Hydroxynonenal alleviates neonatal sepsis-induced acute lung injury by inhibiting endothelial cell pyrosis / 实用医学杂志

Objective To explore the role of 4-hydroxynonenal(HNE)in alleviating acute lung injury(ALI)induced by neonatal sepsis by inhibiting the focal death of endothelial cells(ECs).Methods Newborn mice were randomly divided into five groups:(1)Sham operation group(Sham group),(2)sham operation mice receiving HNE treatment group(Sham + HNE group),(3)cecal serosity(CS group),and(4)CS-treated GS-DMD-/-mice group(CS + GSDMD-/-group).The degree of lung injury was evaluated by lung histopathology and lung wet/dry weight ratio.The ECs of mice were isolated and divided into the Ctrl group,LPS + ATP group,LPS + ATP + HNE-L group and LPS + ATP + HNE-H group.Western blot was used to evaluate the expression of HNE and caspase-1 pathway.Results Compared with CS group,the lung tissue scores of CS + HNE group and CS + GSDMD-/-group were significantly decreased(P<0.05),and the ratio of wet to dry weight of lung tissues was significantly decreased(P<0.05).Compared with the CS group,the 72-hour survival rates of mice in the CS + HNE group and CS + GSDMD-/-group were significantly improved(P<0.05).The expressions of GSDMD-N,C-caspase-1,NLRP3,IL-18 and IL-1β in lung ECs of the CS + HNE group and CS + GSDMD-/-group were signifi-cantly lower than those of the CS group(P<005).Compared with the Ctrl cells,LPS + ATP significantly decreased the cell viability(P<0.05)and increased the protein expressions of GSDMD,C-caspase-1,NLRP3,IL-18 and IL-1β(P<0.05),and these effects were also inhibited by HNE.Conclusion HNE can inhibit the focal death of lung ECs cells by inhibiting NLRP3/caspase-1 signal transduction,and improve ALI in septic mice.

Early-onset neonatal sepsis as a risk factor for peri-intraventricular hemorrhage in premature infants / Sepse precoce como fator de risco para hemorragia peri-intraventricular em prematuros

ABSTRACT Objective: To assess early-onset sepsis as a risk factor of peri-intraventricular hemorrhage in premature infants born at less than or equal to 34 weeks' gestation and admitted to a neonatal intensive care unit (NICU). Methods: This retrospective cohort study included premature patients born at less than or equal to 34 weeks' gestation who were admitted to the NICU of a tertiary hospital in southern Brazil, and born from January 2017 to July 2021. Data were collected from patients' medical records. Early-onset sepsis was measured according to the presence or absence of diagnosis within the first 72 hours of life, whereas the outcome, peri-intraventricular hemorrhage, was described as the presence or absence of hemorrhage, regardless of its grade. Results: Hazard ratios were calculated using Cox regression models. A total of 487 patients were included in the study, of which 169 (34.7%) had some degree of peri-intraventricular hemorrhage. Early-onset sepsis was present in 41.6% of the cases of peri-intraventricular hemorrhage, which revealed a significant association between these variables, with increased risk of the outcome in the presence of sepsis. In the final multivariate model, the hazard ratio for early-onset sepsis was 1.52 (95% confidence interval 1.01-2.27). Conclusion: Early-onset sepsis and the use of surfactants showed to increase the occurrence of the outcome in premature children born at less than or equal to 34 weeks' gestation. Meanwhile, factors such as antenatal corticosteroids and gestational age closer to 34 weeks' gestations were found to reduce the risk of peri-intraventricular hemorrhage.

RESUMO Objetivo: O objetivo do presente trabalho foi avaliar a sepse precoce como fator de risco para hemorragia peri-intraventricular (HPIV) em prematuros com 34 semanas ou menos, admitidos em Unidade de Terapia Intensiva (UTI) Neonatal. Métodos: Este estudo de coorte retrospectivo incluiu pacientes prematuros com 34 semanas ou menos, que receberam alta da UTI Neonatal de hospital terciário, no sul do Brasil, nascidos no período de janeiro de 2017 a julho de 2021. Os dados foram coletados por meio dos prontuários desses pacientes. A sepse precoce foi mensurada conforme a presença ou a ausência do diagnóstico nas primeiras 72 horas de vida. Já o desfecho, hemorragia peri-intraventricular, foi descrito conforme a presença ou ausência da hemorragia, independentemente do grau. Resultados: Hazard ratios (HR) foram calculados por meio de modelos de regressão de Cox. Foram incluídos no estudo 487 pacientes. Destes, 169 (34,7%) apresentaram algum grau de hemorragia peri-intraventricular. A sepse precoce esteve presente em 41,6% dos casos de hemorragia peri-intraventricular e apresentou associação significativa, elevando o risco do desfecho quando presente. No modelo multivariável final, o HR para a sepse precoce foi de 1,52 (intervalo de confiança de 95% — IC95% 1,01-2,27). Conclusão: Sepse precoce e uso de surfactante demonstraram aumentar a ocorrência do desfecho em crianças prematuras até 34 semanas, enquanto fatores como corticoide antenatal e idades gestacionais mais próximas a 34 semanas mostraram reduzir o risco de ocorrência hemorragia peri-intraventricular.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation

Abstract Objective To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. Method Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. Results A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. Conclusions The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Prevalence of early neonatal sepsis and positive maternal culture for group B beta-hemolytic Streptococcus

SUMMARY OBJECTIVE: The aim of this study was to evaluate the prevalence of early neonatal sepsis in pregnant women with a positive culture for group B beta-hemolytic Streptococcus in a middle-income city in Southeastern Brazil. METHODS: A retrospective cohort study was conducted, involving singleton low- and high-risk pregnancies in whom group B beta-hemolytic Streptococcus cultures were evaluated between 35 and 37 weeks of gestation using vaginal and anal swabs. A specific medium (Todd-Hewitt) was used for culturing. The pregnant women were divided into two groups based on positive (n==201) and negative (n==420) cultures for group B beta-hemolytic Streptococcus. RESULTS: The maternal colonization rate by group B beta-hemolytic Streptococcus was 32.3%. The prevalence of early neonatal sepsis was 1.0% (2/201) among patients with a positive group B beta-hemolytic Streptococcus culture and 1.9% (8/420) among patients with a negative culture. Among the patients who underwent adequate prophylaxis, crystalline penicillin G was used in 51.9% (54/104), followed by cefazolin in 43.3% (45/104), ampicillin in 3.8% (4/104), and clindamycin in 1.0% (1/104). A model that included prematurity (p==0.001) proved to be an independent risk predictor of early neonatal sepsis [χ2 (1)==15.0, odds ratio: 16.9, 95% confidence interval: 4.7-61.6, p<0.001, Nagelkerke R2==0.157]. CONCLUSION: The prevalence of a positive culture for group B beta-hemolytic Streptococcus was high. However, the prevalence of early neonatal sepsis was low in pregnant women with both positive and negative group B beta-hemolytic Streptococcus cultures and in pregnant women with a positive culture who underwent both adequate and inadequate antibiotic prophylaxis. Prematurity proved to be an independent predictor of early neonatal sepsis, considering the entire study population.

Skin-to-skin contact and late-onset sepsis in newborns weighing up to 1.800g: a cohort study / Contato pele a pele e sepse tardia em recém-nascidos com peso até 1.800g: estudo de coorte

Abstract Objectives: to evaluate the association between the time to initiate the first skin-to-skin contact (SSC) and the daily practice time with the rates of late-onset sepsis in newborns ≤1,800g. Methods: a multicentric cohort study was carried out at the neonatal units located in three Brazilian geographic regions. The SSC time was recorded in individual files by the hospital staff and the newborn's parents. Maternal and neonatal data were obtained from medical records and through questionnaires applied to the mothers. Data analysis was carried out using a tree algorithm classification, which divided the data set into mutually exclusive subsets that best described the variable response. Results: 405 newborns participated in the study, with an average of 31.3 ± 2.7 weeks and 1,412g (QR=1,164-1,605g) as a median birth weight. The first SSC was carried out within 137 hours of life (≤5.7 days) was associated with a lower rate of late sepsis (p=0.02) for newborns who underwent daily SSC of 112.5 to 174.7 min/day (1.9 to 2.9h/day), with a reduction in the sepsis rate from 39.3% to 27.5%. Furthermore, the duration of SSC >174.7min/day (>2.9h/day) was relevant (p<0.001) for newborns who weighed >1,344g, with a reduction in this rate from 24.1% to 6%. Conclusions: SSP has been proven to be significant in reducing late-onset sepsis rates in preterm newborns, especially when carried out in a timely manner (≤5.7 days) and prolonged (>2.9h/day).

Resumo Objetivos: avaliar a associação entre o tempo para iniciar o primeiro contato pele a pele (CPP) e o tempo diário praticado com a taxa de sepse tardia em recém-nascidos ≤1.800g. Métodos: coorte multicêntrica realizada em unidades neonatais de três regiões geográficas brasileiras. O CPP foi registrado em ficha individual pela equipe e pais do recém-nascido. Dados maternos e neonatais foram obtidos por questionários aplicados às mães e em prontuários médicos. A análise dos dados foi realizada por algoritmo da árvore de classificação, que dividiu o conjunto de dados em subconjuntos mutuamente exclusivos que melhor descreveram a variável resposta. Resultados: 405 recém-nascidos participaram do estudo, com média de 31,3±2,7 semanas de idade gestacional e mediana de peso ao nascer 1.412g (IQ=1.164-1.605g). Realizar o primeiro CPP com até 137h de vida (≤5,7 dias) foi associado a menor taxa de sepse tardia (p=0,02) para recém-nascidos que fizeram CPP diário de 112,5 a 174,7 min/dia (1,9 a 2,9h/dia), com redução na taxa de sepse (39,3% para 27,5%). Além disso, a duração do CPP>174,7min/dia (>2,9h/dia) foi relevante (p<0,001) para os recém-nascidos >1.344g, com redução nesse desfecho (21,1% para 6%). Conclusões: o CPP mostrou-se importante para redução das taxas de sepse tardia em recém-nascidos pré-termo, especialmente quando realizado de forma oportuna (≤5,7 dias) e prolongada (>2,9h/dia).

A practical predictive model to predict 30-day mortality in neonatal sepsis

SUMMARY OBJECTIVE: Neonatal sepsis is a serious disease that needs timely and immediate medical attention. So far, there is no specific prognostic biomarkers or model for dependable predict outcomes in neonatal sepsis. The aim of this study was to establish a predictive model based on readily available laboratory data to assess 30-day mortality in neonatal sepsis. METHODS: Neonates with sepsis were recruited between January 2019 and December 2022. The admission information was obtained from the medical record retrospectively. Univariate or multivariate analysis was utilized to identify independent risk factors. The receiver operating characteristic curve was drawn to check the performance of the predictive model. RESULTS: A total of 195 patients were recruited. There was a big difference between the two groups in the levels of hemoglobin and prothrombin time. Multivariate analysis confirmed that hemoglobin>133 g/L (hazard ratio: 0.351, p=0.042) and prothrombin time >16.6 s (hazard ratio: 4.140, p=0.005) were independent risk markers of 30-day mortality. Based on these results, a predictive model with the highest area under the curve (0.756) was built. CONCLUSION: We established a predictive model that can objectively and accurately predict individualized risk of 30-day mortality. The predictive model should help clinicians to improve individual treatment, make clinical decisions, and guide follow-up management strategies.

Antibacterial activity of Nocardia spp. and Streptomyces sp. on multidrug-resistant pathogens causing neonatal sepsis

ABSTRACT Neonatal sepsis leads to severe morbidity and occasionally death among neonates within the first week following birth, particularly in low- and middle-income countries. Empirical therapy includes antibiotics recommended by WHO. However, these have been ineffective against antimicrobial multidrug-resistant bacterial strains such as Klebsiella spp, Escherichia coli, and Staphylococcus aureus species. To counter this problem, new molecules and alternative sources of compounds with antibacterial activity are sought as options. Actinobacteria, particularly pathogenic strains, have revealed a biotechnological potential still underexplored. This study aimed to determine the presence of biosynthetic gene clusters and the antimicrobial activity of actinobacterial strains isolated from clinical cases against multidrug-resistant bacteria implicated in neonatal sepsis. In total, 15 strains isolated from clinical cases of actinomycetoma were used. PCR screening for the PKS-I, PKS-II, NRPS-I, and NRPS-II biosynthetic systems determined their secondary metabolite-producing potential. The strains were subsequently assayed for antimicrobial activity by the perpendicular cross streak method against Escherichia fergusonii Sec 23, Klebsiella pneumoniae subsp. pneumoniae H1064, Klebsiella variicola H776, Klebsiella oxytoca H793, and Klebsiella pneumoniae subsp. ozaenae H7595, previously classified as multidrug-resistant. Finally, the strains were identified by 16S rRNA gene sequence analysis. It was found that 100% of the actinobacteria had biosynthetic systems. The most frequent biosynthetic system was NRPS-I (100%), and the most frequent combination was NRPS-I and PKS-II (27%). All 15 strains showed antimicrobial activity. The strain with the highest antimicrobial activity was Streptomyces albus 94.1572, as it inhibited the growth of the five multidrug-resistant bacteria evaluated.

Prevalencia de colonización rectovaginal por Streptococcus agalactiae en mujeres gestantes atendidas en un hospital de segundo nivel en Honduras

Introducción. Streptococcus agalactiae, conocido actualmente como estreptococo del grupo B (EGB), es el principal microorganismo que coloniza el tracto genitourinario en pacientes gestantes, llegando a causar consecuencias graves en el neonato, como sepsis neonatal, neumonía y meningitis. Objetivo. Determinar la prevalencia de EGB en mujeres gestantes del Hospital Nacional Dr. Mario Catarino Rivas, en Honduras. Materiales y métodos. Estudio descriptivo, prospectivo, transversal. Se utilizó un muestreo por conveniencia, se enroló un total de 143 gestantes entre las 34 y 40 semanas de gestación atendidas en el servicio de ginecología y obstetricia del Hospital Nacional Dr. Mario Catarino Rivas, durante enero de 2020 a junio del 2021. Los cultivos se prepararon de acuerdo con la metodología recomendada por los Centers for Disease Control and Prevention, agregándose el agar chromID Strepto B. Se empleó estadística descriptiva para el análisis. Resultados. La edad promedio de las gestantes fue 26 ± 7,4 años. La prevalencia de EGB en la población fue del 3,5%, encontrando 5 casos positivos. Conclusión. La prevalencia de colonización por EGB en mujeres embarazadas es variable y puede no estar asociada a factores de riesgo para ser colonizada, resultando en complicaciones sanitarias neonatales y maternas. Ello pone de manifiesto la necesidad de búsqueda activa de estreptococos del grupo B en las gestantes.

Introduction: Streptococcus agalactiae, currently known as group B streptococcus (GBS) is the main microorganism that colonizes the genitourinary tract in pregnant women, causing serious consequences in the neonate, such as neonatal sepsis, pneumonia, and meningitis. Objective: To determine the prevalence of GBS in pregnant women at the Dr. Mario Catarino Rivas National Hospital in Honduras. Materials and methods: Descriptive, prospective, cross-sectional study. A total of 143 pregnant women between 34-40 weeks of gestation attended at the gynecology and obstetrics service of the Dr. Mario Catarino Rivas National Hospital in Honduras from January 2020 to June 2021 were enrolled. Cultures were developed following the methodology recommended by the Centers for Disease Control and Prevention and Strepto B chromID agar was added. Descriptive statistics were used for analysis. Results: The mean age of the pregnant women was 26 ± 7.4 years. The prevalence of GBS in the study population was 3.5%, with 5 positive cases. Conclusion: The prevalence of GBS colonization in pregnant women is variable and may not be associated with risk factors for colonization, resulting in neonatal and maternal health complications. This highlights the need for active search for group B Streptococcus in pregnant women.

Prevalencia de sepsis neonatal confirmada microbiológicamente en una maternidad de la Ciudad Autó noma de Buenos Aires / Prevalence of microbiologically confirmed neonatal sepsis at a maternity center in the City of Buenos Aires

Introducción. En neonatos internados es frecuente sospechar sepsis neonatal, pero solo en el 25 % al 30 % se confirma con cultivos positivos. La selección del esquema antibiótico basándose en la epidemiología local favorece el uso racional y minimiza sus efectos colaterales. Objetivo primario. Describir la prevalencia de sepsis precoz y tardía con rescate microbiológico y sus características clínicas. Población y método. Estudio transversal retrospectivo, realizado del 1 de enero de 2013 al 31 de diciembre de 2017, en una maternidad pública de Argentina, que incluyó todos los recién nacidos internados en la unidad con diagnóstico de sepsis precoz y tardía con rescate microbiológico, y aquellos reingresados dentro del mes de vida. Resultados. Ingresaron 3322 recién nacidos, 1296 evaluados por sospecha de sepsis precoz, cultivos positivos en 25 (1,9 %; tasa: 0,86 ‰). El 52 % eran menores de 33 semanas de edad gestacional. Microorganismos: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Sepsis tardía (tasa 8,73 ‰), el 68 % ocurridas en menores de 33 semanas. Microorganismos intrahospitalarios: Staphylococcus coagulasa negativos 115, Staphylococcus aureus 47, Escherichia coli 30, Cándida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11 y Streptococcus agalactiae 10. En los reingresos: E. coli 11, S. aureus 12, SGB 3 y Haemophilus influenzae 3. Conclusiones. Se observa en el período estudiado una frecuencia de sepsis precoz similar a los reportes internacionales, con predominio de E. coli y L. monocytogenes. La tasa de sepsis tardía presentó una tendencia descendente en los años analizados, con predominio de los cocos grampositivos

Introduction. Neonatal sepsis is often suspected in hospitalized newborn infants, but only in 25­30% of cases it is confirmed via a positive culture. Selecting the antibiotics based on local epidemiology favors their rational use and minimizes their side effects. Primary objective. To describe the prevalence of early- and late-onset sepsis with microorganism isolation and their clinical characteristics. Population and method. Retrospective, cross-sectional study conducted between 01-01-2013 and 12-31-2017 in a public maternity center of Argentina in all hospitalized newborn infants with a diagnosis of early- and late-onset sepsis with microorganism isolation, and those re-admitted in their first month of life. Results. A total of 3322 newborn infants were admitted; 1296 were assessed for suspected early- onset sepsis; 25 had a positive culture (1.9%; rate: 0.86‰). Of these, 52% were born before 33 weeks of gestation. Microorganisms: Escherichia coli 5, Listeria monocytogenes 4, Streptococcus agalactiae (SGB) 3, Streptococcus pneumoniae 3. Also, 68% of late-onset sepsis cases (rate: 8.73‰) occurred in infants born before 33 weeks of gestation. Hospital-acquired microorganisms: coagulase-negative Staphylococcus 115, Staphylococcus aureus 47, Escherichia coli 30, Candida spp. 16, Enterococcus faecalis 13, Klebsiella pneumoniae 11, and Streptococcus agalactiae 10. In re-admissions: E. coli 11, S. aureus 12, SGB 3, and Haemophilus influenzae 3. Conclusions. During the study period, the frequency of early-onset sepsis was similar to international reports, with a predominance of E. coli and L. monocytogenes. The rate of late-onset sepsis showed a downward trend in the analyzed years, with a predominance of Gram-positive cocci.

Risk factors of acute kidney injury in very low birth weight infants in a tertiary neonatal intensive care unit

Abstract Objective Acute kidney injury (AKI) in the neonatal period is associated with worst outcomes as increased mortality and increased length of hospital stay. Very low birth weight (VLBW) newborns are at higher risk for developing several other conditions that are associated with worst outcomes. Understanding the risk factors for AKI may help to prevent this condition and improve neonatal care for this population. Methods This retrospective cohort study included 155 very low birth weight newborns admitted between 2015 and 2017. The authors compared the newborns who developed neonatal AKI with the non-AKI group and analyzed the main risk factors for developing AKI in the population. The authors also performed an analysis of the main outcomes defined as the duration of mechanical ventilation, length of stay, and death. Results From the cohort, a total of 61 (39.4%) patients had AKI. The main risk factors associated with Neonatal AKI were necrotizing enterocolitis (aOR 7.61 [1.69 - 34.37]; p = 0.008), neonatal sepsis (aOR 2.91 [1.17 - 7.24], p = 0.021), and hemodynamic instability (aOR 2.99 [1.35 - 6.64]; p = 0.007). Neonatal AKI was also associated with an increase in the duration of mechanical ventilation in 9.4 days (p = 0.026) and in an increase in mortality 4 times (p = 0.009), after adjusting for the other variables. Conclusion The present results highlight the importance of minimizing sepsis and necrotizing enterocolitis, as well as the importance of identifying hemodynamic instability, to prevent AKI and diminish the burden of morbimortality in VLBW newborns.

Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation

Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing ‘fit-for-use’ diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Three-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings.

Conservative management of newborns with 35 weeks or more of gestational age at risk for early-onset sepsis: a Brazilian cohort study

Abstract Objective: To evaluate the conservative management of newborns born at ≥35 weeks of gestational age, at risk for early-onset neonatal sepsis (EOS). Methods: Retrospective, analytic cohort study (2016 to 2019), including newborns ≥35 weeks of gestational at risk of EOS, asymptomatic at birth, managed conservatively in full rooming-in: serial physical examination and clinical observation for at least 48 h. They were classified into three groups, according to the clinical course: asymptomatic (group A), symptomatic for other reasons (group B), and with sepsis (group C). Risk factors, clinical signs and differential diagnoses of sepsis, length of stay, and discharge conditions were evaluated. Results: The authors evaluated 769 asymptomatic newborns at risk of EOS. (mean birth weight 2999 ± 485 g and gestational age 37.6 ± 1.7 weeks, respectively) corresponding to 12.2% of rooming-in admissions. The most prevalent risk factors were colonization by Group B Streptococcus (29%), prolonged rupture membrane duration (21.9%) and preterm labor (21.4%). Most of all of them (53.9%) remained asymptomatic (group A). Group B corresponded for 45.3%, and the most common clinical signs were hypothermia (24.5%), tremors (8.7%) and vomiting (8%). Environmental dysthermia (50.7%), prematurity (20.0%), and feeding intolerance (15.7%) were common in Group B. Laboratory tests were performed in 3.5%. Five patients (one confirmed) comprised group C (0.8/1,000 live births). There were no deaths. The median length of stay was 64 h (IQR 50-93). Conclusion: The rate of clinical/confirmed EOS was low. Most of the symptomatic patients only needed clinical evaluation to rule out sepsis. Management was shown to be safe.

Adherencia a la guía de práctica clínica de sepsis neonatal según tipo de sepsis en un Instituto Materno Perinatal de Lima, Perú / Adherence to neonatal sepsis clinical practice guideline according to type of sepsis in a Maternal Perinatal Institute of Lima, Peru

RESUMEN Objetivo: El objetivo de la presente investigación es describir adherencia a la guía de práctica clínica de sepsis neonatal según tipo de sepsis en un instituto materno perinatal de Lima, Perú. Método: Se elaboró un estudio descriptivo entre los meses de junio a diciembre del 2021 en el Instituto Nacional Materno Perinatal (INMP). Se evaluó la adherencia de las atenciones a la GPC de prevención, diagnóstico y tratamiento de sepsis neonatal basada en la evidencia del INMP. Las atenciones médicas fueron evaluadas por dos médicos quienes revisaron el cumplimiento o no de las 16 recomendaciones de la GPC enmarcadas en 6 dimensiones. Se consideró adherencia adecuada a un cumplimiento de 80% a más de las recomendaciones establecidos por la guía en una atención. Se calculó en porcentajes la adherencia global, por dimensiones, por ítem y según características maternas y perinatales de las atenciones. Resultados: Se evaluaron un total de 968 atenciones médicas de las cuales 553 fueron de casos de sepsis neonatal temprana y 435 de tardía. Para sepsis temprana se encontró una adherencia del 84.4% mientras que para sepsis tardía se encontró un 66.8%. El menor porcentaje de adherencia se encontró en las recomendaciones 2.7 y 3.2 de las atenciones de sepsis tardía. Conclusiones: Se encontró una adherencia adecuada en las atenciones de sepsis neonatal temprana, mientras que, en relación con la sepsis neonatal tardía, no se alcanzó un nivel de adherencia adecuado.

ABSTRACT Objective: The objective of this research is to describe adherence to the neonatal sepsis clinical practice guideline according to the type of sepsis in a perinatal maternal institute in Lima, Peru. Method: A descriptive study was carried out between the months of June to December 2021 at the Instituto Nacional Maternal Perinatal (INMP). The adherence of care to the CPG for the prevention, diagnosis and treatment of neonatal sepsis based on the INMP evidence was evaluated. Medical care was evaluated by two physicians who reviewed compliance or not with the 16 CPG recommendations. Adequate adherence was considered to be in compliance with 80% or more of the recommendations established by the guideline in one care. Global adherence was calculated in percentages, by dimensions, by item and according to maternal and perinatal characteristics of care. Results: A total of 968 medical attentions were evaluated, of which 553 were early neonatal sepsis cases and 435 late. For early sepsis, an adherence of 84.4% was found, while for late sepsis, 66.8% was found. The lowest percentage of adherence was found in recommendations 2.7 and 3.2 of late sepsis care. Conclusions: An adequate adherence was found in early neonatal sepsis care, while, in relation to late neonatal sepsis, an adequate level of adherence was not reached.

Sepsis neonatal: Diagnóstico y tratamiento

La sepsis neonatal es causa importante de morbilidad y mortalidad. La OMS reporta que anualmente mueren 2,4 millones de bebés durante el primer mes de vida, siendo la sepsis neonatal una de las principales causas. El objetivo es actualizar en el diagnóstico y tratamiento de la sepsis neonatal. En esta investigación se realizó una revisión de la literatura para sintetizar hallazgos relevantes sobre sepsis neonatal, que se define como afección sistémica, caracterizada por cambios hemodinámicos y otras manifestaciones clínicas, como respuesta desregulada a la infección. La sepsis neonatal precoz se relaciona con factores de riesgo maternos y los microorganismos causantes son del tracto genitourinario materno, mientras que la tardía es causada por gérmenes intrahospitalarios, en neonatos con estancia hospitalaria prolongada y sometidos a procedimientos invasivos. Los signos y síntomas de sepsis neonatal son inespecíficos, lo que hace difícil su diagnóstico, se recomienda identificar factores de riesgo y evaluación clínica minuciosa. Los establecimientos de salud deben realizar vigilancia epidemiológica de gérmenes más frecuentes y sensibilidad antibiótica, para garantizar tratamiento antibiótico adecuado.

Neonatal sepsis is a major cause of morbidity and mortality. The WHO reports that 2.4 million babies die annually during the first month of life, with neonatal sepsis being one of the main causes. The objective is to update the diagnosis and treatment of neonatal sepsis. In this research, a review of the literature was carried out to synthesize relevant findings on neonatal sepsis, which is defined as a systemic condition, characterized by hemodynamic changes and other clinical manifestations, as a deregulated response to infection. Early-onset neonatal sepsis is related to maternal risk factors and the causative microorganisms are from the maternal genitourinary tract, while late-onset sepsis is caused by nosocomial germs, in neonates with prolonged hospital stay and subjected to invasive procedures. The signs and symptoms of neonatal sepsis are nonspecific, which makes its diagnosis difficult, it is recommended to identify risk factors and a thorough clinical evaluation. Health establishments must carry out epidemiological surveillance of the most frequent germs and antibiotic sensitivity, to guarantee adequate antibiotic treatment.

Development and Validation of a Predictive Model for Neonatal Sepsis / 实用医学杂志

Objective To establish a Nomogram predictive model for Neonatal Sepsis(NS)based on the general characteristics and initial complete blood count of neonates.Methods Retrospective analysis was conducted on the clinical data of newborns who were admitted for the first time to NICU and completed blood routine examination after admission in the MIMIC Ⅲ database.The LASSO-Logistic regression was used to investigate the prediction factors of NS,and then Nomogram prediction model was established.Internal validation was performed using boot-strap resampling with 1000 iterations.External validation of the model was performed using the data from newborns admitted to the First Affiliated Hospital of Zhengzhou University.We evaluated the predictive performance by Area Under the Receiver Operating Characteristic Curve(AUROC),C-index,calibration curve,and decision curve analysis(DCA).Results Among the 3,001 neonates,185 were diagnosed with NS.The Nomogram model was con-structed based on indicators such as respiratory distress syndrome,gestational age,birthweight,and initial hemato-logical parameters(red blood cell count,white blood cell count,lymphocyte percentage,neutrophil percentage),exhibiting good predictive performance with an AUROC of 0.860.Satisfactory predictive abilities were confirmed through both internal and external validation.Conclusion This study developed and validated a well-performing Nomogram prediction model.With simple parameters,it can help clinicians identify newborns at high risk early.

Application value of procalcitonin in neonatal sepsis / 国际儿科学杂志

Procalcitonin(PCT), an important inflammatory suggestive marker of bacterial infection, has been widely used for the diagnosis of infectious diseases and guidance of antibiotic therapy in adults and children.Recent studies have shown that PCT, as a highly sensitive and specific inflammatory indicator, also has promising applications in the diagnosis and differential diagnosis, disease judgement, prognosis analysis, and antibiotic guidance of neonatal sepsis.Early PCT in neonates is characterized by physiological elevation, and it is important to understand the changing characteristics and influencing factors of PCT in neonates for an accurate clinical judgement of the disease.Therefore, we review the application value of PCT in neonatal sepsis.

Clinical analysis of different types of neonatal sepsis: a multi-center retrospective study / 中国新生儿科杂志

Objective:To study the clinical characteristics of different types of neonatal sepsis.Methods:From January 2012 to December 2019, neonates with confirmed sepsis from 5 neonatal centers of central-south China were reviewed. The neonates were assigned into early-onset sepsis (EOS) and late-onset sepsis (LOS) group, and the latter was further subgrouped into hospital-acquired LOS (hLOS) group and community-acquired LOS (cLOS) group. The etiological and clinical characteristics were analyzed. SPSS 26.0 was used for statistical analysis.Results:A total of 580 neonates were enrolled, including 286 (49.3%) in the EOS group and 294 (50.7%) in the LOS group. In LOS group, 147 were in hLOS group and 147 were in cLOS group. The gestational age and birth weight of hLOS group were significantly lower than the other two groups [(32.7±3.6) weeks vs. (37.1±3.7) weeks and (37.7±3.0) weeks, (1 810±717) g vs. (2 837±865) g and (3 024±710) g] ( P<0.05). The common pathogens in EOS and cLOS groups were coagulase-negative staphylococci and Escherichia coli, while Klebsiella pneumoniae was common in hLOS group. Carbapenems usage in the hLOS group was significantly higher than the other two groups [62.6% vs. 28.7% and 16.2%] ( P<0.05). Antibiotics duration in the hLOS group was longer than the other two groups [19 (14, 27) d vs. 15 (12, 20) d and 14 (12, 19) d] ( P<0.05). Conclusions:The clinical characteristics of neonatal sepsis vary among different types of infections, and it is necessary to establish appropriate prevention, control, diagnosis and treatment protocols.

Comparison of mortality and survival without major morbidities of very preterm infants with very low birth weight from Japan and Brazil / Comparação entre mortalidade e sobrevida sem morbidades importantes dos recém-nascidos prematuros de muito baixo peso entre o Japão e o Brasil

Abstract Objective: This study was carried out to understand the disparities in mortality and survival without major morbidities among very premature and very low birth weight infants between participating Neonatal Intensive Care Units (NICUs) from the Brazilian Network on Neonatal Research (RBPN) and the Neonatal Research Network of Japan (NRNJ). Methods: Secondary data analysis of surveys by the RBPN and NRNJ was performed. The surveys were conducted in 2014 and 2015 and included 187 NICUs. Primary outcome was mortality or survival without any major morbidity. Logistic regression analysis adjustment for confounding factors was used. Results: The study population consisted of 6,406 infants from the NRNJ and 2,319 from the RBPN. Controlling for various confounders, infants from RBPN had 9.06 times higher adjusted odds of mortality (95%CI 7.30-11.29), and lower odds of survival without major morbidities (AOR 0.36; 95%CI 0.32-0.41) compared with those from the NRNJ. Factors associated with higher odds of mortality among Brazilian NICUs included: Air Leak Syndrome (AOR 4.73; 95%CI 1.26-15.27), Necrotizing Enterocolitis (AOR 3.25; 95%CI 1.38-7.26), and Late Onset Sepsis (LOS) (AOR 4.86; 95%CI 2.25-10.97). Conclusions: Very premature and very low birth weight infants from Brazil had significantly higher odds for mortality and lower odds for survival without major morbidities in comparison to those from Japan. Additionally, we identified the factors that increased the odds of in-hospital neonatal death in Brazil, most of which was related to LOS.

RESUMO Objetivo: Este estudo foi realizado para compreender as disparidades na mortalidade e sobrevivência sem as principais morbidades entre recém-nascidos muito prematuros e de muito baixo peso entre Unidades de Terapia Intensiva Neonatal (UTINs) participantes da Rede Brasileira de Pesquisas Neonatais (RBPN) e Rede de Pesquisa Neonatal do Japão (NRNJ). Métodos: Foi realizada uma análise dos dados secundários dos bancos de dados da RBPN e da NRNJ. As pesquisas foram realizadas em 2014 e 2015 e incluíram 187 UTINs. O desfecho primário foi mortalidade ou sobrevida sem qualquer morbidade importante. Utilizou-se a análise de regressão logística com ajuste para os fatores de confusão. Resultados: A população do estudo foi composta por 6.406 recém-nascidos do NRNJ e 2.319 do RBPN. Ajustando para diversos fatores de confusão, os prematuros da RBPN tiveram 9,06 vezes maiores chances de mortalidade (IC95% 7,30-11,29) e menores chances de sobrevivência sem morbidades importantes (AOR 0,36; IC95% 0,32-0,41) em comparação com os da NRNJ. Fatores associados a maiores chances de mortalidade entre as UTINs brasileiras incluíram: síndrome de escape de ar (AOR 4,73; IC95% 1,26-15,27), enterocolite necrosante (AOR 3,25; IC95% 1,38-7,26) e sepse de início tardio (AOR 4,86; IC95% 2,25-10,97). Conclusões: Os recém-nascidos muito prematuros e de muito baixo peso do Brasil apresentaram chances significativamente maiores de mortalidade e menores chances de sobrevivência sem as principais morbidades em comparação aos do Japão. Além disso, identificamos os fatores que aumentam as chances da morte neonatal no Brasil, sendo a maioria relacionada à sepse tardia.

Caracterización de la infección asociada a la asistencia sanitaria en la Neonatología del hospital materno provincial

Introducción: Las infecciones asociadas a la asistencia sanitaria constituyen un problema de salud actual en los servicios de Neonatología. En los últimos tiempos su complejidad ha aumentado debido a que la atención brindada a neonatos inmaduros, susceptibles a la colonización microbacteriana, se encuentra mediada por el uso de procedimientos invasivos que facilitan la entrada de las infecciones. Objetivo: Caracterizar la infección asociada a la asistencia sanitaria en la Neonatología del hospital materno provincial. Métodos: Se realizó un estudio observacional descriptivo retrospectivo de corte transversal con el objetivo de caracterizar la infección asociada a la asistencia sanitaria en la Neonatología del Hospital Materno Provincial Ana Betancourt de Mora en la provincia Camagüey, período comprendido del 1ro de enero al 31 de diciembre del año 2022. El universo de estudio estuvo constituido por todos los neonatos ingresados en el servicio de Neonatología y la muestra a discreción la conformaron los 143 pacientes con sepsis nosocomial. Resultados: Los neonatos con infección asociada a la asistencia sanitaria más afectados fueron los de edad gestacional entre las 31-36 semanas, peso 1 500-2 499 gramos, parto vía cesárea. Como factores maternos la infección de vías urinarias/vaginosis y los neonatales la prematuridad seguido por el catéter epicutáneo; en cuanto a la localización la infección respiratoria con mayor número de casos y los gérmenes Gram negativos el Enterobacter gergoviae con la mayor incidencia. Conclusiones: Tanto la modificación como el conocimiento de los factores de riesgo serán impactos favorables para su disminución.

Introduction: Infections associated with health care (IAAS) are a current health problem in Neonatology services. In recent times, its complexity has increased because the care provided to immature neonates, susceptible to mycobacterial colonization, is mediated by the use of invasive procedures that facilitate the entry of germs. Objective: To characterize healthcare associated infections in the Neonatology of the provincial maternity hospital. Methods: A cross-sectional retrospective descriptive observational study was carried out with the aim of characterizing the infection associated with health care in the Neonatology of the Ana Betancourt de Mora Provincial Maternity Hospital in the province of Camagüey, from January 1st to December 31st, 2022. The study universe consisted of all neonates admitted to the Neonatology service and the sample at discretion was made up of 143 patients with nosocomial sepsis. Results: The most affected neonates with healthcare-associated infection were those of gestational age between 31-36 weeks, weight 1500-2499 grams, delivery via cesarean section. As maternal factors urinary tract infection / vaginosis and neonatal prematurity followed by the epicutaneous catheter; regarding the location, the respiratory infection with the highest number of cases and the Gram negative germs the Enterobacter gergoviae with the highest incidence. Conclusions: Both the modification and the knowledge of the risk factors will be favorable impacts for their reduction.

The financial impact of neonatal sepsis on the Brazilian Unified Health System

Abstract Objective To evaluate the hospital cost of newborn infants diagnosed with sepsis from the perspective of the Brazilian Public Health System over 11 years. Method Cross-sectional study that analyzed secondary data from the databases of the Hospital Information System of the Brazilian Public Health System. Infants hospitalized between 0‒29 days after birth with a diagnosis of sepsis from 2008 to 2018 were included. The diagnosis used in the study was the one that the hospital considered the main diagnosis at admission. Costs were analyzed in US dollars and reflected the amount paid by the Brazilian Public Health System to the hospitals for the informed diagnosis upon admission. The costs were evaluated as the total per admission, and they were compared among Brazilian geographic regions, among etiologic agents, and between neonates with the diagnosis of sepsis that survived or died. Results From 2008 to 2018, 47,554 newborns were hospitalized with sepsis (148.04 cases per 100,000 live births), with an average cost of US$ 3345.59 per hospitalization, ranging from US$ 2970.60 in the North region to US$ 4305.03 in the Midwest. Among sepsis with identified agents, the highest mean cost was related to Gram-negative agents, and the lowest to Streptococcus agalactiae sepsis. Patients with sepsis who died had a higher cost than the survivors (t-test; p= 0.046). Conclusions The evaluation of costs related to neonatal sepsis in the country during an 11-year period shows the economic impact of morbidity that may be avoided by improving the quality of neonatal care.