Herpes virus entry mediator signaling blockade produces mortality in neonatal sepsis through induced cardiac dysfunction.

Introduction: Sepsis remains a major source of morbidity and mortality in neonates, and characterization of immune regulation in the neonatal septic response remains limited. HVEM is a checkpoint regulator which can both stimulate or inhibit immune responses and demonstrates altered expression after sepsis. We hypothesized that signaling via HVEM would be essential for the neonatal response to sepsis, and that therefore blockade of this pathway would improve survival to septic challenge. Methods: To explore this, neonatal mice were treated with cecal slurry (CS), CS with Anti-HVEM antibody (CS-Ab) or CS with isotype (CS-IT) and followed for 7-day survival. Mice from all treatment groups had thymus, lung, kidney and peritoneal fluid harvested, weighed, and stained for histologic evaluation, and changes in cardiac function were assessed with echocardiography. Results: Mortality was significantly higher for CS-Ab mice (72.2%) than for CS-IT mice (22.2%). CS resulted in dysregulated alveolar remodeling, but CS-Ab lungs demonstrated significantly less dysfunctional alveolar remodeling than CS alone (MCL 121.0 CS vs. 87.6 CS-Ab), as well as increased renal tubular vacuolization. No morphologic differences in alveolar septation or thymic karyorrhexis were found between CS-Ab and CS-IT. CS-Ab pups exhibited a marked decrease in heart rate (390.3 Sh vs. 342.1 CS-Ab), stroke volume (13.08 CS-IT vs. 8.83 CS-Ab) and ultimately cardiac output (4.90 Sh vs. 3.02 CS-Ab) as well as a significant increase in ejection fraction (73.74 Sh vs. 83.75 CS-Ab) and cardiac strain (40.74 Sh vs. 51.16 CS-Ab) as compared to CS-IT or Sham animals. Discussion: While receptor ligation of aspects of HVEM signaling, via antibody blockade, appears to mitigate aspects of lung injury and thymic involution, stimulatory signaling via HVEM still seems to be necessary for vascular and hemodynamic resilience and overall neonatal mouse survival in response to this experimental polymicrobial septic insult. This dissonance in the activity of anti-HVEM neutralizing antibody in neonatal animals speaks to the differences in how septic cardiac dysfunction should be considered and approached in the neonatal population.

Time to Death and Its Predictors among Neonates Hospitalized with Sepsis in Eastern Ethiopia.

Background: Although neonatal sepsis is a major public health problem contributing to 30-50% of neonatal deaths in low- and middle-income countries, data on predictors of time to death are limited in Eastern Ethiopia. This study is aimed at determining predictors of time to death among neonates with sepsis admitted in public hospitals in Eastern Ethiopia. Methods: An institutional-based retrospective cohort study was conducted among 415 neonates admitted to referral hospitals in Eastern Ethiopia with sepsis from January 1, 2021, to December 31, 2021. Data were collected from medical records by using structured checklist and entered using EpiData 3.1 and analyzed using Stata 17. The Kaplan-Meier curves and log-rank tests were used to describe survival experience among different categories. The proportional hazard assumption and goodness of fit for the Cox regression model were checked. The Cox regression model was used to identify the significant predictors. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. Finally, statistical significance was set at a p value < 0.05 in the Cox regression analysis. Results: Of the 415 neonates with neonatal sepsis, 71 (17.1%) (95% CI: 13.60-21.08) died at discharge, with a median time to death of 14 days. The overall incidence rate of mortality was 36.5 per 1000 neonate days. Low birthweight (AHR = 2.50; 95% CI: 1.15-5.44), maternal age ≥ 35 years (AHR = 3.17; 95% CI: 1.11, 9.04), low fifth-minute Apgar score (AHR: 2.32; 95% CI: 1.30-4.14), and late initiation of breastfeeding (AHR = 4.82; 95% CI: 1.40-16.65) were independent predictors of mortality among neonates with sepsis. Conclusions: Almost one in five neonates with sepsis died at discharge. Low birthweight, maternal age ≥ 35 years, low fifth-minute Apgar score, and late initiation of breastfeeding were predictors of mortality.

A decade of neonatal sepsis in Stockholm, Sweden: Gram-positive pathogens were four times as common as Gram-negatives.

PURPOSE: To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016. METHODS: A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency. RESULTS: We identified 357 infants with GPB-BSI, representing an incidence of 1.47/1000 live births (LB). Group B streptococcus (GBS) was the most common pathogen causing BSI in full-term infants and early-onset sepsis (EOS) (0.20/1000 LB), while coagulase-negative staphylococci (CoNS) were predominant in infants born very preterm and in late-onset sepsis (LOS) (0.79/1000 LB). There were no fatal GBS BSI cases, but 10.2% developed meningitis. The GPB case fatality rate was 9.5% and the sepsis fatality rate 2.8%. In GPB-BSI, 1/10 did not have an elevated C-reactive protein level. Staphylococcus aureus (S. aureus) BSI increased during the study period, but no methicillin or vancomycin resistant strains were found. The antimicrobial resistance (AMR) rate was highest in CoNS isolates. CONCLUSION: GPB-BSI was four times more common than Gram-negative BSI in neonates but resulted in lower mortality rate. GBS was the most common pathogen in full-term infants and in EOS. CoNS was the most common pathogen in LOS and infants born very preterm, and the AMR rate was high in these isolates. The increasing trend of S. aureus BSI indicates a need of further investigation.

Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis.

OBJECTIVES: A systematic review with met-analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths. SEARCH STRATEGY: PubMed, Scopus and Web of Science databases were searched in March 2023. SELECTION CRITERIA: Randomised controlled trials comparing intrapartum single-dose of azithromycin with placebo. DATA COLLECTION AND ANALYSIS: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random-effects Mantel-Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach. MAIN RESULTS: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55-0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22-1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30-0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56-0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65-2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76-1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96-1.09; moderate certainty evidence). CONCLUSIONS: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates.

Effect of Intrapartum Azithromycin vs Placebo on Neonatal Sepsis and Death: A Randomized Clinical Trial.

Importance: Neonatal sepsis is a leading cause of neonatal mortality. New interventions are needed to decrease neonatal sepsis and mortality in regions with highest burden. Objective: To evaluate the efficacy of intrapartum azithromycin to reduce neonatal sepsis or mortality, as well as neonatal and maternal infections. Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial enrolled and followed up birthing parents and their infants at 10 health facilities in The Gambia and Burkina Faso, West Africa, between October 2017 and May 2021. Interventions: Participants were assigned at random to receive oral azithromycin (2 g) or placebo (ratio 1:1) during labor. Main Outcomes and Measures: The primary outcome was a composite of neonatal sepsis or mortality, with the former defined based on microbiologic or clinical criteria. Secondary outcomes were neonatal infections (skin, umbilical, eye and ear infections), malaria, and fever; postpartum infections (puerperal sepsis, mastitis), fever, and malaria; and use of antibiotics during 4-week follow-up. Results: The trial randomized 11 983 persons in labor (median age, 29.9 years). Overall, 225 newborns (1.9% of 11 783 live births) met the primary end point. The incidence of neonatal mortality or sepsis was similar in the azithromycin and placebo groups (2.0% [115/5889] vs 1.9% [110/5894]; risk difference [RD], 0.09 [95% CI, -0.39 to 0.57]), as was the incidence of neonatal mortality (0.8% vs 0.8%; RD, 0.04 [95% CI, -0.27 to 0.35]) and neonatal sepsis (1.3% vs 1.3%; RD, 0.02 [95% CI, -0.38 to 0.43]). Newborns in the azithromycin group compared with the placebo group had lower incidence of skin infections (0.8% vs 1.7%; RD, -0.90 [95% CI, -1.30 to -0.49]) and need for antibiotics (6.2% vs 7.8%; RD, -1.58 [95% CI, -2.49 to -0.67]). Postpartum parents in the azithromycin group had lower incidence of mastitis (0.3% vs 0.5%; RD, -0.24 [95% CI, -0.47 to -0.01]) and puerperal fever (0.1% vs 0.3%; RD, -0.19 [95% CI, -0.36 to -0.01]). Conclusions and Relevance: Azithromycin administered orally during labor did not reduce neonatal sepsis or mortality. These results do not support routine introduction of oral intrapartum azithromycin for this purpose. Trial Registration: ClinicalTrials.gov Identifier: NCT03199547.

Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.

BACKGROUND: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. METHODS: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. RESULTS: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. CONCLUSIONS: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).

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.

Mortalidad por sepsis neonatal entre los años 2016 y 2020 en Chile: una mirada nacional / Mortality due to neonatal sepsis between 2016 and 2020 in Chile: a national perspective

Introducción: La sepsis neonatal (SN) es una infección sistémica que ocurre antes de los 90 días de vida y que representa una amenaza potencialmente mortal. Esta investigación busca describir la tendencia de defunción por SN en Chile, durante el periodo 2016-2020. Materiales y métodos: Estudio descriptivo observacional, que incluyó a niños fallecidos por SN (n=249) en el periodo 2016-2020 en Chile según datos del departamento de estadísticas e información de salud de Chile. Las variables estudiadas fueron: año de fallecimiento, grupo etario, sexo, región y agente etiológico. No se requirió comité de ética. Resultados: El 2020 tuvo la menor tasa de mortalidad por SN (0,17) y el 2017 la mayor (0,31). El grupo etario de 0-2 días de nacido tuvo la mayor tasa de mortalidad (0,07), mientras que el grupo de 27-28 días corresponde a la menor (0,00). La región de Antofagasta tuvo la mayor mortalidad (0,44) y la región de Magallanes la menor (0,11). La tasa de mortalidad promedio en hombres corresponde a 0,12 y en mujeres a 0,10. En el 89,16% de los casos no se identificó el agente etiológico. Discusión: La mayor mortalidad en 2017 podría deberse a una proporción más alta de nacimientos pretérmino en dicho año. La mayor cantidad de defunciones a menor edad cronológica estaría relacionada con su inmadurez inmunológica. La no detección del agente etiológico pudo deberse al bajo rendimiento de los hemocultivos. Sin embargo, faltan más investigaciones acerca de la incidencia y mortalidad por sepsis neonatal.

Introduction: Neonatal sepsis (NS) is a systemic infection that occurs before 90 days of life and represents a life-threatening threat. This research seeks to describe the trend of death by NS in Chile, during the period 2016-2020. Materials and methods: Observational descriptive study, which included children who died due to NS (n=249) in the period 2016-2020 in Chile, according to data from the Department of Statistics and Health Information of Chile. The variables studied were: year of death, age group, sex, region and etiological agent. No ethics committee was required. Results: 2020 had the lowest mortality rate due to NS (0.17) and 2017 the highest (0.31). The age group of 0-2 days of birth had the highest mortality rate (0.07), while the group of 27-28 days corresponds to the lowest (0.00). The Antofagasta region had the highest mortality (0.44) and the Magallanes region the lowest (0.11). The average mortality rate in men corresponds to 0.12 and in women to 0.10. In 89.16% of the cases, the etiological agent was not identified. Discussion: The higher mortality in 2017 could be due to a higher proportion of preterm births in that year. The greater number of deaths at a lower chronological age would be related to their immunological immaturity. The non-detection of the etiological agent could be due to the low yield of the blood cultures. However, more research on the incidence and mortality from neonatal sepsis is lacking.

The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review.

Sepsis causes high rates of morbidity and mortality in NICUs. The estimated incidence varies between 5 and 170 per 1000 births, depending on the social context. In very low birth-weight neonates, the level of mortality increases with the duration of hospitalization, reaching 36% among infants aged 8-14 days and 52% among infants aged 15-28 days. Early diagnosis is the only tool to improve the poor prognosis of neonatal sepsis. Blood culture, the gold standard for diagnosis, is time-consuming and poorly sensitive. C-reactive protein and procalcitonin, currently used as sepsis biomarkers, are influenced by several maternal and fetal pro-inflammatory conditions in the perinatal age. Presepsin is the N-terminal fragment of soluble CD14 subtype (sCD14-ST): it is released in the bloodstream by monocytes and macrophages, in response to bacterial invasion. Presepsin seems to be a new, promising biomarker for the early diagnosis of sepsis in neonates as it is not modified by perinatal confounding inflammatory factors. The aim of the present review is to collect current knowledge about the role of presepsin in critically ill neonates.

Diagnostic, Prognostic, Predictive, and Monitoring Role of Neutrophil CD11b and Monocyte CD14 in Neonatal Sepsis.

BACKGROUND: Sepsis is a critical medical condition that requires additional diagnostic considerations. Recently, focus has shifted to the diagnosis of sepsis using new markers to overcome the limitations of traditional laboratory diagnostic modalities. Neutrophil CD11b (nCD11b) and monocyteCD14 (mCD14) cell surface antigens have been shown to be useful in such diagnostic consideration. AIM: To investigate the diagnostic, monitoring, prognostic, and predictive roles of nCD11b and mCD14 as sepsis biomarkers in comparison to each other and to traditional laboratory sepsis parameters in order to select the best fit for routine daily use in neonatal intensive care units (NICUs). SUBJECT: The study included 188 neonates from Ain Shams University Hospitals' NICUs, who were divided into two groups: the control group (n = 100) and the sepsis group (n = 88). Highly sensitive CRP (hs-CRP), complete blood count (CBC), blood culture, and nCD11b and mCD14 evaluations were all part of the laboratory sepsis evaluation (done by flow cytometry technology). Positive blood culture results (BACT/ALERT system) confirmed the sepsis diagnosis. Twenty-four enrolled sepsis neonates were subjected to follow-up assessments, and they were divided into two groups based on clinical improvement: improved sepsis and sepsis without improvement. In order to predict performance evaluation, the subjected neonates were reclassified according to their outcome into survivors' and nonsurvivors' group. RESULTS: Sepsis patients had a significant increase in mCD14 MFI values when compared to controls. With sensitivity 75.4 percent, specificity 71.9 percent, efficacy 73.3 percent, and AUC 0.703, mCD14 MFI at cutoff 9.36 could distinguish the presence of septicemia. Significant increases in both mCD14 MFI and nCD11b MFI (P = 0.001) were observed in the severe sepsis/septic shock group compared to the nonsevere sepsis group. The combined measurement of CD14 MFI at cutoff 9.97 and CD14 percent at cutoff 44.7 percent yielded the best predictive performance. CONCLUSION: Sepsis patients had a significant increase in mCD14 MFI comparable to the controls. mCD14 MFI demonstrated better diagnostic, prognostic, and predictive results than nCD11b. hs-CRP outperformed mCD14 and nCD11b in terms of diagnostic efficacy and AUC. In the monitoring of sepsis patients, both mCD14 and nCD11b produced unsatisfactory results. Currently, the routine use of mCD14 or nCD11b as sepsis biomarkers in neonatal ICUs is not justified.

Early-Onset Sepsis Among Very Preterm Infants.

OBJECTIVES: To determine the epidemiology and microbiology of early-onset sepsis (EOS) among very preterm infants using a nationally representative cohort from academic and community hospitals to inform empirical antibiotic guidance, highlight risk factors for infection, and aid in prognostication for infected infants. METHODS: Prospective observational study of very preterm infants born weighing 401 to 1500 g or at 22 to 29 weeks' gestational age from January 2018 to December 2019 in 753 Vermont Oxford Network centers. EOS was defined as a culture-confirmed bacterial infection of the blood or cerebrospinal fluid in the 3 days after birth. Demographics, clinical characteristics, and outcomes were compared between infants with and without EOS. RESULTS: Of 84 333 included infants, 1139 had EOS for an incidence rate of 13.5 per 1000 very preterm births (99% confidence interval [CI] 12.5-14.6). Escherichia coli (538 of 1158; 46.5%) and group B Streptococcus (218 of 1158; 18.8%) were the most common pathogens. Infected infants had longer lengths of stay (median 92 vs 66 days) and lower rates of survival (67.5% vs 90.4%; adjusted risk ratio 0.82 [95% CI 0.79-0.85]) and of survival without morbidity (26.1% vs 59.4%; adjusted risk ratio 0.66 [95% CI 0.60-0.72]). CONCLUSIONS: In a nationally representative sample of very preterm infants with EOS from 2018 to 2019, approximately one-third of isolates were neither group B Streptococcus nor E coli. Three-quarters of all infected infants either died or survived with a major medical morbidity. The profoundly negative impact of EOS on very preterm infants highlights the need for novel preventive strategies.

Antibiotic Use in Neonatal Intensive Care Units in China: A Multicenter Cohort Study.

OBJECTIVE: To provide national-level antibiotic use data from Chinese neonatal intensive care units to inform future antimicrobial stewardship using a large contemporary cohort of preterm infants in China. STUDY DESIGN: This retrospective cohort study enrolled all infants less than 340/7 weeks of gestation admitted to 25 tertiary neonatal intensive care units across China between May 1, 2015, and April 30, 2018. The antibiotic use rate (AUR) was defined as the number of days an infant was prescribed with 1 or more antibiotics divided by the total length of hospital stay. RESULTS: Among 24 597 eligible infants, 21 736 (88.4%) infants received antibiotics. The median AUR was 441 per 1000 patient-days (IQR, 242-692 per 1000 patient-days). The median duration of each antibiotic course was 9 days (IQR, 6-14 days). Overall, 64.6% infants received broad-spectrum antibiotics, with a median broad-spectrum AUR of 250 per 1000 patient-days (IQR, 0-500 per 1000 patient-days), accounting for 70.7% of all antibiotic use days. Overall, 68.7% of all antibiotic use occurred among infants without infection-related morbidities, with a median duration of 8 days (IQR, 6-13 days) for each course. Only 22.9% episodes of culture-negative sepsis were prescribed with antibiotics for 7 or fewer days, and 34.7% were treated with antibiotics for more than 14 days. For early antibiotic use, the median duration of antibiotic therapy within 7 days after birth was 7 days (IQR, 4-7 days). CONCLUSIONS: A high AUR among infants without infections, prolonged antibiotic durations, and excessive use of broad-spectrum antibiotics were the main problems of antibiotic use in Chinese neonatal intensive care units and should be high-impact focuses for future stewardship interventions.

Fatal Neonatal Sepsis Associated with Human Adenovirus Type 56 Infection: Genomic Analysis of Three Recent Cases Detected in the United States.

BACKGROUND: Human adenovirus (HAdV)-D56 was first described in 2011 by genomics analysis of a strain isolated in France in 2008 from a fatal case of neonatal infection. Since then, it has been reported in cases of keratoconjunctivitis and male urethritis. Three epidemiologically unrelated fatal cases of neonatal sepsis associated with infection by HAdV-D strains with a similar genetic makeup were documented in the United States between 2014 and 2020. METHODS: Whole genome sequences were obtained for the isolated strains, and genomics analyses were conducted to compare them to phylogenetically related HAdV-D genomic sequences available in GenBank. RESULTS: The three new US strains were indistinguishable by in silico restriction enzyme analysis. Their genome sequences were 99.9% identical to one another and to the prototype strain isolated in 2008 from a similar context of disease. The phylogenetic reconstruction revealed a highly supported clustering of all HAdV-D56 strains isolated in various countries since 1982. Our comparison to serologically intermediate strains 15/H9 described in the literature indicated that HAdV-D56-like viruses have circulated worldwide since the late 1950s. CONCLUSION: As with other HAdV-D genotypes with the ability to infect ocular and genital mucosae, the risk of severe prenatal or perinatal HAdV-D56 infection must be considered.

Risk Factors Associated With 30-Day Mortality Among Neonates With A. baumannii Sepsis.

BACKGROUND: Acinetobacter baumannii sepsis constitutes an extreme threat with a poor prognosis and is a difficult infection to control, especially in Asia. Moreover, a knowledge gap in the risk of mortality in neonatal A. baumannii sepsis still exists. METHODS: This study aimed to identify the risk factors of mortality in neonates with A. baumannii sepsis in Thailand from 1996 to 2019. A multivariable logistic regression model was analyzed for nonsurvivors and survivors of neonatal A. baumannii sepsis. RESULTS: In a 24-year period, 91 neonates with A. baumannii sepsis were reviewed. The median (interquartile range) gestational age and birth weight were 33 (28.5, 37.5) weeks and 1740 (987.5, 2730.0) g, respectively. The 30-day case fatality rate was 36.3% (33/91). In univariable analysis, nonsurvivors of neonatal A. baumannii sepsis was associated with smaller neonates, lower Apgar scores, septic shock, mechanical ventilation, umbilical catheterization, neutropenia, severe thrombocytopenia, carbapenem-resistant A. baumannii sepsis, inadequate empiric antimicrobial therapy, and acute kidney injury. In multivariable analysis, nonsurvivors of neonatal A. baumannii sepsis were associated with septic shock (adjusted odds ratio [OR] = 41.38; 95% confidence intervals [CI]: 3.42-501.13; P = 0.003), severe thrombocytopenia (adjusted OR = 33.70; 95% CI: 3.44-330.55; P = 0.002), and inadequate empiric antimicrobial therapy (adjusted OR = 10.05; 95% CI: 1.40-71.98; P = 0.02). CONCLUSION: In high multidrug-resistant areas, empiric treatment with broader spectrum antimicrobials should be considered in neonates with sepsis shock or severe thrombocytopenia.

Causes of preterm and low birth weight neonatal mortality in a rural community in Kenya: evidence from verbal and social autopsy.

BACKGROUND: Under-five mortality in Kenya has declined over the past two decades. However, the reduction in the neonatal mortality rate has remained stagnant. In a country with weak civil registration and vital statistics systems, there is an evident gap in documentation of mortality and its causes among low birth weight (LBW) and preterm neonates. We aimed to establish causes of neonatal LBW and preterm mortality in Migori County, among participants of the PTBI-K (Preterm Birth Initiative-Kenya) study. METHODS: Verbal and social autopsy (VASA) interviews were conducted with caregivers of deceased LBW and preterm neonates delivered within selected 17 health facilities in Migori County, Kenya. The probable cause of death was assigned using the WHO International Classification of Diseases (ICD-10). RESULTS: Between January 2017 to December 2018, 3175 babies were born preterm or LBW, and 164 (5.1%) died in the first 28 days of life. VASA was conducted among 88 (53.7%) of the neonatal deaths. Almost half (38, 43.2%) of the deaths occurred within the first 24 h of life. Birth asphyxia (45.5%), neonatal sepsis (26.1%), respiratory distress syndrome (12.5%) and hypothermia (11.0%) were the leading causes of death. In the early neonatal period, majority (54.3%) of the neonates succumbed to asphyxia while in the late neonatal period majority (66.7%) succumbed to sepsis. Delay in seeking medical care was reported for 4 (5.8%) of the neonatal deaths. CONCLUSION: Deaths among LBW and preterm neonates occur early in life due to preventable causes. This calls for enhanced implementation of existing facility-based intrapartum and immediate postpartum care interventions, targeting asphyxia, sepsis, respiratory distress syndrome and hypothermia.

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis.

Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case-control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for sepsis. Furthermore, patients with high circulatory MYD88 levels were associated with poor survival, as revealed by Kaplan-Meier curves analysis. MYD88, NFKB1, and IL6 transcripts showed association with different poor-outcome manifestations. Clustering analysis split the patient cohort into three distinct groups according to their transcriptomic signature and CRP levels. In conclusion, the study TLR pathway-related transcripts have a gender-specific signature, diagnostic, and prognostic clinical utility in neonatal sepsis.

Bloodstream Infections in Preterm Neonates and Mortality-Associated Risk Factors.

OBJECTIVE: To investigate the association of early (±4 hours after onset of bloodstream infection) clinical and laboratory variables with episode-related mortality (<7 days). STUDY DESIGN: This 2-site retrospective study included 142 neonates born at <35 weeks of gestational age with positive blood/cerebrospinal fluid (CSF) culture at >72 hours of age from organisms other than coagulase-negative Staphylococcus. Early variables were compared between those with bloodstream infection-related mortality and survivors. Multivariable analysis was conducted for the primary outcome, and the area under the curve (AUC) was estimated for relevant variables. RESULTS: The neonates who died were of lower gestational age at disease onset. After adjusting for relevant variables, lowest mean blood pressure (MBP) (aOR, 0.10; 95% CI, 1.02-1.19) and highest base deficit (aOR, 1.18; 95% CI, 1.06-1.32) were independently associated with mortality. The AUC was 0.87 (95% CI, 0.78-0.96) for base deficit, increasing to 0.91 (95% CI, 0.83-0.99) with the addition of MBP. CONCLUSION: Low MBP and high base deficit within ±4 hours of bloodstream infection onset identify preterm neonates at risk of mortality.