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Background: Neonatal sepsis is a serious systemic infection that might be fatal. Early diagnosis is challenging. The c-reactive protein (CRP)/albumin ratio is a promising biomarker that may help with early diagnosis and timely management of sepsis. Aim of the work: to study the sensitivity and specificity of the CRP/albumin ratio as a diagnostic marker of neonatal sepsis in preterm newborns. Patients and Methods: in this case-control study CRP/albumin ratio was estimated in 154 preterm newborns admitted to Neonatal Intensive Care Units (NICUs) of Cairo University Children's Hospitals. They were divided into 2 groups. Group (I), the sepsis group “based on positive blood culture” (n=54), and group (II), a control group, with no clinical signs or laboratory evidence of sepsis (n=100). Results: The mean age of newborns in the sepsis group was 3 ± 2.5 days vs 4.5 ± 2.5 days for the control group. The sepsis group had a mean ± SD CRP/albumin ratio higher than that of the control group (18.5 ± 20 vs 0.6± 0.7, p= 0.00). 30 (55%) of those in the sepsis group died; they had a mean ± SD CRP/albumin ratio of 20± 21, vs 15 ± 17 for those who survived (p value=0.3). Neonatal Sepsis was best diagnosed by the CRP/albumin ratio above the cutoff value of 1.5 with 100 % sensitivity, 95% specificity, 91.5 % positive predictive value (PPV), 100 % negative predictive value (NPV), (area under the curve (AUC)= 0.99, and 95 % confidence interval (CI) 0.983 - 1), which was not different than that of CRP alone (p=0.800). CRP above the cutoff point of 4.3 showed 96.3 % sensitivity, 96% specificity, 92.9 % PPV, 98 % NPV, (AUC= 0.99 , 95 % CI 0.983 - 1). The I/T ratio (shift to the left) above the cutoff point of 0.2 showed 64.8% sensitivity, 100 % specificity, 100% PPV and 84% NPV (AUC= 0.94 , 95% CI 0.891 - 0.973). Conclusion: CRP/albumin ratio is a highly sensitive and specific early diagnostic biomarker for neonatal sepsis in premature newborns that has marginal superiority to the CRP in the diagnosis of neonatal bacterial sepsis. More studies are needed to validate the sensitivity and specificity of a score that combines both the CRP/ albumin ratio above 1.2 and the I/T ratio above 0.2 in predication of true positive cases and exclusion of the true negative cases.

Abstract Background Early-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes. Purpose The objective of this study was to examine the present time of antibiotic administration in preterm infants with suspected EOS and the factors that contribute to delayed antibiotic initiation. Methods In this retrospective study in China, a total of 82 early preterm infants with suspected EOS between December 2021 and March 2023 were included. The study utilized a linear regression analytical approach to identify independent factors that contribute to delayed antibiotic administration. Results The mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (β = 0.07, P = 0.013), penicillin skin test (PST) timing (β = 0.06, P

Background: Early and late-onset neonatal sepsis (EOS and LOS) are significant causes of morbidity and mortality in newborns. Accurate and timely diagnosis is critical for effective management. The Cluster of Differentiation 163 (CD163) level in the blood has emerged as a potential biomarker for sepsis, reflecting the immune response to infection. Objective: This study aimed to evaluate the role of CD163 levels in predicting neonatal sepsis and its correlation with other clinical and laboratory parameters. Methods: A comparative study was conducted involving 90 neonates divided into three groups: EOS, LOS, and a control group. Clinical data, presenting complaints, maternal risk factors, and laboratory findings were analyzed. CD163 levels were measured and correlated with clinical outcomes. Results: CD163 concentrations were markedly higher in both EOS and LOS cohorts relative to the control group. In the LOS cohort, CD163 levels demonstrated a positive association with platelet count and an inverse relationship with hemoglobin concentrations. No significant gender differences in CD163 levels were observed. Conclusion: CD163 serves as a critical biomarker for the prompt identification of neonatal sepsis, with a threshold value set at ≥ 4.5%. Its use in clinical practice could enhance early diagnosis and treatment as well as reduction of neonatal morbidity and mortality. [ABSTRACT FROM AUTHOR]

An accurate diagnosis of early-onset sepsis (EOS) is challenging because of subtle symptoms and the lack of a good diagnostic tool, resulting in considerable antibiotic overtreatment. A biomarker, discriminating between infected and non-infected newborns at an early stage of the disease, could improve EOS prediction. Numerous biomarkers have been tested, but have never been compared directly. We aimed to provide a comprehensive overview of early biomarkers and their diagnostic value in maternal samples, umbilical cord blood, and neonatal serum. PubMed-Medline, EMBASE, The Cochrane Library, and Web of Science were searched up to 1 March 2023, without restrictions on publication date, population, or language. Articles describing the diagnostic value of at least one biomarker in the detection of EOS in neonates, independent of gestational age, were included. The QUADAS-2 tool was used to assess study quality. Three independent researchers assessed the articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed with all manuscripts describing diagnostic accuracy using a random-effects model. Of 2296 identified articles, 171 reports were included in the systematic review and 69 in the meta-analysis. Literature showed mixed and inconsistent evidence for most biomarkers and sample types, because of a lack of a uniform EOS case definition, small sample sizes, and large heterogeneity between studies. Interesting markers were procalcitonin (pooled sensitivity 79%, 95% CI 71–84%; specificity 91%, 95% CI 83–96%, n = 11) and interleukin (IL)-6 (pooled sensitivity 83%, 95% CI 71–90%; specificity 87%, 95% CI 78–93%, n = 8) in umbilical cord blood and presepsin (pooled sensitivity 82%, 95% CI 62–93%; specificity 86%, 95% CI 73–93%, n = 3) and serum amyloid A (pooled sensitivity 92%, 95% CI 75–98%; specificity 96%, 95% CI 78–99%, n = 4) in neonatal serum. Studies on the combination of biomarkers were scarce. A biomarker stand-alone test is currently not reliable for direct antibiotic stewardship in newborns, although several biomarkers show promising initial results. Further research into biomarker combinations could lead to an improved EOS diagnosis, reduce antibiotic overtreatment, and prevent associated health-related problems. [ABSTRACT FROM AUTHOR]

Background: Early-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes. Purpose: The objective of this study was to examine the present time of antibiotic administration in preterm infants with suspected EOS and the factors that contribute to delayed antibiotic initiation. Methods: In this retrospective study in China, a total of 82 early preterm infants with suspected EOS between December 2021 and March 2023 were included. The study utilized a linear regression analytical approach to identify independent factors that contribute to delayed antibiotic administration. Results: The mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (β = 0.07, P = 0.013), penicillin skin test (PST) timing (β = 0.06, P < 0.001) and medical order timing (β = 0.04, P = 0.017) were significantly associated with the initial timing of antibiotic administration. Conclusions: There is an evident delay in antibiotic administration in preterm infants with suspected EOS in our unit. Severe RDS, PST postponement and delayed medical orders were found to be associated with the delayed use of antibiotics, which will be helpful for quality improvement efforts in the neonatal intensive care unit (NICU). [ABSTRACT FROM AUTHOR]

Introduction: Neonatal sepsis is associated with significant mortality and morbidity. Low-middle-income countries are disproportionately affected, but late-onset sepsis (LOS) still occurs in up to 20% of infants <28 weeks in high-income countries. Understanding site-specific data is vital to guide management. Methods: A retrospective cohort study was conducted at King Edward Memorial Hospital (KEMH), Perth. Infants admitted between January 2012 and June 2022 were included. Data were extracted from routine electronic databases. Incidence and aetiology of sepsis were determined and the association of sepsis with neonatal outcomes analysed. Results: During the study period, 23,395 newborns were admitted with a median gestation of 37 weeks and birth weight of 2,800 g. There were 370 sepsis episodes in 350 infants; 102 were early-onset sepsis (EOS) (1.6 per 1,000 live births), predominantly Streptococcus agalactiae (35, 34.3%) and Escherichia coli (27, 26.5%); 268 were LOS (0.9 per 1,000 inpatient days), predominantly coagulase-negative staphylococci (CONS) (156, 57.6%) and E. coli (30, 11.1%). The incidence of LOS declined from 2012 to 2022 (p = 0.002). Infants with EOS had increased brain injury (25.7% vs. 4.1%; p = 0.002) and mortality (18.8% vs. 1.6%; p < 0.001). Those with LOS had increased hospital stay (median 95 vs. 15 days; p < 0.001), mortality (15.3% vs. 1.6%; p = 0.018), necrotising enterocolitis (NEC) (7.4% vs. 0.5%; p < 0.001), and chronic lung disease (CLD) (58.1% vs. 5.9%; p = 0.005). Infants <28 weeks with sepsis were at increased risk of neurodevelopmental impairment compared to those without infection (43.2% vs. 30.9%, p = 0.027). Conclusions: While we observed a reduction in LOS incidence, sepsis remains associated with higher mortality, and in survivors with longer hospital stay and increased risk of brain injury, NEC, CLD, and neurodevelopmental impairment. [ABSTRACT FROM AUTHOR]

Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of culture-proven EOS in The Netherlands. In this retrospective study from 2019 to 2021, data were collected from 15 Dutch hospitals, comprising 13 regional hospitals equipped with Level I-II facilities and 2 academic hospitals equipped with Level IV facilities. Data included birth rates, number of neonates started on antibiotics for suspected EOS, number of neonates that continued treatment beyond 48 h and number of neonates with culture-proven EOS. Additionally, blood culture results were documented. Data were analysed both collectively and separately for regional and academic hospitals. A total of 103,492 live-born neonates were included. In 4755 neonates (4.6%, 95% CI 4.5–4.7), antibiotic therapy was started for suspected EOS, and in 2399 neonates (2.3%, 95% CI 2.2–2.4), antibiotic treatment was continued beyond 48 h. Incidence of culture-proven EOS was 1.1 cases per 1000 live births (0.11%, 95% CI 0.09–0.14). Overall, for each culture-proven EOS case, 40.6 neonates were started on antibiotics and in 21.7 neonates therapy was continued. Large variations in treatment rates were observed across all hospitals, with the number of neonates initiated and continued on antibiotics per culture-proven EOS case varying from 4 to 90 and from 4 to 56, respectively. The high number of antibiotic prescriptions compared to the EOS incidence and wide variety in clinical practice among hospitals in The Netherlands underscore both the need and potential for a novel approach to the management of neonates with suspected EOS. [ABSTRACT FROM AUTHOR]

Abstract Background Antibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit. Methods Retrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy. Results We included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P

Purpose: Our quality improvement study aimed to determine whether application of a neonatal early-onset sepsis calculator (NSC) among well-appearing infants born at ≥ 35 weeks’ gestation to mothers with chorioamnionitis decreases the number of lab evaluations (LEs) and antibiotic treatments (Abxs) without missing early-onset sepsis. Methods: We compared 2 years (January 1, 2019–January 3, 2021) of data from a historical-control group before implementation of the NSC to 1 year (January 4, 2021–December 31, 2021) of data from a calculator group after implementation of the NSC to evaluate whether LE and Abx decreased following implementation of the NSC on January 4, 2021. A P-value of < 0.05 was considered statistically significant for the chi-squared test, Fisher’s exact test, Student’s t-test, and Mann-Whitney U test used for the analyses. Results: In the historical-control group, 94% of infants received LE and Abx. Retrospective application of the NSC in the historical-control group decreased LE from 94% to 21% and Abx from 94% to 13%. In the calculator group, 14% and 5% of infants received LE and Abx, respectively, and none of the blood culture was positive. Median time from birth to antibiotic initiation was significantly longer (14.5 vs 3.8 hours; P = 0.0037) with no increase in median length of stay (2.3 vs 2.4 days; P = 0.02) after NSC implementation. No significant difference in neonatal intensive care unit admission was identified between groups (4% vs 1%; P = 0.15). Conclusions: There was a significant decrease in LE and Abx among well-appearing infants born at ≥ 35 weeks’ gestation to mothers with chorioamnionitis after implementation of the NSC without missing early-onset sepsis. There was no increase in neonatal intensive care unit admission or length of hospital stay in infants who received antibiotics later after they appeared equivocal or clinically ill in the calculator group. Larger prospective studies that include follow ups are needed to confirm that early-onset sepsis is not missed. (J Patient Cent Res Rev. 2024;11:29-35.)

Neonatal sepsis is a clinical syndrome mainly associated with a bacterial infection leading to severe clinical manifestations that could be associated with fatal sequalae. According to the time of onset, neonatal sepsis is categorized as early- (EOS) or late-onset sepsis (LOS). Despite blood culture being the gold standard for diagnosis, it has several limitations, and early diagnosis is not immediate. Consequently, most infants who start empirical antimicrobial therapy do not have an underlying infection. Despite stewardship programs partially reduced this negative trend, in neonatology, antibiotic overuse still persists, and it is associated with several relevant problems, the first of which is the increase in antimicrobial resistance (AMR). Starting with these considerations, we performed a narrative review to summarize the main findings and the future prospects regarding antibiotics use to treat neonatal sepsis. Because of the impact on morbidity and mortality that EOS and LOS entail, it is essential to start an effective and prompt treatment as soon as possible. The use of targeted antibiotics is peremptory as soon as the pathogen in the culture is detected. Although prompt therapy is essential, it should be better assessed whether, when and how to treat neonates with antibiotics, even those at higher risk. Considering that we are certainly in the worrying era defined as the "post-antibiotic era", it is still essential and urgent to define novel strategies for the development of antibacterial compounds with new targets or mechanisms of action. A future strategy could also be to perform well-designed studies to develop innovative algorithms for improving the etiological diagnosis of infection, allowing for more personalized use of the antibiotics to treat EOS and LOS. [ABSTRACT FROM AUTHOR]

Early-onset sepsis (EOS) is a global health issue, considered one of the primary causes of neonatal mortality. Diagnosis of EOS is challenging because its clinical signs are nonspecific, and blood culture, which is the current gold-standard diagnostic tool, has low sensitivity. Commonly used biomarkers for sepsis diagnosis, including C-reactive protein, procalcitonin, and interleukin-6, lack specificity for infection. Due to the disadvantages of blood culture and other common biomarkers, ongoing efforts are directed towards identifying innovative molecular approaches to diagnose neonates at risk of sepsis. This review aims to gather knowledge and recent research on these emerging molecular methods. PCR-based techniques and unrestricted techniques based on 16S rRNA sequencing and 16S–23S rRNA gene interspace region sequencing offer several advantages. Despite their potential, these approaches are not able to replace blood cultures due to several limitations; however, they may prove valuable as complementary tests in neonatal sepsis diagnosis. Several microRNAs have been evaluated and have been proposed as diagnostic biomarkers in EOS. T2 magnetic resonance and bioinformatic analysis have proposed potential biomarkers of neonatal sepsis, though further studies are essential to validate these findings. [ABSTRACT FROM AUTHOR]

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum and hematological biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM) and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided into two groups: group A, with PROM ≥ 18 h, and group B, with ROM < 18 h. Both groups were further split into subgroups: proven sepsis, presumed sepsis, and no sepsis. Descriptive statistics, analysis of variance (ANOVA) and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cell count from the first (p = 0.005) and third day (p = 0.028), and high C-reactive protein (CRP) values from the first day (p = 0.004). Procalcitonin (area under the curve—AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early-onset neonatal sepsis. (4) Conclusions: Our results outline the feasibility of using procalcitonin and CRP measured on the first day taken individually in order to increase the detection rate of early-onset neonatal sepsis, in the absence of positive blood culture. [ABSTRACT FROM AUTHOR]

(1) Background: Interleukin-6 (IL-6) levels act as an early infection marker preceding C-reactive protein (CRP) elevation. This study seeks to analyze IL-6 behavior in suspected early-onset sepsis (EOS) cases among term newborns, comparing it to that of CRP and evaluating IL-6's diagnostic utility. We also aim to assess the impact of maternal risk factors on EOS in term newborns, quantifying their influence for informed decision making. (2) Methods: The retrospective data analysis included 533 term newborns who were admitted to our hospital because of suspected EOS. IL-6, CRP, and the impact of maternal risk factors were analyzed in the context of EOS using binomial test, Chi-squared test, logistic and linear regression. (3) Results: In the cases of EOS, both IL-6 and CRP were elevated. The increase in CRP can be predicted by the initial increase in IL-6 levels. Among the assessed risk factors, intrapartum maternal fever (adjusted odds ratio 18.1; 95% CI (1.7–4.1)) was identified as the only risk factor significantly associated with EOS. (4) Conclusions: Employing IL-6 as an early infection marker enhanced EOS diagnostic precision due to its detectable early rise. However, caution is required, as elevations in IL-6 and CRP levels do not exclusively indicate EOS. Increased CRP levels in healthy newborns with maternal risk factors may be attributed to dynamics of vaginal labor. [ABSTRACT FROM AUTHOR]

Objective: The proportion of neonatal early‐onset sepsis (EOS) by gram‐negative bacteria has increased. The authors examined bacterial distribution in the amniotic membrane cultures of women with peripartum fever (PPF) and related perinatal outcomes. Methods: This retrospective study covered the period 2011 to 2019. The primary outcomes were Enterobacteriaceae‐positive birth culture rates in women with PPF and the trend of ampicillin resistance. Maternal and neonatal outcomes were compared between women with group B Streptococcus (GBS) and Enterobacteriaceae‐positive isolates. Bacterial distribution was also compared according to rupture of membrane (ROM) duration. Results: Among 621 women with PPF, the positive birth culture rate was 52%. Increasing prevalences of ampicillin‐resistant Enterobacteriaceae (81%) were noted. Positive birth cultures were associated with maternal bacteremia (P = 0.017) and neonatal EOS (P = 0.003). Prolonged ROM ≥18 h was associated with increased risk for Enterobacteriaceae‐positive cultures, while intrapartum ampicillin and gentamicin were associated with lower risk. Enterobacteriaceae‐positive compared with GBS‐positive birth cultures were associated with adverse maternal and neonatal outcomes. Conclusion: Positive birth cultures were related to maternal bacteremia and neonatal sepsis. Adverse outcomes were more prevalent among women with Enterobacteriaceae‐positive versus GBS‐positive birth cultures. Prolonged ROM is a risk factor for Enterobacteriaceae‐positive birth cultures among women with PPF. Antibiotic prophylaxis treatment for prolonged ROM should be reconsidered. Synopsis: The increasing prevalence of ampicillin‐resistant Enterobacteriaceae was observed as a cause for chorioamnionitis. Women with prolonged rupture of membranes are at risk for Enterobacteriaceae‐positive birth cultures. [ABSTRACT FROM AUTHOR]

Accidental rupture of membranes (acROM), an insertion-related complication of the balloon catheter for labor induction, may prolong the duration of ruptured membranes. Prolonged rupture of membranes is associated with an increased risk of intra-uterine infection with possibly neonatal infection as result. Little is known about safety profiles of different catheters regarding the occurrence of these complications. This study compares the incidence of neonatal early-onset sepsis (EOS) and acROM in women receiving either silicone or latex balloon catheters. A retrospective cohort study was performed including 2200 women (silicone balloon catheter, n = 1100 vs. latex balloon catheter, n = 1100). The primary outcomes were the incidence of acROM, and suspected and proven neonatal EOS. Secondary outcomes were: prolonged rupture of membranes, intrapartum fever, pre- or postnatal neonatal exposure to antibiotics, and perinatal outcomes. A subgroup analysis was performed between women with and without acROM. No statistically significant difference with regard to suspected or proven EOS was seen between the silicone and latex groups. The acROM rate was significantly higher in the silicone group compared to the latex group (2.9 % and 0.3 %, p < 0.01). Prolonged rupture of membranes was significantly more common in the silicone group compared to the latex group (5.0 % and 2.4 %, p < 0.01), as was the use of intrapartum antibiotics (12.7 % and 9.6 %, p = 0.02). Neonates were significantly more often exposed to pre- or postnatal antibiotics in the silicone group compared to the latex group (17.6 % and 13.6 %, p = 0.01). Subgroup analysis showed significantly more suspected and proven neonatal EOS when catheter-insertion was complicated with acROM (11.4 % and 20.0 %), compared to cases without acROM (3.8 % and 2.5 %), irrespective of the type of catheter used. The use of silicone balloon catheters for labor induction results in higher rates of acROM, prolonged rupture of membranes and use of intrapartum antibiotics, compared to latex balloon catheters. No statistically significant differences were found in the occurrence of suspected or proven neonatal EOS, however neonates from the silicone group were more often exposed to pre- or postnatal antibiotics. When acROM occurs, irrespective of type of catheter used, suspected and proven neonatal EOS was seen more often. [ABSTRACT FROM AUTHOR]

Abstract Background In Uganda, sepsis is the third-leading cause of neonatal deaths. Neonatal sepsis can be early-onset sepsis (EOS), which occurs ≤ 7 days postpartum and is usually vertically transmitted from the mother to newborn during the intrapartum period, or late-onset sepsis (LOS), occurring 8–28 days postpartum and largely acquired from the hospital environment or community. We described trends and spatial distribution of neonatal sepsis in Uganda, 2016–2020. Methods We conducted a descriptive incidence study using routinely-reported surveillance data on in-patient neonatal sepsis from the District Health Information System version 2 (DHIS2) during 2016–2020. We calculated incidence of EOS, LOS, and total sepsis as cases per 1,000 live births (LB) at district (n = 136), regional (n = 4), and national levels, as well as total sepsis incidence by health facility level. We used logistic regression to evaluate national and regional trends and illustrated spatial distribution using choropleth maps. Results During 2016–2020, 95,983 neonatal sepsis cases were reported, of which 71,262 (74%) were EOS. Overall neonatal sepsis incidence was 17.4/1,000 LB. EOS increased from 11.7 to 13.4 cases/1,000 LB with an average yearly increase of 3% (p

Abstract Background Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis. Methods We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains. Results Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R2 = 0.017, p = 0.001) and postnatal age (R2 = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p

Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria.

Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of culture-proven EOS in The Netherlands. In this retrospective study from 2019 to 2021, data were collected from 15 Dutch hospitals, comprising 13 regional hospitals equipped with Level I-II facilities and 2 academic hospitals equipped with Level IV facilities. Data included birth rates, number of neonates started on antibiotics for suspected EOS, number of neonates that continued treatment beyond 48 h and number of neonates with culture-proven EOS. Additionally, blood culture results were documented. Data were analysed both collectively and separately for regional and academic hospitals. A total of 103,492 live-born neonates were included. In 4755 neonates (4.6%, 95% CI 4.5–4.7), antibiotic therapy was started for suspected EOS, and in 2399 neonates (2.3%, 95% CI 2.2–2.4), antibiotic treatment was continued beyond 48 h. Incidence of culture-proven EOS was 1.1 cases per 1000 live births (0.11%, 95% CI 0.09–0.14). Overall, for each culture-proven EOS case, 40.6 neonates were started on antibiotics and in 21.7 neonates therapy was continued. Large variations in treatment rates were observed across all hospitals, with the number of neonates initiated and continued on antibiotics per culture-proven EOS case varying from 4 to 90 and from 4 to 56, respectively. The high number of antibiotic prescriptions compared to the EOS incidence and wide variety in clinical practice among hospitals in The Netherlands underscore both the need and potential for a novel approach to the management of neonates with suspected EOS.

Background: Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis. Methods: We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains. Results: Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R2 = 0.017, p = 0.001) and postnatal age (R2 = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria. Conclusions: Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants. [ABSTRACT FROM AUTHOR]

Background: In Uganda, sepsis is the third-leading cause of neonatal deaths. Neonatal sepsis can be early-onset sepsis (EOS), which occurs ≤ 7 days postpartum and is usually vertically transmitted from the mother to newborn during the intrapartum period, or late-onset sepsis (LOS), occurring 8–28 days postpartum and largely acquired from the hospital environment or community. We described trends and spatial distribution of neonatal sepsis in Uganda, 2016–2020. Methods: We conducted a descriptive incidence study using routinely-reported surveillance data on in-patient neonatal sepsis from the District Health Information System version 2 (DHIS2) during 2016–2020. We calculated incidence of EOS, LOS, and total sepsis as cases per 1,000 live births (LB) at district (n = 136), regional (n = 4), and national levels, as well as total sepsis incidence by health facility level. We used logistic regression to evaluate national and regional trends and illustrated spatial distribution using choropleth maps. Results: During 2016–2020, 95,983 neonatal sepsis cases were reported, of which 71,262 (74%) were EOS. Overall neonatal sepsis incidence was 17.4/1,000 LB. EOS increased from 11.7 to 13.4 cases/1,000 LB with an average yearly increase of 3% (p < 0.001); LOS declined from 5.7 to 4.3 cases/1,000 LB with an average yearly decrease of 7% (p < 0.001). Incidence was highest at referral hospitals (68/1,000 LB) and lowest at Health Center IIs (1.3/1,000 LB). Regionally, total sepsis increased in Central (15.5 to 23.0/1,000 LB, p < 0.001) and Northern regions (15.3 to 22.2/1,000 LB, p < 0.001) but decreased in Western (23.7 to 17.0/ 1,000 LB, p < 0.001) and Eastern (15.0 to 8.9/1,000, p < 0.001) regions. Conclusion: The high and increasing incidence of EOS in Uganda suggests a major gap in sepsis prevention and quality of care for pregnant women. The heterogenous distribution of neonatal sepsis incidence requires root cause analysis by health authorities in regions with consistently high incidence. Strengthening prevention and treatment interventions in Central and Northern regions, and in the most affected districts, could reduce neonatal sepsis. Employment of strategies which increase uptake of safe newborn care practices and prevent neonatal sepsis, such as community health worker (CHW) home visits for mothers and newborns, could reduce incidence. [ABSTRACT FROM AUTHOR]

Background and Aim: Neonatal sepsis is a systemic inflammatory response to infection during the first 4 weeks of an infant's life. It is a significant cause of neonatal morbidity and mortality in low‐ and middle‐income countries. This study aimed to determine the predictors of the onset of sepsis at the Neonatal Intensive Care Unit of the Tamale Teaching Hospital, Ghana. Methods: A cross‐sectional study was conducted among 275 mothers and their singleton neonates diagnosed clinically with sepsis. A univariate and multivariate logistic regression analysis adjusted for maternal occupational status was performed to determine the maternal and neonatal predictors of early‐onset (EOS) and late‐onset sepsis (LOS), respectively. Results: Single motherhood (AOR = 1.882, 95% CI = 0.926−3.822, p =.08) and home delivery (AOR = 3.667, 95% CI = 0.584−23.026, p =.17) were predictors of EOS, with single motherhood being the predictor for LOS (AOR = 2.906, 95% CI = 0.715−11.805, p =.14) in a univariate analysis. When maternal occupation was adjusted for in a multivariate analysis, single mother (AOR = 2.167, 95% CI = 1.010−4.648, p =.04) was the main predictor of EOS, with low neonatal birth weight being the main predictor of LOS (AOR = 0.193, 95% CI = 0.038−0.971, p =.04). Conclusion: Maternal marital status is a significant predictor of both EOS and LOS, with predictors of EOS being lower gestational age and low birth weight, while for LOS, low birth weight is the main predictor. Findings from this study can serve as a commencement point for developing predictive models for the onset of sepsis in neonates in the study facility. Key points: What is known: Neonatal sepsis is a medical emergency. What is new: Predictors for the identification of early and late‐onset sepsis in a resource‐poor setting have been identified in this study. The clinical implications of this study: Findings from this provide a valuable reference for the early identification of neonatal sepsis to improve clinical outcomes. Also, the findings in this study will serve as a commencement point for developing predictive models for identifying the onset of sepsis in neonates in resource‐poor settings in Sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

Prior studies demonstrated the neonatal early-onset sepsis (EOS) calculator's potential in drastically reducing antibiotic prescriptions, and its international adoption is increasing rapidly. To optimize the EOS calculator's impact, successful implementation is crucial. This study aimed to identify key barriers and facilitators to inform an implementation strategy. A multicenter cross-sectional survey was carried out among physicians, residents, nurses and clinical obstetricians of thirteen Dutch hospitals. Survey development was prepared through a literature search and stakeholder interviews. Data collection and analysis were based on the Consolidated Framework for Implementation Research (CFIR). A total of 465 stakeholders completed the survey. The main barriers concerned the expectance of the department's capacity problems and the issues with maternal information transfer between departments. Facilitators concerned multiple relative advantages of the EOS calculator, including stakeholder education, EOS calculator integration in the electronic health record and existing positive expectations about the safety and effectivity of the calculator. Based on these findings, tailored implementation interventions can be developed, such as identifying early adopters and champions, conducting educational meetings tailored to the target group, creating ready-to-use educational materials, integrating the EOS calculator into electronic health records, creating a culture of collective responsibility among departments and collecting data to evaluate implementation success and innovation results. [ABSTRACT FROM AUTHOR]

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Neonatal sepsis is a clinical syndrome mainly associated with a bacterial infection leading to severe clinical manifestations that could be associated with fatal sequalae. According to the time of onset, neonatal sepsis is categorized as early- (EOS) or late-onset sepsis (LOS). Despite blood culture being the gold standard for diagnosis, it has several limitations, and early diagnosis is not immediate. Consequently, most infants who start empirical antimicrobial therapy do not have an underlying infection. Despite stewardship programs partially reduced this negative trend, in neonatology, antibiotic overuse still persists, and it is associated with several relevant problems, the first of which is the increase in antimicrobial resistance (AMR). Starting with these considerations, we performed a narrative review to summarize the main findings and the future prospects regarding antibiotics use to treat neonatal sepsis. Because of the impact on morbidity and mortality that EOS and LOS entail, it is essential to start an effective and prompt treatment as soon as possible. The use of targeted antibiotics is peremptory as soon as the pathogen in the culture is detected. Although prompt therapy is essential, it should be better assessed whether, when and how to treat neonates with antibiotics, even those at higher risk. Considering that we are certainly in the worrying era defined as the “post-antibiotic era”, it is still essential and urgent to define novel strategies for the development of antibacterial compounds with new targets or mechanisms of action. A future strategy could also be to perform well-designed studies to develop innovative algorithms for improving the etiological diagnosis of infection, allowing for more personalized use of the antibiotics to treat EOS and LOS.

Abstract Background and Aim Neonatal sepsis is a systemic inflammatory response to infection during the first 4 weeks of an infant's life. It is a significant cause of neonatal morbidity and mortality in low‐ and middle‐income countries. This study aimed to determine the predictors of the onset of sepsis at the Neonatal Intensive Care Unit of the Tamale Teaching Hospital, Ghana. Methods A cross‐sectional study was conducted among 275 mothers and their singleton neonates diagnosed clinically with sepsis. A univariate and multivariate logistic regression analysis adjusted for maternal occupational status was performed to determine the maternal and neonatal predictors of early‐onset (EOS) and late‐onset sepsis (LOS), respectively. Results Single motherhood (AOR = 1.882, 95% CI = 0.926−3.822, p = .08) and home delivery (AOR = 3.667, 95% CI = 0.584−23.026, p = .17) were predictors of EOS, with single motherhood being the predictor for LOS (AOR = 2.906, 95% CI = 0.715−11.805, p = .14) in a univariate analysis. When maternal occupation was adjusted for in a multivariate analysis, single mother (AOR = 2.167, 95% CI = 1.010−4.648, p = .04) was the main predictor of EOS, with low neonatal birth weight being the main predictor of LOS (AOR = 0.193, 95% CI = 0.038−0.971, p = .04). Conclusion Maternal marital status is a significant predictor of both EOS and LOS, with predictors of EOS being lower gestational age and low birth weight, while for LOS, low birth weight is the main predictor. Findings from this study can serve as a commencement point for developing predictive models for the onset of sepsis in neonates in the study facility.

Abstract Introduction Globally, neonatal mortality is decreasing, and road maps such as the Early Newborn Action Plan set ambitious targets for 2030. Despite this, deaths in the first weeks of life continue to rise as a percentage of total child mortality. Neonatal sepsis with early onset continues to be a significant cause of death and illness. The majority of sepsis-related deaths occur in developing nations, where the prevalence and causes of newborn sepsis are yet unknown. As a result, the goal of this study was to determine the prevalence of early-onset sepsis and identify determinant factors. Methods A cross-sectional study was conducted on 368 study participants in referral hospitals of East and West Gojjam Zones from March 1st to April 30th, 2019. Study participants were selected at random using lottery method. Face-to-face interviews with index mothers for maternal variables and neonatal record review for neonatal variables were used to collect data using a structured pretested questionnaire. Data were entered into Epidata 3.1 and then exported to STATA/SE software version 14. Finally, the logistic regression model was used for analysis. Statistical significance was declared at P 18 h after rupture of membranes (AOR: 11.3, 95% CI: 3.0—41.8), gestational age of 32–37 weeks (AOR: 3.2, 95% CI: 1.2—8.5), and neonates who require resuscitation at birth (AOR: 4, 95% CI: 1.4 -11.8) were all found to be significantly associated with early-onset neonatal sepsis. Conclusion and recommendation Early-onset neonatal sepsis was found to be high in this study. Early-onset neonatal sepsis was found to be associated with maternal, obstetric, and neonatal variables. Comprehensive prevention strategies that target the identified risk factors should be implemented right away.

Early-onset sepsis (EOS) is a serious and fatal illness in neonates, Group B Streptococcus and Escherichia coli are major causative pathogens. We report a case of EOS and pneumonia caused by E. coli in a preterm neonate with multiple pneumatoceles and lung abscesses. A male neonate weighing 1670g was delivered at 33 6/7 weeks' gestation by a mother with clinical chorioamnionitis. He showed respiratory distress soon after birth and developed septic shock. He was intubated and mechanical ventilation was started. E.coli was detected in blood culture obtained from both the patient and his mother. He developed multiple pneumatoceles and lung abscesses. Surgical drainage was complicated, cefotaxime was thus continued until day 74. Pneumatoceles and lung abscesses are complications of neonatal pneumonia, rarely reported by E. coli. Multiple lung abscesses in our patient are distinct from single abscesses in previous case studies of neonatal lung abscesses. We speculate that bacteremia along with pneumatoceles led to multiple lung abscesses in our patient. These complications require long-term antibiotic therapy, to minimize morbidity and mortality, and should thus be considered when managing EOS caused by E. coli. [ABSTRACT FROM AUTHOR]

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003–2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond. [ABSTRACT FROM AUTHOR]

Aim: To examine whether biochemical surveillance vs clinical observation of term infants with prolonged rupture of membranes as a risk factor for early‐onset sepsis is associated with differences in patient trajectories in maternity and neonatal intensive care units. Methods: A retrospective study of live‐born infants with gestational age ≥ 37 + 0 weeks born after prolonged rupture of membranes (≥24 h) in four Norwegian hospitals 2017–2019. Two hospitals used biochemical surveillance, and two used predominantly clinical observation to identify early‐onset sepsis cases. Results: The biochemical surveillance hospitals had more C‐reactive protein measurements (p < 0.001), neonatal intensive care unit admissions (p < 0.001) and antibiotic treatment (p < 0.001). Hospitals using predominantly clinical observation initiated antibiotic treatment earlier in infants with suspected early‐onset sepsis (p = 0.04) but not in infants fulfilling early‐onset sepsis diagnostic criteria (p = 0.09). There was no difference in antibiotic treatment duration (p = 0.59), fraction of infants fulfilling early‐onset sepsis diagnostic criteria (p = 0.49) or length of hospitalisation (p = 0.30), and no early‐onset sepsis‐related adverse outcomes. Conclusion: The biochemical surveillance hospitals had more C‐reactive protein measurements, but there was no difference in antibiotic treatment duration, early‐onset sepsis cases, length of hospitalisation or adverse outcomes. Personnel resources needed for clinical surveillance should be weighed against the limitation of potentially painful procedures. [ABSTRACT FROM AUTHOR]

Antibiotics are the most frequently prescribed drugs in neonatal intensive care units (NICUs) due to the severity of complications accompanying neonatal sepsis. However, antimicrobial drugs are often used inappropriately due to the difficulties in diagnosing sepsis in the neonatal population. The reckless use of antibiotics leads to the development of resistant strains, rendering multidrug-resistant pathogens a serious problem in NICUs and a global threat to public health. The aim of this narrative review is to provide a brief overview of neonatal sepsis and an update on the data regarding indications for antimicrobial therapy initiation, current guidance in the empirical antimicrobial selection and duration of therapy, and indications for early discontinuation. [ABSTRACT FROM AUTHOR]

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a two-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 h of blood culture incubation (IQR 8–20), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which were Streptococcus epidermidis in neonates with LOS, and there was one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay. [ABSTRACT FROM AUTHOR]

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum and hematological biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM) and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided into two groups: group A, with PROM ≥ 18 h, and group B, with ROM < 18 h. Both groups were further split into subgroups: proven sepsis, presumed sepsis, and no sepsis. Descriptive statistics, analysis of variance (ANOVA) and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cell count from the first (p = 0.005) and third day (p = 0.028), and high C-reactive protein (CRP) values from the first day (p = 0.004). Procalcitonin (area under the curve—AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early-onset neonatal sepsis. (4) Conclusions: Our results outline the feasibility of using procalcitonin and CRP measured on the first day taken individually in order to increase the detection rate of early-onset neonatal sepsis, in the absence of positive blood culture.

(1) Background: Interleukin-6 (IL-6) levels act as an early infection marker preceding C-reactive protein (CRP) elevation. This study seeks to analyze IL-6 behavior in suspected early-onset sepsis (EOS) cases among term newborns, comparing it to that of CRP and evaluating IL-6’s diagnostic utility. We also aim to assess the impact of maternal risk factors on EOS in term newborns, quantifying their influence for informed decision making. (2) Methods: The retrospective data analysis included 533 term newborns who were admitted to our hospital because of suspected EOS. IL-6, CRP, and the impact of maternal risk factors were analyzed in the context of EOS using binomial test, Chi-squared test, logistic and linear regression. (3) Results: In the cases of EOS, both IL-6 and CRP were elevated. The increase in CRP can be predicted by the initial increase in IL-6 levels. Among the assessed risk factors, intrapartum maternal fever (adjusted odds ratio 18.1; 95% CI (1.7–4.1)) was identified as the only risk factor significantly associated with EOS. (4) Conclusions: Employing IL-6 as an early infection marker enhanced EOS diagnostic precision due to its detectable early rise. However, caution is required, as elevations in IL-6 and CRP levels do not exclusively indicate EOS. Increased CRP levels in healthy newborns with maternal risk factors may be attributed to dynamics of vaginal labor.

Background: Neonatal sepsis is regarded as one of the major health problems throughout the world. Neutrophil to Lymphocyte ratio [NLR] ratios as well as Platelet to Lymphocyte ratio [PLR] are simple, low cost and easily calculated biomarkers that may be employed for earlier diagnosing of neonatal sepsis. Aim of the work: The present study aims for the assessment of the Platelet to Lymphocyte ratio [PLR] as well as the Neutrophil to Lymphocyte ratio [NLR] in full-term neonates with early-onset sepsis [EOS], and its impact on management.Patients and Methods: The study involved 50 full-term neonates divided into two groups; patients’ group included 30 full-term neonates, diagnosed with EOS [positive blood culture] compared with control group which included 20 healthy full-term neonates.Results: The study showed no significant difference between cases and controls as regards demographic data. Patients with early-onset sepsis showed significant elevation of absolute neutrophil counts, NLR, PLR, C-reactive protein, in comparison with the control group. Positive predictive value [PPV] of NLR was 99%, PLR was 73%.Conclusion: NLR and PLR are predictive reliable markers in diagnosing and detecting early onset neonatal sepsis. NLR and PLR showed higher specificity results compared to CRP.

To investigate the diagnostic value of globulin (GLB) level, platelet count ( PLT),and their combination in premature infant with early-onset sepsis (EOS). Methods A total of 365 premature infants admitted to Shiyan Renmin Hospital from January 2017 to December 2021 were selected. A total of 113 infants diagnosed with EOS were selected as the study group, and 252 non-septicemic children with no signs of infection were selected as the control group. Clinical data of the two groups were retrospectively analyzed to explore the diagnostic value of GLB level and PLT in premature infants with EOS. Results The mean birth weight, gestational age, GLB level, album in (ALB) level, and PLT of the infants in the study group were significantly lower than those in the control group, with statistical significance (P < 0.05), and very low birth weight (< 1500 g),low gestational age (≤34 weeks), low GLB level, low ALB level, and low PLT are risk factors for EOS in premature infants. The receiver operating characteristic curve analysis showed that when the GLB level was lower than 15.55g/L, and the PLT was lower than 264.5×109 L-1, it was suggestive for the diagnosis of EOS; the sensitivity of GLB level to the diagnosis of EOS (48.4%) and The specificity (76.1%) was higher than the sensitivity (45.6%) and specificity (73.5%) of PLT. The combined detection of PLT and GLB levels (AUC=0.683) was more valuable in the diagnosis of EOS than the two alone. Conclusion The combined detection of GLB level and PLT is helpful for the early diagnosis of EOS in premature infants, and has a high reference value for clinical diagnosis. [ABSTRACT FROM AUTHOR]

Background: Group B streptococcus (GBS) harbors many virulence factors but there is limited data regarding their importance in colonization in pregnancy and early-onset disease (EOD) in the newborn. We hypothesized that colonization and EOD are associated with different distribution and expression of virulence factors. Methods: We studied 36 GBS EOD and 234 GBS isolates collected during routine screening. Virulence genes (pilus-like structures-PI-1, PI-2a, PI-2b; rib and hvgA) presence and expression were identified by PCR and qRT-PCR. Whole genome sequencing (WGS) and comparative genomic analyses were used to compare coding sequences (CDSs) of colonizing and EOD isolates. Results: Serotype III (ST17) was significantly associated with EOD and serotype VI (ST1) with colonization. hvgA and rib genes were more prevalent among EOD isolates (58.3 and 77.8%, respectively; p < 0.01). The pilus loci PI-2b and PI-2a were more prevalent among EOD isolates (61.1%, p < 0.01), while the pilus loci PI-2a and PI-1 among colonizing isolates (89.7 and 93.1% vs. 55.6 and 69.4%, p < 0.01). qRT PCR analysis revealed that hvgA was barely expressed in colonizing isolates, even though the gene was detected. Expression of the rib gene and PI-2b was two-fold higher in EOD isolates compared to colonizing isolates. Transcription of PI-2a was three-fold higher in colonizing isolates compared to EOD isolates. ST17 isolates (associated with EOD) had a smaller genome size compared ST1 and the genome was more conserved relative to the reference strain and ST17 isolates. In a multivariate logistic regression analysis virulence factors independently associated with EOD were serotype 3, and PI-1 and PI-2a was protective. Conclusion: There was a significant difference in the distribution of hvg A, rib, and PI genes among EOD (serotype III/ST17) and colonizing (serotype VI/ST1) isolates suggesting an association between invasive disease and these virulence factors. Further study is needed to understand the contribution of these genes to GBS virulence. [ABSTRACT FROM AUTHOR]

Comparing with other diseases, early onset sepsis (EOS) is a global health concern in neonatal period for its high morbidity and mortality rates. In recent years, many studies have contributed to the figure out the expression patterns of circulating micro-RNAs (miRNAs) in different diseases and progressions, which could function as diagnostic biomarkers for EOS. The purpose of this study was to analyze the expression patterns of selected miRNAs and evaluate their diagnostic value for early detection and treatment. This was a prospective cross-sectional study conducted from 1 July 2021 to 30 June 2022. We collected surplus peripheral blood and demographic statistics of septic neonates and non-infected neonates during the first 24 h after delivery and obtained 11 candidate miRNAs by literature screening. First, we extracted the candidate miRNAs from the serum of selected neonates and analyzed their expression levels, and then the receiver operating characteristic (ROC) curve was used to select the differentially expressed miRNAs. We analyzed their sensitivity and specificity and obtained the best diagnostic panel. Finally, with the help of differentially expressed miRNAs, we performed gene ontology (GO) enrichment and protein–protein interaction (PPI) analyses by their target genes. In patients with EOS, three miRNAs (mir-223-3p, mir-15a-5p, and mir-17-5p) in serum were significantly downregulated, and mir-146a-5p, mir-1-3p, and mir-16-5p were upregulated. The diagnostic value of these miRNAs (miR-15a-5p, AUC = 0.67; miR-223-3p, AUC = 0.72; miR-16-5p, AUC = 0.68; miR‐17‐5p, AUC = 0.70; miR-1-3p, AUC = 0.69; miR‐146a‐5p, AUC = 0.72) was moderate, and the diagnostic panel constructed by miR-15a-5p, miR-223-3p, and miR-16-5p possessed a comparatively higher diagnostic value (AUC = 0.85, sensitivity: 74.6%, specificity: 86%), indicating that their combined application may be a promising biomarker for clinical diagnosis of EOS. According to GO enrichment analysis, most proteins encoded by target genes were located in the cytosol as for cellular component (CC), for molecular function (MF), most proteins acted as regulators in protein binding, and for biological process (BP). Most genes function in positive or negative regulation of transcription from RNA polymerase II promoter, and the top 10 hub genes were CDKN1A, YAP1, CCNE1, CCND1, CKK6, ERBB4, CHEK1, DICER1, VEGFA, and APP by rank degree after PPI construction. The three-miRNA panels (miR-15a-5p, miR-223-3p, and miR-16-5p) may be a novel noninvasive biological marker for EOS screening. [ABSTRACT FROM AUTHOR]

Introduction: Globally, neonatal mortality is decreasing, and road maps such as the Early Newborn Action Plan set ambitious targets for 2030. Despite this, deaths in the first weeks of life continue to rise as a percentage of total child mortality. Neonatal sepsis with early onset continues to be a significant cause of death and illness. The majority of sepsis-related deaths occur in developing nations, where the prevalence and causes of newborn sepsis are yet unknown. As a result, the goal of this study was to determine the prevalence of early-onset sepsis and identify determinant factors. Methods: A cross-sectional study was conducted on 368 study participants in referral hospitals of East and West Gojjam Zones from March 1st to April 30th, 2019. Study participants were selected at random using lottery method. Face-to-face interviews with index mothers for maternal variables and neonatal record review for neonatal variables were used to collect data using a structured pretested questionnaire. Data were entered into Epidata 3.1 and then exported to STATA/SE software version 14. Finally, the logistic regression model was used for analysis. Statistical significance was declared at P < 0.05 after multivariable logistic regression. Results: A total of 368 newborns and their index mothers took part in this study. The mean age of the newborns was 4.69 days (± 1.93SD). Early-onset neonatal sepsis was seen in 34% of the babies. Nulliparity (AOR: 3.3, 95% CI: 1.1–9.5), duration of labor > 18 h after rupture of membranes (AOR: 11.3, 95% CI: 3.0—41.8), gestational age of 32–37 weeks (AOR: 3.2, 95% CI: 1.2—8.5), and neonates who require resuscitation at birth (AOR: 4, 95% CI: 1.4 -11.8) were all found to be significantly associated with early-onset neonatal sepsis. Conclusion and recommendation: Early-onset neonatal sepsis was found to be high in this study. Early-onset neonatal sepsis was found to be associated with maternal, obstetric, and neonatal variables. Comprehensive prevention strategies that target the identified risk factors should be implemented right away. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Neonatal gentamicin dosing algorithms are not designed to achieve serum trough concentrations ≤1 mcg/mL. The purpose of our study was to evaluate a new gentamicin algorithm based on serum creatinine (SCr) and gestational age (GA) designed to achieve serum gentamicin trough concentrations ≤1 mcg/mL. METHODS: A retrospective cohort study was conducted in a level IIIB neonatal intensive care unit. The incidence of elevated serum gentamicin troughs for this study was compared with the center's previously published results to evaluate the proposed dosing algorithm. Patients were included if gentamicin was administered within the first 7 days of life and a serum gentamicin trough concentration and a baseline SCr concentration were obtained. Patients were further subdivided into groups based on GA for data analysis: ≤30 weeks (group 1), 30-34 weeks (group 2), and ≥35 weeks (group 3). The SCr was considered mildly elevated (0.81-0.99 mg/dL) or elevated (≥1 mg/dL). The respective outcomes between the post-algorithm and control groups were examined using intention-to-treat analysis and Bayesian modeling to calculate rate differences. RESULTS: Of the 2377 patients evaluated, 366 met the inclusion criteria. Significantly lower percentages of elevated serum gentamicin troughs were noted in groups 2 and 3 subsequent to the implementation of the dosing algorithm with 16% and 15% lower rate differences, respectively. Regardless of GA, there were significantly fewer elevated serum troughs in the post-implementation groups than in the control with mildly elevated and elevated SCr p < 0.001. CONCLUSIONS: Using a dosing algorithm based on SCr significantly reduced the number of elevated serum trough rates in neonates with a GA greater than 30 weeks. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of combined detection of serum procalcitonin (PCT), cytochrome C (Cyt-C), progranulin protein (PGRN) and arterial blood lactic acid in the diagnosis of neonatal early-onset sepsis (EOS), and analyze its relationship with poor prognosis in children. Methods: 115 children with EOS admitted to our hospital from February 2019 to June 2021 were selected as the EOS group, and 80 healthy newborns were selected as the control group during the same period. Serum PCT, Cyt-C, PGRN, and arterial blood lactic acid were compared between the two groups. The diagnostic value of serum PCT, Cyt-C, PGRN and arterial blood lactate on EOS was analyzed by receiver operating characteristic (ROC) curve. All children were followed up for 6 months after discharge, and were divided into a good prognosis group and a poor prognosis group according to their prognosis. Univariate and multivariate Logistic regression was used to analyze the risk factors of poor prognosis in children with EOS. Results: The levels of serum PCT, Cyt-C, PGRN and arterial blood lactic acid in the EOS group were significantly higher than those in the control group (P<0.05). ROC curve analysis showed that combined detection of serum PCT, Cyt-C, PGRN, and arterial blood lactate had high sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of EOS, and the area under the curve (AUC) was 0.836. The levels of serum PCT, Cyt-C, PGRN and arterial blood lactate in the poor prognosis group were significantly higher than those in the good prognosis group (P<0.05). The results of multivariate Logistic regression analysis showed that premature birth, low birth weight infants, pathological jaundice, intracranial infection, serum PCT≥8.32 ng/L, serum Cyt-C≥42.52 ng/mL, serum PGRN≥48.83 ng/mL, arterial Blood lactic acid ≥ 5.21 mmol/L was a risk factor for poor prognosis in children with EOS (P<0.05). Conclusion: The levels of serum PCT, Cyt-C, PGRN and arterial blood lactate are abnormally elevated in EOS neonates, and their combined detection has a high diagnostic value. Premature birth, low birth weight infants, pathological jaundice, intracranial infection, serum PCT, Cyt-C, PGRN, and arterial blood lactic acid are risk factors for poor prognosis in neonates with EOS. Attention should be paid to neonates with risk factors, and early adoption interventions to improve their prognosis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence, causative pathogens, morbidities, mortality, and risk factors associated with blood culture-positive early-onset sepsis (EOS, ≤72 hours of age) in symptomatic neonates admitted to the neonatal intensive care units (NICUs) of a middle-income country. Study Design: Retrospective cohort study using data submitted prospectively to the Malaysian National Neonatal Registry (MNNR). Setting: 44 Malaysian NICUs. Participants: All neonates born in 2015- 2020. Results: EOS was reported in 991 neonates. The annual incidence of EOS increased from 0.46 to 0.49/1000 livebirths over the six years. The most common pathogen was Streptococcus agalactiae or Group B haemolytic streptococcus (GBS) (n=388, 39.2%), followed by Escherichia coli (E. coli) (n=80, 8.1%), Klebsiella spp (n=73, 7.4%), coagulase negative staphylococcus (CONS) (n=73, 7.4%), Pseudomonas spp (n=44, 4.4%) and methicillin-sensitive Staphylococcus aureus (n=34, 3.4%). The incidence of EOS due to GBS increased from 0.17 to 0.22/1000 livebirths. Morbidities and mortality were higher in those with EOS than without EOS. Multiple logistic regression analysis showed that Indian ethnic group, chorioamnionitis, gestation≥37weeks, female, spontaneous vaginal delivery, instrumental delivery, and surfactant therapy were significantly associated with increased risk of EOS due to GBS. Four factors were significantly associated with increased risk of non-GBS EOS (outborns, birthweight <1000 g, vaginal delivery, and surfactant therapy). Early continuous positive airway pressure was associated with significantly lower risk of EOS. Conclusion: The incidence of EOS showed an increasing trend in Malaysian NICUs. GBS was the most common causative pathogen. Several modifiable risk factors associated with EOS have been identified. [ABSTRACT FROM AUTHOR]

Abstract Background Early diagnosis and prompt antibiotic treatment are crucial to reducing morbidity and mortality of early-onset sepsis (EOS) in neonates. However, this strategy remains challenging due to non-specific clinical findings and limited facilities. Inappropriate antibiotics use is associated with ineffective therapy and adverse outcomes. This study aims to determine the characteristics of EOS and use of antibiotics in the neonatal-intensive care units (NICUs) in Indonesia, informing efforts to drive improvements in the prevention, diagnosis, and treatment of EOS. Methods A descriptive study was conducted based on pre-intervention data of the South East Asia-Using Research for Change in Hospital-acquired Infection in Neonates project. Our study population consisted of neonates admitted within 72 h of life to the three participating NICUs. Neonates who presented with three or more clinical signs or laboratory results consistent with sepsis and who received antibiotics for 5 consecutive days were considered to have EOS. Culture-proven EOS was defined as positive blood or cerebrospinal fluid culture. Type and duration of antibiotics used were also documented. Results Of 2,509 neonates, 242 cases were suspected of having EOS (9.6%) with culture-proven sepsis in 83 cases (5.0% of neonatal admissions in hospitals with culture facilities). The causative organisms were mostly gram-negative bacteria (85/94; 90.4%). Ampicillin / amoxicillin and amikacin were the most frequently prescribed antibiotics in hospitals with culture facilities, while a third-generation cephalosporin was mostly administered in hospital without culture facilities. The median durations of antibiotic therapy were 19 and 9 days in culture-proven and culture-negative EOS groups, respectively. Conclusions The overall incidence of EOS and culture-proven EOS was high in Indonesia, with diverse and prolonged use of antibiotics. Prospective antibiotic surveillance and stewardship interventions are required.

Prior studies demonstrated the neonatal early-onset sepsis (EOS) calculator’s potential in drastically reducing antibiotic prescriptions, and its international adoption is increasing rapidly. To optimize the EOS calculator’s impact, successful implementation is crucial. This study aimed to identify key barriers and facilitators to inform an implementation strategy. A multicenter cross-sectional survey was carried out among physicians, residents, nurses and clinical obstetricians of thirteen Dutch hospitals. Survey development was prepared through a literature search and stakeholder interviews. Data collection and analysis were based on the Consolidated Framework for Implementation Research (CFIR). A total of 465 stakeholders completed the survey. The main barriers concerned the expectance of the department’s capacity problems and the issues with maternal information transfer between departments. Facilitators concerned multiple relative advantages of the EOS calculator, including stakeholder education, EOS calculator integration in the electronic health record and existing positive expectations about the safety and effectivity of the calculator. Based on these findings, tailored implementation interventions can be developed, such as identifying early adopters and champions, conducting educational meetings tailored to the target group, creating ready-to-use educational materials, integrating the EOS calculator into electronic health records, creating a culture of collective responsibility among departments and collecting data to evaluate implementation success and innovation results.

Background Sepsis is the most frequent cause of neonatal deaths globally, varying in incidence between different countries. Sepsis is a burden on families and health care resources. Objectives To identify prevalence, type of organism, and outcome of early-onset sepsis (EOS) and late-onset sepsis (LOS). Patients and methods A cross-sectional study was conducted at the neonatal ICU of Mataria Teaching Hospital from November 2018 to October 2019. Demographic, clinical, and laboratory data of proved septic neonates were collected. Classification of cases according to the onset of sepsis: EOS (group I), in which sepsis is presented clinically before the third day of life, and LOS (group II), in which sepsis presented clinically after the third day of life. The LOS is subsequently divided into hospital-acquired infection (nosocomial infection) (group IIa) and community-acquired infection group (group IIb). Results A total of 51 neonates were diagnosed as having sepsis, with a prevalence of 2.8% of total admitted neonates for EOS and 4.4% for LOS (3.7% for nosocomial and 0.7% for community-acquired infection). Vomiting, poor feeding, and respiratory distress were the commonest presenting symptoms in EOS and LOS. Blood transfusion is needed mostly in EOS. Gram-negative organisms were common in EOS and nosocomial infection, whereas gram-positive organisms were the commonest in community-acquired infection. Klebsiella was the commonest responsible organism for neonatal sepsis, which is sensitive to meropenem, imipenem, and ciprofloxacin. The total mortality rate was 25%, with no difference among the three groups. Conclusion Late onset sepsis (LOS) has a higher prevalence than early-onset one. Klebsiella was the commonest responsible organism for neonatal sepsis in our unit, and the most sensitive antibiotics are imipenem, meropenem, and ciprofloxacin regardless the onset of sepsis. Still neonatal sepsis has a high mortality rate irrespective of the onset of sepsis.

BackgroundGroup B streptococcus (GBS) harbors many virulence factors but there is limited data regarding their importance in colonization in pregnancy and early-onset disease (EOD) in the newborn. We hypothesized that colonization and EOD are associated with different distribution and expression of virulence factors.MethodsWe studied 36 GBS EOD and 234 GBS isolates collected during routine screening. Virulence genes (pilus-like structures-PI-1, PI-2a, PI-2b; rib and hvgA) presence and expression were identified by PCR and qRT-PCR. Whole genome sequencing (WGS) and comparative genomic analyses were used to compare coding sequences (CDSs) of colonizing and EOD isolates.ResultsSerotype III (ST17) was significantly associated with EOD and serotype VI (ST1) with colonization. hvgA and rib genes were more prevalent among EOD isolates (58.3 and 77.8%, respectively; p < 0.01). The pilus loci PI-2b and PI-2a were more prevalent among EOD isolates (61.1%, p < 0.01), while the pilus loci PI-2a and PI-1 among colonizing isolates (89.7 and 93.1% vs. 55.6 and 69.4%, p < 0.01). qRT PCR analysis revealed that hvgA was barely expressed in colonizing isolates, even though the gene was detected. Expression of the rib gene and PI-2b was two-fold higher in EOD isolates compared to colonizing isolates. Transcription of PI-2a was three-fold higher in colonizing isolates compared to EOD isolates. ST17 isolates (associated with EOD) had a smaller genome size compared ST1 and the genome was more conserved relative to the reference strain and ST17 isolates. In a multivariate logistic regression analysis virulence factors independently associated with EOD were serotype 3, and PI-1 and PI-2a was protective.ConclusionThere was a significant difference in the distribution of hvg A, rib, and PI genes among EOD (serotype III/ST17) and colonizing (serotype VI/ST1) isolates suggesting an association between invasive disease and these virulence factors. Further study is needed to understand the contribution of these genes to GBS virulence.

Aim: To determine the management perspective of early-onset neonatal sepsis among neonatologists from Lima – Perú and to compare it with international society guideline recommendations. Material and Methods: We collected data from August to December 2018 from 151 neonatologists working in neonatal units in Lima-Perú with an anonymous survey. The survey contained three questions related to the participant's general characteristics and eight questions regarding the management of early-onset sepsis, including the risk factors relating to the initiation of postnatal antibiotics, the management of a low-risk febrile neonate, laboratory cutoff values, indications for a lumbar puncture, and first-line therapy and antibiotic therapy duration in culture-proven and culture-negative sepsis. Results: The mean age of the participants was 46.2 ± 8.1 years, with a median duration of clinical practice of 6 years (4.0 – 12.0). Chorioamnionitis (76.2%), maternal fever (62.3%) and prolonged rupture of the membranes (52.3%) were the most common risk factors considered for postnatal antibiotic therapy. Of the participants, 91.4% would not prescribe antibiotic therapy for a low-risk febrile neonate and would, instead, track the fever (82.8%) and do a sepsis workup (65.6%). In addition, 97.4% would do a lumbar puncture in a neonate with seizures and EOS. Only 43.1% would do a lumbar puncture in cases with a positive blood culture. Of the neonatologist, 98% defined leukopenia as a leukocyte count ≤5 × 109/L and 47.7% defined leukocytosis as a count of ≥25 × 109/L. An immature to total neutrophil ratio of ≥0.20 was used by 57.6% of them. Ampicillin/amikacin is the most common first-line drug combination for EOS, followed by ampicillin/gentamicin and ampicillin/cefotaxime. Median duration of antibiotic therapy for Gram-positive and Gram-negative organisms is 7 days (7.0 – 10.0) and 10 days (10.0 – 14.0), respectively. In culture-negative early-onset sepsis, the median antibiotic therapy duration is 7 days (5.0 – 7.0). Conclusion: There are significant differences in the approach to and management of EOS among neonatologists from Lima – Perú. A local standardized protocol would prevent this variability and minimize unnecessary procedures, antibiotic exposure, bacterial resistance, prolonged hospital stay, and mother-newborn separation.