edad gestacional, sexo, vía de infección, presencia de infecciones de del tracto urinario, peso, genopatías, Apgar al 1er minuto, escala de Silverman, etapas clínicas, llenado capilar, gasto urinario, variables clínicas, de laboratorio, hemocultivo, organismo casal. El análisis es univariado, descriptivo con frecuencias y porcentajes. Resultados: Se incluyeron 278 pacientes con edad gestacio-nal promedio de 33 semanas, fueron 59.4% hombres. Los factores de riesgo materno fueron a IVU en el embarazo e infección transplacentaria. Entre los factores asociados al neonato son el bajo peso (56%), prematuridad (67%). La clínica más frecuente fue eutermia y taquipnea (54%). En el perfil de laboratorio la neu-tropenia predominó (49%), mientras que los agentes causales identificados Staphylococcus hominis 7%, Escherichia coli 4.3% y Klebsiella pneumoniae 4%. Conclusión: Se determinó la relación directa entre las características epidemiológicas y las etapas clínicas de la sepsis neonatal.

Introduction: Early neonatal sepsis is a clinical syndrome characterized by signs and symptoms associated with systemic infection; it occurs in the first 72 hours after birth. This study aimed to determine the clinical-epidemiological profile of early neonatal sepsis in a neonatal intensive care unit of a regional reference center in Guayaquil, Ecuador. Methods: The present observational study, carried out at the "Teodoro Maldonado Carbo" Hospital from January 2017 to December 2020, included neonates with early neonatal sepsis with a nonprobabilistic sample. The variables were age, gestational age, sex, route of infection, presence of urinary tract infections, weight, genopathies, Apgar at 1 minute, Silverman scale, clinical stages, capillary refill, urinary output, clinical and laboratory variables, haem culture, and causative organism. The analysis is univariate and descriptive with frequencies and percentages. Results: A total of 278 patients with a mean gestational age of 33 weeks were included, and 59.4% were men. Maternal risk factors were UTI in pregnancy and transplacental infection. Among the factors associated with the newborn were low weight (56%) and prematurity (67%). The most frequent symptoms were euthermia and tachypnea (54%). In the laboratory profile, neutropenia predominated (49%), while the causative agents were Staphylococcus hominis (7%), Escherichia coli (4.3%), and Klebsiella pneumoniae (4%). Conclusion: The direct relationship between the epidemiological characteristics and the clinical stages of neonatal sepsis was determined.

Adherencia a las recomendaciones de prevención de la sepsis neonatal temprana asociada a la colonización por Streptococcus agalactiae en una institución de referencia en Bogotá, Colombia, 2019 / Adherence to recommendations for preventing early neonatal sepsis associated with Streptococcus agalactiae colonization in a referral center in Bogotá, Colombia, 2019

RESUMEN Objetivos: Evaluar la adherencia a las recomendaciones de tamización para la prevención de la sepsis neonatal, describir la prevalencia de colonización por estreptococo del grupo B y los desenlaces perinatales asociados a la colonización por esta bacteria. Materiales y métodos: Estudio de cohorte retrospectiva que incluyó gestantes a término y sus recién nacidos, en una clínica universitaria privada de alta complejidad en Bogotá, entre el 1 de julio y el 31 de diciembre de 2019. Se evaluó la adherencia a la tamización y a la profilaxis antibiótica intraparto para las gestantes colonizadas con EGB, la prevalencia de colonización y los desenlaces perinatales adversos tempranos. Resultados: Se incluyeron 1.928 mujeres. La adherencia a la tamización fue de 68,0 % (IC 95 %: 66-70,1), a la administración de antibióticos intraparto de 87,9 % (IC 95 %: 87,8 -88), pero hubo uso no indicado de antibióticos en 14,7 % de mujeres para una adherencia final a profilaxis antibiótica de 86,3 %. La prevalencia de colonización por EGB fue 12,5 % (IC 95 %: 10,7-14,3), la incidencia de hospitalización neonatal fue de 27,5 % (IC 95 %: 16,3-33,7); no hubo casos de mortalidad ni sepsis neonatal temprana atribuibles al estado de tamización, colonización o profilaxis antibiótica para EGB. Conclusiones: Se requieren nuevos estudios en otras instituciones para determinar la adherencia a esta guía, en especial en aquellas regiones que atienden usuarias adscritas al régimen subsidiado, con cobertura a la población más vulnerable, así como nuevos estudios poblacionales de prevalencia de EGB y costo-efectividad de la estrategia de tamización universal en comparación con la profilaxis antibiótica basada en factores de riesgo.

ABSTRACT Objectives: To assess adherence to screening recommendations for the prevention of neonatal sepsis, and describe the prevalence of colonization by Group B streptococcus (GBS) as well as the perinatal outcomes associated with colonization by this bacterium. Material and methods: Retrospective cohort study that included pregnant women at term and their newborns, seen at a private high-complexity clinic in Bogota, between July 1 and December 31, 2019. Adherence to screening and intrapartum antibiotic prophylaxis in pregnant women colonized with group B streptococcus, as well as the prevalence of colonization and early adverse perinatal outcomes were assessed. Results: Overall, 1928 women were included. Adherence to screening was 68.0 % (95 % CI: 66-70.1) and 87.9 % to intrapartum antibiotic administration (95 % CI: 87.8-88); non-indicated use of antibiotics occurred in 14.7 % of the women, for 86.3 % final adherence to antibiotic prophylaxis. The prevalence of GBS colonization was 12.5 % (95 % CI: 10.7-14.3); the incidence of neonatal hospitalization was 27.5 % (95 % CI: 16.3-33.7). There were no cases of mortality or early neonatal sepsis attributable to screening status, colonization or prophylactic antibiotics for GBS. Conclusions: Additional studies in other centers are required in order to determine adherence to this guideline, particularly in those that receive users affiliated to the subsidized regime which covers the most vulnerable population. Also, new population studies of GBS prevalence and cost-effectiveness of universal screening compared to risk factor-based antibiotic prophylaxis are needed.

Sepsis neonatal precoz: recomendaciones para su abordaje en la práctica clínica / Early neonatal sepsis: recommendations for approach in clinical practice / Sepse neonatal precoce: recomendações para sua abordagem na prática clínica

La sepsis neonatal precoz se define como la que se manifiesta en las primeras 72 horas de vida. Es una importante causa de morbilidad y mortalidad neonatal. Su incidencia es inversamente proporcional a la edad gestacional. Los microorganismos considerados como frecuentes son Streptoccocus del grupo B, Escherichia coli y Listeria monocytogenes. El diagnóstico de sepsis precoz se basa principalmente en la presencia de factores de riesgo como la corioamnionitis y la edad gestacional. Los signos clínicos son inespecíficos y los exámenes paraclínicos disponibles actualmente, como los reactantes de fase aguda (proteína C reactiva y procalcitonia) tienen escaso valor predictivo positivo. Se realizó una revisión bibliográfica de las últimas publicaciones disponibles sobre sepsis neonatal precoz en recién nacidos, en cuanto a su sospecha, confirmación diagnóstica y tratamiento. A partir de las últimas publicaciones se confeccionó una guía para el manejo clínico de los recién nacidos con sospecha de sepsis precoz.

Early neonatal sepsis is defined as that type of sepsis with an onset within the first 72 hours of life and that is a major cause of neonatal morbidity and mortality. Its incidence is inversely proportional to its gestational age. Frequent microorganisms are group B Streptococcus, Escherichia coli and Listeria monocytogenes. Early sepsis diagnosis is mainly based on the presence of risk factors such as chorioamnionitis and gestational age. Clinical signs are non-specific and currently available paraclinical tests such as acute phase reactants (C-reactive protein and procalcitonin) have little positive predictive value. A bibliographic review of the suspicion, diagnostic confirmation and treatment on Early Neonatal Sepsis in newborns in the latest papers and guidelines were prepared for the clinical treatment of newborns with suspected early sepsis.

A sepse neonatal precoce é definida como aquela que se manifesta nas primeiras 72 horas de vida e que é uma das principais causas de morbidade e mortalidade neonatal. Sua incidência é inversamente proporcional à idade gestacional. Os microrganismos considerados frequentes são o Streptococcus grupo B, Escherichia coli e Listeria monocytogenes. O diagnóstico de sepse precoce baseia-se principalmente na presença de fatores de risco como a coioamnionite e a idade gestacional. Os sinais clínicos são inespecíficos e os testes para-clínicos atualmente disponíveis, como reagentes de fase aguda (proteína C-reativa e procalcitonia) têm pouco valor preditivo positivo. Fizemos uma revisão bibliográfica das últimas publicações disponíveis sobre sepse neonatal precoce em recém-nascidos em termos de suspeita e confirmação diagnóstica e tratamento. Com base nas últimas publicações, elaboramos um guia para o manejo clínico de recém-nascidos com suspeita de sepse precoce.

Sepsis precoz, osteoartritis y meningitis: a propósito de un caso clínico / Early sepsis, osteoarthritis and meningitis: a clinical case / Sepse precoce, osteoartrite e meningite: relato de caso

Se expone el caso de un recién nacido que desarrolló sepsis connatal precoz a Streptococcus agalactiae, con meningitis aguda supurada y osteoartritis de rodilla izquierda. Como factor de riesgo la madre no tenía realizado el exudado rectovaginal, pesquisa que detecta la colonización por estreptococo del grupo B (EGB). Se aisló el germen en hemocultivo y en líquido de punción articular. Recibió tratamiento antibiótico adecuado a la sensibilidad del microorganismo y según pauta de sepsis con meningitis, evolucionando favorablemente. En este trabajo se describe la epidemiología de la sepsis neonatal y los cambios ocurridos luego de la implementación de la profilaxis antibiótica en el preparto.

We hereby present the case of a newborn with early connatal sepsis due to Streptococcus agalactiae, with acute suppurative meningitis and left knee osteoarthritis. As a risk factor, the mother had not performed the rectus vaginal exudate screening that detects colonization by Group B Streptococcus (GBS). The germ was isolated in blood culture and in joint puncture fluid. The patient received germ-sensitive antibiotic treatment for meningitis sepsis and evolved favorably. This paper describes the epidemiology of neonatal sepsis and the changes that have occurred after the administration of the antibiotic prophylaxis during pregnancy.

Apresentamos o caso de um recém-nascido com sepse neonatal precoce por Streptococcus agalactiae, com meningite supurativa aguda e osteoartrite de joelho esquerdo. Como fator de risco, a mãe não realizou teste de exsudato vaginal do reto que detecta a colonização por estreptococos do grupo B (SGB). O germe foi isolado em hemocultura e líquido de punção articular. A paciente recebeu tratamento com antibióticos germinativos para padrão meningite sepse e evoluiu favoravelmente. Este artigo descreve a epidemiologia da sepse neonatal e as mudanças ocorridas após a administração da profilaxia antibiótica durante a gravidez.

Características epidemiológicas da mortalidade neonatal e infantil em uma regional de saúde / Epidemiological characteristics of neonatal and infant mortality in a health regional area

Objetivou-se analisar o perfil epidemiológico e as causas da mortalidade neonatal e infantil, em uma Regional de Saúde, de janeiro/2018 a agosto/2020. Trata-se de pesquisa exploratória, descritiva, transversal, retrospectivo, com abordagem quantitativa. A coleta de dados ocorreu em agosto de 2020, por meio de questionário elaborado pelas pesquisadoras, com base nas declarações de óbito disponibilizadas no Sistema de Informações de Mortalidade. O instrumento abordou as variáveis, sexo, raça, cor, idade da criança, idade materna, escolaridade materna, via de parto, idade gestacional, peso ao nascer, causa do óbito. Os dados foram submetidos à análise estatística descritiva e distribuição de frequência, por meio do Statistical Package for the Social Sciences (SPSS), versão 25.0. Constatou-se o predomínio de óbitos no sexo masculino (56,5%), de raça branca (87,8%), com equivalência entre extremo baixo peso e adequado (31,3%), com a principal causa de óbito por septicemia (13,9%). Quanto aos dados maternos, prevaleceram idade entre 21 e 30 anos de idade (45,2%) com gestação única (85,21%) e parto cesariano (65,2 %). Desses, 47,87% ocorreram no ano de 2018. Analisar os aspectos da mortalidade neonatal e infantil possibilita o planejamento e a readequação de ações no atendimento à saúde da criança, durante o período mais vulnerável e mais crítico dela, contribuindo, assim, para redução do número de óbitos.

This study analyzed the epidemiological profile and the causes of neonatal and infant mortality in a Health Regional Area between January 2018 and August 2020. This is an exploratory, descriptive, cross-sectional, retrospective study with a quantitative approach. Data collection took place during August 2020 through a questionnaire prepared by the researchers, based on the death certificates available in the Mortality Information System. The instrument included the variables of sex, race, color, child's age, mother's age, maternal education, childbirth mode, gestational age, birth weight, cause of death. The data were submitted to descriptive statistical analysis and frequency distribution using the Statistical Package for the Social Sciences (SPSS) version 25.0. There was a predominance of deaths among boys (56.5%), Caucasian (87.8%), with equivalence between extreme low and adequate weight (31.3%), with the main cause of death being septicemia (13.9%). As for maternal data, age between 21 to 30 years old (45.2%) prevailed, and 85.21% had a single pregnancy, with C-section childbirth (65.2%). From these, 47.87% occurred in 2018. It can be concluded that analyzing the aspects of neonatal and child mortality enables the planning and adjustment of actions in child health care during its most vulnerable and most critical period, thus contributing to reducing the number of deaths.

Etiología y perfil de susceptibilidad antimicrobiana en sepsis neonatal / Etiology and antimicrobial susceptibility profile in neonatal sepsis

La sepsis neonatal es una importante causa de morbimortalidad. Se realizó un proceso investiga-tivo con el objetivo de describir la etiología y el patrón de susceptibilidad antimicrobiana de las bacterias aisladas más frecuentemente de los hemocultivos de neonatos con sepsis en el servicio de neonatología del Hospital General Docente de Ambato. La metodología empleada en esta investigación se basó en un estudio descriptivo, transversal y enfoque cuali-cuantitativo, empleando la técnica documental y el reporte de resultados como instrumento. De los 39 pacien-tes estudiados 64,10% fueron del género masculino. El 23,07% presentaron bajo peso y 33,33% una edad gestacional <37 semanas. El microorganismo más frecuente fue Staphylococcus epidermidis (51,28%) seguido de Escherichia coli (17,94%) y Staphylococcus aureus (15,38%). En relación al perfil de susceptibilidad antimicrobiana S. epidermidis y S. aureus se mostraron sensibles a linezolid y vancomicina en más del 80,00%, y presentaron alta resistencia a oxacilina (80,00 y 83,33%, respectivamente), estas cepas expresaron fenotípicamente el gen mecA. Las enterobacterias aisladas mostraron resistencia a amoxacilina/ácido clavulánico (61,53%), ampi-cilina/sulbactam (69,23%), ciprofloxacina (61,53%), ceftazidima (30,76%) y cefotaxima (38,46%). Además, cinco cepas de E. coli y Klebsiella pneumoniae eran fenotípicamente productoras de beta lactamasas de espectro extendido. En conclusión, es necesario realizar estu-dios locales de vigilancia microbiológica en los hospitales, con el fin de identificar los patógenos multirresistentes involucrados en las infecciones neonatales, reconocer los brotes y monitorizar los cambios que ocurren a través del tiempo; los cuales influyen finalmente, en la elección de los tratamientos empíricos.

Neonatal sepsis is a major cause of morbidity and mortality. The investigative process was carried out to describe the etiology and antimicrobial susceptibility pattern of the bacteria most frequently isolated from blood cultures of neonates with sepsis in the neonatology service of the Ambato General Teaching Hospital. The methodology used in this research was based on a descriptive, cross-sectional study and a quali-quantitative approach, using the documentary technique and the report of results as an instrument. 39 patients were studied, 64.10% of them were male. 23.07% had low weight and 33.33% had a gestational age <37 weeks. The most frequent microorganism was Staphylococcus epidermidis (51.28%), followed by Escherichia coli (17.94%) and Staphylococcus aureus (15.38%). In relation to the antimicrobial susceptibili-ty profile, S. epidermidis and S. aureus were sensitive to linezolid and vancomycin in more than 80.00% and presented high resistance to oxacillin (80.00 and 83.33%, respectively), these strains phenotypically expressed the mecA gene. Isolated Enterobacteriaceae showed resistance to amoxacillin / clavulanic acid (61.53%), ampicillin / sulbactam (69.23%), ciprofloxacin (61.53%), ceftazidime (30.76%) and cefotaxime (38.46%). Furthermore, five strains of E. coliand Klebsiella pneumoniae were phenotypically producers of extended spectrum beta lactama-ses. In conclusion, it is necessary to perform local microbiological surveillance studies in hospi-tals in order to identify multi-resistant pathogens involved in neonatal infections, recognize outbreaks and monitor the changes that occur over time, which influence the choice of empirical treatments.

Metabolomic changes of neonatal sepsis: an exploratory clinical study / 中国当代儿科杂志

OBJECTIVES@#To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission.@*METHODS@#A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points.@*RESULTS@#On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism.@*CONCLUSIONS@#The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

Effect of intrapartum antibiotic prophylaxis of group B streptococcus infection on the incidence and bacteriological profile of early-onset neonatal sepsis / 中国当代儿科杂志

OBJECTIVES@#To study the effect of intrapartum antibiotic prophylaxis (IAP) of group B streptococcus (GBS) infection on the incidence and bacteriological profile of early-onset neonatal sepsis (EONS).@*METHODS@#A retrospective analysis was performed on the medical data of 494 pregnant women with positive GBS screening results and 526 neonates born by these women. According to whether the pregnant woman received IAP, the neonates were divided into two groups: IAP (n=304) and control (n=222). The two groups were compared in terms of clinical indices, incidence rate of EONS, and distribution of pathogenic bacteria in blood culture.@*RESULTS@#Compared with the control group, the IAP group had a significantly lower proportion of children with abnormal clinical manifestations (P<0.001) and a significantly lower incidence rate of EONS (P=0.022). In the IAP group, Escherichia coli (2.3%) was the most common type of pathogenic bacteria in blood culture of the neonates with EONS, while GBS (3.2%) was the most common type of pathogenic bacteria in the control group. The IAP group had a significantly higher detection rate of ampicillin-resistant Escherichia coli than the control group (P=0.029).@*CONCLUSIONS@#Although IAP can significantly reduce the incidence rate of EONS in neonates born to pregnant women with positive GBS screening results, the infection rate of ampicillin-resistant Escherichia coli may increase after IAP treatment. Therefore, it is needed to enhance the monitoring of blood culture results of neonates with EONS and timely adjust treatment plan according to drug susceptibility test results.

Neonatal morbidity and mortality: A 5-year analysis at federal medical centre, Gusau, Zamfara State, Northwest Nigeria

OBJECTIVES: Neonatal morbidity and mortality have remained embarrassingly high in Nigeria compared to some countries in Sub-Saharan Africa. Nigeria ranked first in the burden of neonatal deaths in Africa. Therefore, there is need to know causes of newborn diseases and deaths in our neonatal unit. The objective of the study was to describe the morbidity and mortality of newborns admitted into Special Care Baby Unit of Federal Medical Centre, Gusau, Nigeria over a 5-year period. MATERIAL AND METHODS: This is a retrospective study covering January 2012 to December 2016. The case folders of all newborns admitted during this period were retrieved and the following information were extracted: Sex of babies, diagnoses, outcome in terms of discharges, deaths, referrals, and discharge against medical advice (DAMA). RESULTS: A total of 3,553 neonates were admitted during the period under review. The sex ratio for males and females was 1.4:1, respectively. The major diagnoses were neonatal sepsis (NNS) 36.5%, birth asphyxia 25.6%, and prematurity 16.1%. Mortality rate was 6.6% with major contributions from birth asphyxia (35.6%), prematurity (28.1%), and NNS (12.0%). DAMA rate was 1.7%. CONCLUSION: This study has shown that NNS, birth asphyxia, and prematurity are the dominant causes of morbidity and mortality. These are largely preventable.

Evaluation of serum and salivary C-reactive protein for diagnosis of late-onset neonatal sepsis: A single center cross-sectional study

Abstract Objective: To evaluate the diagnostic utility of salivary C-reactive protein (CRP) and its potential correlation with serum CRP levels in full-term neonates with late-onset sepsis (LOS). Methods: This cross-sectional study included 90 neonates assigned to three equal groups: culture proven LOS, clinical LOS and a control group. Clinical findings and routine laboratory data including complete blood pictures and blood culture results were documented. Highly sensitive serum CRP was measured according to hospital protocol, while salivary CRP levels were measured using enzyme-linked immunosorbent assay. Results: The median serum CRP was significantly higher in septic neonates compared to controls (p < 0.001). For serum CRP, the optimum cut-off value for LOS diagnosis was found to be 7.2 mg/L with sensitivity, specificity, positive and negative predictive values of 91, 100, 100, and 85.7%, respectively. No significant difference was observed in levels of salivary CRP among the 3 study groups (p = 0.39). No correlation was found between the levels of salivary and serum CRP (r = 0.074, p = 0.49). Conclusion: Serum CRP, at a cut-off value of 7.2 mg/L, exhibited a high specificity and positive predictive value in LOS diagnosis, whereas salivary CRP levels weren't significantly different between the 3 study groups nor did they predict abnormal serum CRP thresholds in newborns with sepsis.

Infección grave por estreptococo del grupo B en la Unidad de Cuidados Intensivos Pediátricos del Centro Hospitalario Pereira Rossell entre los años 2007 y 2017 / Serious infection due to group B Streptococcus at the Pediatric Intensive Care Unit of the Pereira Rossell Children's Hospital between 2007 and 2017 / Infecção grave causada por Estreptococo do grupo B na Unidade de Terapia Intensiva do Centro Hospitalar Pediátrico Pereira Rossell entre os anos 2007 e 2017

Introducción: el estreptococo del grupo B (EGB) es una causa frecuente de sepsis neonatal. La enfermedad precoz disminuyó su incidencia por la profilaxis antibiótica, a diferencia de la sepsis tardía, que aumentó su incidencia en los últimos años. Objetivo: conocer la incidencia de la sepsis tardía en el período 2016-2017 en el Centro Hospitalario Pereira Rossell (CHPR). El secundario, describir las características epidemiológicas y clínicas de sepsis tardía por EGB en niños ingresados a la Unidad de Cuidados Intensivos de Niños (UCIN) del CHPR en el período 2007-2017. Resultados: la incidencia calculada de sepsis tardía por EGB fue de 0,53 casos/1000 recién nacidos (RN) vivos. Entre los años 2007 y 2017 ingresaron cinco niños por sepsis tardía por EGB a la UCIN del CHPR. La presentación clínica más frecuentes fue fiebre sin foco y meningitis. Se obtuvieron tres aislamientos en sangre de EBG y tres en líquido cefalorraquídeo (dos en cultivo y otro por detección de ADN). Ninguno falleció. Los casos con meningitis presentaron alteraciones en la tomografía de cráneo. Un niño fue pretérmino. Conclusiones: la sepsis tardía se vincula a importante morbimortalidad en pediatría. No se ha establecido cuáles son los principales factores de riesgo asociados a una enfermedad grave ni las políticas para disminuir su incidencia.

Background: group B streptococcus (GBS) is a common cause of neonatal sepsis. Early disease decreased its incidence due to antibiotic prophylaxis. Late sepsis increased its incidence in recent years. Objectives: to know the incidence of late onset EGB sepsis in the period 2016-2017 at the Pereira Rossell Hospital Center (CHPR), and secondly, to describe the epidemiological characteristics and the clinical presentation of late onset sepsis due to GBS in children admitted to the Children's Intensive Care Unit (UCIN) of the CHPR in the period 2007-2017. Results: the calculated incidence of late sepsis due to GBS was 0.53 cases/1000 live newborns. Between 2007-2017, 5 children were admitted due to GBS late sepsis at the UCIN. The most frequent clinical presentation was fever without focus and meningitis. 3 isolates were obtained in EBG blood cultures and 3 in cerebrospinal fluid (2 in culture and another by DNA detection). None of them died. Cases with meningitis showed abnormalities in the brain tomography. 1 of the 5 was preterm. Conclusions: late sepsis is associated with significant morbidity and mortality in pediatric patients. The main risk factors associated with serious disease and the policies needed to reduce its incidence have not been established.

Introdução: o estreptococo do grupo B (SGB) é uma causa frequente de sepse neonatal. A doença precoce diminuiu sua incidência devido à profilaxia antibiótica, ao contrário da sepse tardia, que aumentou sua incidência nos últimos anos. Objetivo: conhecer a incidência de sepse tardia no período 2016-2017 no Centro Hospitalar Pereira Rossell (CHPR) e descrever as características epidemiológicas e clínicas da sepse tardia por SGB em crianças internadas na Unidade de Terapia Intensiva Infantil (UTIN) do CHPR no período de 2007-2017. Resultados: a incidência calculada de sepse tardia por SGB foi de 0,53 casos/1000 recém-nascidos vivos (RNs). Entre 2007-2017, 5 crianças foram internadas na UTIN do CHPR por sepse tardia devido a GBS. A apresentação clínica mais frequente foi febre sem causa e meningite. 3 isolados de EBG foram obtidos no sangue e 3 no líquido cefalorraquidiano (2 em cultura e outro por detecção de DNA). Nenhum dos pacientes morreu. Os casos com meningite apresentaram alterações na tomografia de crânio. Uma criança era pré-termo. Conclusões: a sepse tardia está associada a significativa morbimortalidade em pediatria. Os principais fatores de risco associados a uma doença grave e as políticas para reduzir sua incidência ainda não foram estabelecidas.

Infecciones intrahospitalarias por estafilococo coagulasa negativo en una unidad de neonatología / Coagulase negative streptococci nosocomial infections at a neonatal intensive care unit / Infecções intra-hospitalares por estafilococo coagulasa negativa numa unidade de neonatologia

Introducción: la sepsis tardía por estafilococo coagulasa negativo (SCoN) es una causa común de morbimortalidad en la unidad neonatal. Los SCoN son los microorganismos más frecuentemente involucrados con aproximadamente el 50% de los casos. El objetivo de este estudio es analizar la incidencia y las características de los neonatos portadores de sepsis tardía por SCoN. Materiales y métodos: se realizó un estudio descriptivo, longitudinal, retrospectivo. Se utilizaron las bases de datos del laboratorio de microbiología del hospital y las historias clínicas electrónicas para obtener la información. El período de estudio analizado fueron los años 2018 y 2019 en la unidad de cuidados intensivos e intermedios de recién nacidos del Centro Hospitalario Pereira Rossell. Resultados: obtuvimos una incidencia de 2,5% de los ingresos a cuidados intensivos e intermedios (25 pacientes). La edad gestacional al nacer fue de 28 semanas (25,0-35,0) y la mediana del peso fue de 1.070 g (730,0-2.365,0). La media de edad gestacional posmenstrual al momento del diagnóstico fue de 32,92±7,921 semanas. Por sospecha de sepsis precoz, 17 pacientes habían recibido un curso de antibióticos previo. El signo clínico más frecuentemente observado fue el deterioro del estado general, en 11 pacientes, seguido de distensión abdominal en 6 y fiebre en 5. Dentro de los SCoN, el más frecuentemente aislado fue el Staphylococcus epidermidis (13 pacientes); 22 pacientes recibieron tratamiento, 18 de ellos con vancomicina-meropenem y 4 con monoterapia con vancomicina. Conclusión: estos patógenos representan una causa importante de morbimortalidad en la unidad neonatal, particularmente en pacientes que presentan mayor gravedad y mayor necesidad de soporte vital. Se necesitan pautas claras de interpretación del rol de estos microorganismos y de abordaje de pacientes con riesgo de sepsis tardía, incluyendo el tratamiento antibiótico empírico.

Introduction: Coagulase Negative Staphylococci (CoNS) late onset sepsis is a common cause of morbidity and mortality in the neonatal intensive care unit (NICU). CoNS are the most frequently isolated microorganisms and total 50% of cases. The objective of this study is to analyze the incidence and characteristics of newborns carriers of late onset CoNS. Materials and methods: we performed a descriptive, retrospective, longitudinal study. Data was obtained from the hospital's microbiology laboratory database and electronic medical records. Patients included were those admitted to NICU during the period between 2018 and 2019. Results: we obtained an incidence of 2.5% of patients admitted to the NICU (25 patients). Median gestational age at birth was 28 weeks 25.0-35.0 and median birth weight was 1.070 g 730.0-2365.0. Mean gestational age at the time of diagnosis was 32.92±7.921 weeks. 17 patients had received an antibiotics course at birth because of early onset sepsis suspicion. The most frequently observed clinical symptom was deterioration of general condition, 11 patients, followed by abdominal distention in 6 and fever in 5. Among CoNS, the most frequently isolated pathogen was Staphylococcus epidermidis (13 patients). 22 patients received treatment, 18 a combination of vancomycin and meropenem and 4 received vancomycin monotherapy. Conclusion: these pathogens are a common cause of morbidity and mortality in the newborn intensive care unit, particularly in patients with more serious conditions and in those who require more advanced life support measures. Clearer interpretation of their role is needed as well as to determine a proper approach to patients at risk of late onset sepsis, including empiric antibiotic treatment.

Sepse tardia para Staphylococcus coagulase negativa (SCoN) é uma causa comum de morbidade e mortalidade na unidade neonatal. SCoNs são os microrganismos mais frequentemente envolvidos e representam aproximadamente 50% dos casos. O objetivo deste estudo é analisar a incidência e as características de neonatos com sepse tardia por SCoN. Materiais e métodos: foi realizado um estudo descritivo, longitudinal e retrospectivo. Usamos os bancos de dados do laboratório de microbiologia e prontuários médicos eletrônicos de nosso hospital para obter as informações. O período de estudo analisado foi de 2018 e 2019 na unidade de terapia intensiva e intermediária para recém-nascidos do Centro Hospitalar Pereira Rossell. Resultados: obtivemos uma incidência de 2,5% de internações em Terapia Intensiva e Intermediária (25 pacientes). A idade gestacional ao nascer foi de 28 semanas 25,0-35,0 e o peso médio foi de 1070g 730,0-2365,0. A média da idade gestacional pós-menstrual no momento do diagnóstico foi de 32,92 ± 7,921 semanas. 17 pacientes haviam recebido um curso anterior de antibióticos por suspeita de sepse precoce. O sinal clínico mais frequentemente observado foi deterioração do estado geral em 11 pacientes, seguido por distensão abdominal em 6 e febre em 5. Dentre os SCoN, o mais isolado foi o Staphylococcus Epidermidis (13 pacientes). 22 pacientes receberam tratamento, 18 deles com Vancomicina-Meropenem e 4 com Vancomicina em monoterapia. Conclusão: esses patógenos representam uma importante causa de morbimortalidade na unidade neonatal, principalmente em pacientes com maior gravidade e maior necessidade de suporte de vida. Orientações claras são necessárias para interpretar o papel desses microrganismos e para abordar pacientes com risco de sepse tardia, incluindo tratamento com antibióticos.

Medicina de precisión para el diagnóstico de sepsis neonatal: revisión sistemática y metaanálisis / Precision medicine for the diagnosis of neonatal sepsis: systematic review and meta-analysis

ANTECEDENTES: Los biomarcadores actuales para el diagnóstico de sepsis neonatal tienen una exactitud limitada. El desarrollo de la medicina de precisión basada en tecnologías ómicas ofrece una oportunidad para mejorar el diagnóstico de la sepsis neonatal. OBJETIVOS: Evaluar la sensibilidad y especificidad de las pruebas basadas en tecnologías ómicas (metabolómica, proteómica y genómica/transcriptómica) para el diagnóstico de sepsis neonatal. METODOLOGÍA: Se realizó una revisión sistemática en bases de datos electrónicas. Se incluyeron estudios observacionales y ensayos clínicos que evaluaran las pruebas basadas en tecnologías ómicas en neonatos comparado con el cultivo para el diagnóstico de sepsis neonatal. Dos revisores independientes realizaron la evaluación de la calidad de los estudios y la extracción de los datos. Para el metaanálisis se realizó un modelo de efectos aleatorios y se planeó una evaluación de la heterogeneidad a través de un análisis de subgrupos por prueba ómica, edad gestacional y tiempo de establecimiento de la sepsis. RESULTADOS: Se observa expresión diferencial del genoma, proteoma y metaboloma entre los neonatos con y sin sepsis, identificando diferentes biomarcadores. El metaanálisis mostró una medida de resumen combinada para la sensibilidad de 0,88 (IC 95% 0,72-0,96), especificidad de 0,76 (IC 95% 0,62-0,85). CONCLUSIÓN: Las pruebas basadas en ómicas tienen una alta sensibilidad, siendo las de mejor rendimiento las basadas en genómica/transcriptómica. Los estudios tienen alta heterogeneidad.

BACKGROUND: Current biomarkers for the diagnosis of neonatal sepsis llave limited accuracy. The development of precision medicine based on omic's technologies offer an opportunity to improve the diagnosis of neonatal sepsis. AIM: To evalúate the sensitivity and specificity of tests based on omic technologies (metabolomics, proteomics and genomics) for the diagnosis of neonatal sepsis. METHODS: A systematic review was carried out in electronic databases. Observational studies and clinical trials evaluating tests based on omic technologies in neonates compared to culture for the diagnosis of neonatal sepsis were included. For the meta-analysis, a random effects model and an evaluation of heterogeneity were proposed through a subgroup analysis by omic test, gestational age and time of establishment of sepsis. RESULTS: Differential expression of the genome, proteome and metabolome is observed between neonates with and without sepsis, identifying different biomarkers. The meta-analysis showed a pooled summary measure for sensitivity of0.88 (95% CI 0.72, 0.96), specificity of0.76 (95% CI 0.62, 0.85). CONCLUSION: Omics-based tests have a high sensitivity, with the best performing ones being those based on genomics / transcriptomics. The studies have high heterogeneity.

Incidência de Streptococcus ß-Hemolítico em Gestantes do Município de Campinas, São Paulo / ß-hemolytic Streptococcus incidence in pregnant women of Campinas Municipality, São Paulo

Objetivo: O objetivo deste estudo foi avaliar a incidência de Streptococcus ß-hemolítico em gestantes e a suscetibilidade aos antimicrobianos das pacientes colonizadas. Métodos: Para isso, foram analisadas 4.380 amostras de secreções vaginais e anais de gestantes, a partir de 35 semanas de gestação, atendidas em laboratório particular na cidade de Campinas, para detecção da presença de Streptococcus ß-hemolítico. Resultados: Foi encontrada uma prevalência de colonização nas gestantes analisadas de 12% (504/4380), sendo 293 (13%) vaginais e 211 (10%) anais. Das positivas, foi realizado o perfil de resistência bacteriana em 60 amostras, sendo 20% das amostras anais resistentes à clindamicina e 22% à eritromicina e das amostras vaginais 25% resistentes à clindamicina e 33% à eritromicina, não havendo resistência à penicilina e ampicilina. Conclusão: Diante da incidência apresentada, ressalta-se a importância da realização do rastreio da colonização transitória de estreptococos ß-hemolíticos em gestantes durante o pré-natal, associado à adequada profilaxia intraparto, para minimizar os riscos de ocorrência de sepse nos neonatos.

Objective: The aim of this study was evaluate the incidence of ß-hemolytic Streptococcus in pregnant women and antimicrobial susceptibility of colonized patients. Methods: For this, a cohort of 4,380 of pregnant women, from 35 weeks of gestation, were analyzed, samples of vaginal and anal secretion were collected in a private laboratory in the city of Campinas. Result: The prevalence of colonization was of 12% (504/4380) in pregnant women was evidenced, being 293 (13%) vaginal and 211 (10%) anal. From the positives, the bacterial resistance profile was performed in 60 samples, 20% of the clinical samples resistant to Clindamycin and 22% of Erythromycin and 25% of the vaginal samples resistant to Clindamycin and 33% to Erythromycin, without resistance to Penicillin and Ampicillin. Conclusion: We conclude that the emphasize the importance of performing the screening of ß-hemolytic Streptococcus in pregnant women during the prenatal period, associated with adequate intrapartum prophylaxis is needed.

Fungemia por Malassezia sympodialis en una Unidad de Cuidados Intensivos Neonatal de Colombia / Fungemia by malassezia sympodialis in a neonatal intensive care unit in Colombia

Resumen El género Malassezia comprende levaduras lipofílicas, comensales de la piel de humanos y animales, responsables de infecciones dermatológicas y sistémicas, particularmente en recién nacidos pretérmino hospitalizados en Unidades de Cuidados Intensivos Neonatal (UCIN) con catéteres venosos centrales, antibióticos de amplio espectro y nutrición parenteral rica en lípidos. La información acerca de las fungemias por este microorganismo es limitada, sin embargo, la mayoría de infecciones invasivas reportadas en la literatura han sido asociadas con M. furfur y M. pachydermatis. Se reporta un caso de fungemia por M. sympodialis en un recién nacido pretérmino hospitalizado en la UCIN de un hospital colombiano con sospecha clínica de sepsis neonatal, antibioticoterapia de amplio espectro y hemocultivos de rutina negativos. El aislamiento fue susceptible a fluconazol y voriconazol, y resistente a anfotericina B. Existen pocos reportes de fungemia producida por M. sympodialis, pero todos concuerdan en que es una levadura subestimada en individuos con factores predisponentes.

Abstract The genus Malassezia comprises lipophilic yeasts, commensals of the skin of humans and animals, responsible for dermatological and systemic infections, particu larly in preterm infants hospitalized in Neonatal Intensive Care Units (NICU) with central venous catheters, broad-spectrum antibiotics and parenteral nutrition rich in lipids. Information about fungemia by this microorganism is limited, however, the majority of invasive infections reported in the literature have been associated with M. furfur and M. pachydermatis. A case of M. sympodialis fungemia is reported in a preterm newborn hospitalized in the NICU of a Colombian hospital with clinical suspicion of neonatal sepsis, broad-spectrum antibiotic therapy and negative routine blood cultures. The isolation was susceptible to fluconazole and voriconazole, and resistant to amphotericin B. There are few reports of fungemia produced by M. sympodialis, but all agree that it is an underestimated yeast in individuals with predisposing factors.

Utilidad de la proteína C-reactiva en la sepsis neonatal temprana / Utility of C-reactive protein in early neonatal sepsis

INTRODUCCIÓN: La baja sensibilidad y especificidad de las ayudas diagnósticas y el bajo aislamiento en los cultivos dificulta el reconocimiento de la sepsis bacteriana de inicio temprano en neonatos. OBJETIVO: Determinar la validez diagnóstica de la de la proteína C reactiva (PCR) en la sepsis en la sepsis neonatal temprana. MÉTODO: Se evaluó el papel de la PCR en el diagnóstico de sepsis neonatal temprana. Las concentraciones se midieron a las 12 y 48 h de vida en pacientes con sospecha de sepsis. Al evaluar la sensibilidad y especificidad de la PCR, se utilizó el resultado de manera cuantitativa y mediante una curva ROC no paramétrica se estimó sensibilidad y especificidad, razones de verosimilitud y porcentaje de clasificación correcta para cada punto de corte posible. RESULTADOS: El estudio incluyó 198 pacientes. La sensibilidad, especificidad, valor predictor positivo (VPP), valor predictor negativo (VPN), índice de probabilidad positiva e índice de probabilidad negativa de la PCR fue de 72,2 - 82,4 - 45,2 - 93,7 - 4,1 y 0,3, respectivamente con área bajo la curva de 0,78. CONCLUSIONES: La PCR es particularmente útil para descartar una infección. Dos PCR seriadas negativas en ausencia de expresión clínica y de hemocultivos positivos tienen un alto VPN y un índice de probabilidad negativa a favor de excluir la infección con una alta certeza y/o de descontinuar la terapia antibiótica.

BACKGROUND: The low sensitivity and specificity of diagnostic aids and the low isolation in cultures make it difficult to recognize early-onset bacterial sepsis in neonates. AIM: Determine the diagnostic validity of C reactive protein (CRP) in early neonatal sepsis. METHOD: The role of CRP in the diagnosis of early-onset neonatal sepsis was evaluated. Levels were measured at 12 and 48 hours of life in patients with suspected sepsis. When evaluating the sensitivity and specificity of the CRP, the result was used quantitatively, using a non-parametric ROC curve to estimate sensitivity and specificity, likelihood ratios and percentage of correct classification for each possible cut-off point. RESULTS: The study included 198 patients. The sensitivity, specificity, positive predictive value, negative predictive value, positive probability index and negative probability index of CRP, were 72.2 - 82.4 - 45.2 - 93.7 - 4.1, and 0.3, respectively with area under the curve of 0.78. CONCLUSIONS: CRP is particularly useful to rule out infection. Two negative serial CRP in the absence of clinical symptoms and positive blood cultures have a high negative predictive value and a negative probability index in favor of excluding infection with high certainty and/or discontinuing antibiotic therapy.

Costos directos de la infección adquirida en la comunidad en neonatos a término con bajo riesgo al nacer, Cundinamarca, Colombia / Direct costs of neonatal infection acquired in the community in full-term newborns and low risk at birth, Cundinamarca, Colombia

Resumen | Introducción. El 50 % de los episodios de sepsis neonatal se originan en la comunidad, con un gran porcentaje de mortalidad y complicaciones. Objetivo. Estimar los costos directos de la hospitalización por infección neonatal adquirida en la comunidad en neonatos a término con bajo riesgo al nacer. Materiales y métodos. Se utilizó la perspectiva del tercer pagador y la técnica de microcosteo; el horizonte de tiempo fue la duración de la hospitalización. La determinación de las situaciones generadoras de costos se obtuvo por medio de un consenso de expertos y se cuantificaron con base en la factura detallada de la atención de 337 neonatos hospitalizados. Los costos de los medicamentos se calcularon con base en el Sistema de Información de Precios de Medicamentos (SISMED) y, el de los procedimientos, según los manuales tarifarios ISS 2001 con porcentaje de ajuste y el seguro obligatorio de accidentes de tráfico (SOAT). Para incorporar la variabilidad de la información en la estimación, se obtuvo una distribución de los costos usando el método de bootstrapping. Resultados. Se incluyeron las facturas por la atención de 337 recién nacidos. El promedio de costos directos de la atención por paciente fue de COL$ 2'773.965 (desviación estándar, DE=$ 198.813,5; IC95%: $ 2'384.298 - $ 3'163.632). Las principales categorías generadoras de costos fueron la internación en la unidad de cuidados intensivos y las tecnologías en salud. Los costos siguieron una una distribución logarítmica normal (log-normal). Conclusiones. Las categorías con mayor impacto en los costos fueron la internación en la unidad neonatal y las tecnologías en salud. Los costos se ajustaron a una distribución logarítmica normal.

Abstract | Introduction: Half of the episodes of neonatal sepsis are acquired in the community with a high percentage of mortality and complications. Objective: To estimate the direct costs of hospitalizations due to systemic neonatal infection acquired in the community in low-risk newborns. Materials and methods: For the estimation of costs, we used the perspective of the health systems and the microcosting technique and we established the duration of hospitalization as the time horizon. We identified cost-generating events through expert consensus and the quantification was based on the detailed bill of 337 hospitalized newborns diagnosed with neonatal infection. The costs of the medications were calculated based on the drug price information system (SISMED) and the ISS 2001 rate manuals adjusting percentage, and the mandatory insurance rates for traffic accidents (SOAT). We used the bootstrapping method for cost distribution to incorporate data variability in the estimate. Results: We included the medical care invoices for 337 newborns. The average direct cost of care per patient was USD$ 2,773,965 (Standard Deviation, SD=USD$ 198,813.5; 95% CI: $ 2,384,298 - $ 3,163,632). The main cost-generating categories were hospitalization in intensive care units and health technologies. The costs followed a log-normal distribution. Conclusions: The categories generating the greatest impact on the care costs of newborns with infection were hospitalization in neonatal units and health technologies. The costs followed a log-normal distribution.

Diversity of the T cell receptor β chain complementarity-determining region 3 in peripheral blood of neonates with sepsis: an analysis based on immune repertoire sequencing / 中国当代儿科杂志

OBJECTIVES@#To investigate the diversity of peripheral blood T cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) based on immune repertoire sequencing in neonates with sepsis and the possible pathogenesis of neonatal sepsis.@*METHODS@#A total of 12 neonates with sepsis were enrolled as the case group, and 9 healthy full-term infants, matched for gestational age, birth weight, and age, were enrolled as the control group. Omega nucleic acid purification kit (SQ blood DNA Kit II) was used to extract DNA from peripheral blood samples, TCR β chain CDR3 was amplified by multiplex PCR, and then high-throughput sequencing was performed for the products to analyze the diversity of TCR β chain CDR3 and the difference in expression.@*RESULTS@#The length and type of TCR β chain CDR3 were similar between the case and control groups, and Gaussian distribution was observed in both groups. With D50 and Shannon-Wiener index as the evaluation indices for diversity, the case group had a significantly lower diversity of TCR β chain CDR3 than the control group (@*CONCLUSIONS@#There is a significant change in the diversity of TCR β chain CDR3 in the peripheral blood of neonates with sepsis, suggesting that it might be associated with the immune pathogenesis of neonatal sepsis.

miR-141 is negatively correlated with TLR4 in neonatal sepsis and regulates LPS-induced inflammatory responses in monocytes

Neonatal sepsis is an inflammatory system syndrome and a main cause of neonatal mortality. However, there is a lack of ideal biomarkers for early neonatal sepsis diagnosis. The aim of this study was to evaluate the clinical significance of miR-141 in sepsis in neonates, and explore the regulatory effects of miR-141 on inflammation in monocytes. This study used qRT-PCR to calculate the expression of miR-141 in the serum of septic neonates. The diagnostic values of procalcitonin (PCT) and serum miR-141 were evaluated by receiver operating characteristic (ROC) curves. The relationship between miR-141 and TLR4 was determined using luciferase reporter assay. An inflammation model was established using monocytes with lipopolysaccharide (LPS) treatment. ELISA assay was used to analyze the levels of pro-inflammatory cytokines. The expression of miR-141 in neonatal sepsis was significantly lower than healthy controls. ROC curves showed that miR-141 had diagnostic accuracy. LPS stimulation in monocytes led to a decrease in the expression of miR-141. A luciferase reporter assay proved that miR-141 targeted TLR4, and a negative correlation of miR-141 with TLR4 was found in septic neonates. ELISA results demonstrated that the overexpression of miR-141 inhibited LPS-induced inflammation in monocytes. In conclusion, serum decreased miR-141 expression served as a candidate diagnostic biomarker of neonatal sepsis. TLR4 is a target gene of miR-141, which may mediate the inhibitory effects of miR-141 overexpression on LPS-induced inflammation in monocytes. Therefore, miR-141 is expected to be a potential diagnostic biomarker and a therapeutic target in neonatal sepsis.