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Background: Early-onset neonatal sepsis (EOS) is a rare condition but an important cause of severe morbidity and mortality in neonates., Methods: This is a prospective observational study in neonates born at ≥34 weeks of gestation (WG). The primary endpoint was EOS, defined by isolation of pathogenic species from blood culture and/or cerebrospinal fluid culture within 72 hours after birth. Data on EOS were collected exhaustively from all maternity wards in Paris area (April 2019-March 2021)., Results: 108 EOS were recorded (annual incidence, 0.32 per 1000 live births; 95% CI 0.26 to 0.38). In term infants, the most frequent pathogens were group B Streptococcus (GBS) (n=47) and Escherichia coli (n=20); in late preterm infants, the most frequent pathogens were E. coli (n=15) and GBS (n=7). Fifteen meningitis cases were diagnosed. Five E. coli strains (14%) were resistant to both amoxicillin and gentamicin, which is an empiric treatment for EOS. Of the 54 infants with GBS infections, 35 were born from mothers with negative GBS prepartum screening test and 8 from mothers with no screening. Two deaths were reported, both in term infants ( Proteus mirabilis and E. coli )., Conclusion: In neonates ≥34 WG born in the Paris area, GBS was twice as frequent as E. coli in term infants. EOS was six times more frequent in late preterm than in term infants and was due to E. coli in 60% of cases. Prevention of GBS EOS and empiric antibiotic treatment of EOS could be improved., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To evaluate the performance of serum amyloid-A (SAA), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein-A1 (Apo-A1) levels in the identification and monitoring of neonatal sepsis., Methods: This prospective study included 113 full-term septic neonates (postnatal age 4-28 days) admitted to the Special Care Neonatal Unit of a University Hospital from January 1, 2016, to April 30, 2019, and 68 healthy neonates (controls). Blood samples were drawn serially in septic neonates at enrollment and on days 1, 3 and 7, and once in controls, for SAA, HDL-C and Apo-A1 determination., Results: At enrollment, SAA levels were significantly higher in septic neonates in comparison with controls (median 50.7 vs. 3.5 mg/L; P < 0.0001); HDL-C and Apo-A1 levels were significantly lower in patients than in controls (P < 0.001 and P < 0.006, respectively). SAA levels were higher in culture-positive compared with culture-negative sepsis (median 202.0 vs. 14.2 mg/L; P < 0.0001). HDL-C and Apo-A1 levels did not differ significantly between culture-positive and culture-negative sepsis. Receiver operating characteristic curve analysis of SAA levels at enrollment resulted in significant areas under the curve (AUC) for detecting sepsis {AUC = 0.929 [95% confidence interval: 0.885-0.973]; P < 0.0001} and also for discriminating between culture-positive and culture-negative sepsis [AUC = 0.933 (95% confidence interval: 0.882-0.984); P < 0.0001]. The combination of HDL-C and Apo-A1 with SAA increased its diagnostic performance. Furthermore, serial SAA levels following enrollment could indicate clinical response in septic neonates., Conclusions: SAA seems to be a useful biomarker for identification and monitoring of neonatal sepsis, and also for discriminating between culture-positive and culture-negative sepsis. HDL-C and Apo-A1 could be used as complementary markers.

Neonatal sepsis is a catastrophic condition of global concern, with reported mortality rates exceeding 10%. Bloodstream infections are an important cause of sepsis, and epidemiological studies of these infections are crucial for predicting the most common aetiological agents and antimicrobial susceptibility patterns and for developing antimicrobial guidelines. For the ten-year study period from July 2013 to June 2023, all neonatal bacteraemia cases were reviewed prospectively using an enhanced surveillance protocol. The patients were stratified according to their age at the time of blood culture collection: early onset if diagnosed in the first 72 hours of life, and late onset if diagnosed after that time. During the study period, 170 blood cultures were positive from 144 patients, of which 89 specimens from 64 patients represented the growth of significant pathogens. Coagulase-negative staphylococci (CoNS) were the most common pathogens identified (52%, 33/64), followed by Escherichia coli (14%, 9/64), Group B Streptococcus (GBS: 11%, 7/64) and Staphylococcus aureus (11%, 7/64). GBS was more commonly identified in early onset patients, while CoNS were predominantly associated with late onset. The presence of an intravascular catheter, maternal urinary tract infections and the receipt of total parenteral nutrition or transfused blood were identified as significant risk factors. The fatality rate was 8% (5/64). in summary, this study provides a detailed overview of the epidemiology of neonatal bacteraemia in a large teaching hospital in the Midwest of Ireland over a decade. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is associated with neurocognitive impairment among preterm neonates but less is known about term neonates with sepsis. This systematic review and meta-analysis aims to provide an update of neurocognitive outcomes including cognitive delay, visual impairment, auditory impairment, and cerebral palsy, among neonates with sepsis. Methods: We performed a systematic review of PubMed, Embase, CENTRAL and Web of Science for eligible studies published between January 2011 and March 2023. We included case–control, cohort studies and cross-sectional studies. Case reports and articles not in English language were excluded. Using the adjusted estimates, we performed random effects model meta-analysis to evaluate the risk of developing neurocognitive impairment among neonates with sepsis. Results: Of 7,909 studies, 24 studies (n = 121,645) were included. Majority of studies were conducted in the United States (n = 7, 29.2%), and all studies were performed among neonates. 17 (70.8%) studies provided follow-up till 30 months. Sepsis was associated with increased risk of cognitive delay [adjusted odds ratio, aOR 1.14 (95% CI: 1.01—1.28)], visual impairment [aOR 2.57 (95%CI: 1.14- 5.82)], hearing impairment [aOR 1.70 (95% CI: 1.02–2.81)] and cerebral palsy [aOR 2.48 (95% CI: 1.03–5.99)]. Conclusion: Neonates surviving sepsis are at a higher risk of poorer neurodevelopment. Current evidence is limited by significant heterogeneity across studies, lack of data related to long-term neurodevelopmental outcomes and term infants. [ABSTRACT FROM AUTHOR]

The threshold for a late-onset sepsis (LOS) evaluation varies considerably across NICUs. This unexplained variability is probably related in part to physician bias regarding when sepsis should be "ruled out". The aim of this study is to determine if physician characteristics (race, gender, immigration status, years of experience and academic rank) effect LOS evaluation in the NICU. This study includes a retrospective chart review of all Level III NICU infants who had a LOS evaluation over 54 months. Physician characteristics were compared between positive and negative blood culture groups and whether CBC and CRP were obtained at LOS evaluations. There were 341 LOS evaluations performed during the study period. Two patients were excluded due to a contaminant. Patients in this study had a birth weight of [median (Q1, Q3)]+ 992 (720, 1820) grams and birth gestation of [median (Q1, Q3)] 276/7 (252/7, 330/7) weeks. There are 10 neonatologists in the group, 5/10 being female and 6/10 being immigrant physicians. Experienced physicians were more likely to obtain a CBC at the time of LOS evaluation. Physician characteristics of race, gender and immigration status impacted whether to include a CRP as part of a LOS evaluation but otherwise did not influence LOS evaluation, including the likelihood of bacteremia. [ABSTRACT FROM AUTHOR]

(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case–control study included infants with birth weight < 1500 g and/or gestational age ≤ 30 weeks. Short-term outcomes, brain MRI findings, and severe functional disability (SFD) at age 24 months were compared between infants with culture-proven or culture-negative sepsis or without sepsis. A chi-squared test or Mann–Whitney U test was used to compare the clinical and instrumental characteristics and the outcomes between cases and controls. (3) Results: Infants with sepsis (all sepsis n = 76; of which culture-proven n = 33 and culture-negative n = 43) were matched with infants without sepsis (n = 76). Compared with infants without sepsis, both all sepsis and culture-proven sepsis were associated with SFD. In multivariate logistic regression analysis, SFD was associated with intraventricular hemorrhage (OR 4.7, CI 1.7–13.1, p = 0.002) and all sepsis (OR 3.68, CI 1.2–11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority. [ABSTRACT FROM AUTHOR]

Neonatal sepsis causes significant global morbidity and mortality, with the highest burden in resource-limited settings where 99% of neonatal deaths occur. There are multiple challenges to achieving successful treatment of neonates in this setting. Firstly, reliable and low-cost strategies for risk identification are urgently needed to facilitate treatment as early as possible. Improved laboratory capacity to allow identification of causative organisms would support antimicrobial stewardship. Antibiotic treatment is still hampered by availability, but also increasingly by antimicrobial resistance – making surveillance of organisms and judicious antibiotic use a priority. Finally, supportive care is key in the management of the neonate with sepsis and has been underrecognized as a priority in resource-limited settings. This includes fluid balance and nutritional support in the acute phase, and follow-up care in order to mitigate complications and optimise long-term outcomes. There is much more work to be done in identifying the holistic needs of neonates and their families to provide effective family-integrated interventions and complete the package of neonatal sepsis management in resource-limited settings. [ABSTRACT FROM AUTHOR]

The mechanism of long-term cognitive impairment after neonatal sepsis remains poorly understood, although long-lasting neuroinflammation has been considered the primary contributor. Necroptosis is actively involved in the inflammatory process, and in this study, we aimed to determine whether neonatal sepsis-induced long-term cognitive impairment was associated with activation of necroptosis. Rat pups on postnatal day 3 (P3) received intraperitoneal injections of lipopolysaccharide (LPS, 1 mg/kg) to induce neonatal sepsis. Intracerebroventricular injection of IL-1β-siRNA and necrostatin-1 (NEC1) were performed to block the production of IL-1β and activation of necroptosis in the brain, respectively. The Morris water maze task and fear conditioning test were performed on P28–P32 and P34–P35, respectively. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-PCR), and Western blotting were used to examine the expression levels of proinflammatory cytokines and necroptosis-associated proteins, such as receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Sustained elevation of IL-1β level was observed in the brain after initial neonatal sepsis, which would last for at least 32 days. Sustained necroptosis activation was also observed in the brain. Knockdown of IL-1β expression in the brain alleviated necroptosis and improved long-term cognitive function. Direct inhibition of necroptosis also improved neurodevelopment and cognitive performance. This research indicated that sustained activation of necroptosis via IL-1β contributed to long-term cognitive dysfunction after neonatal sepsis. [ABSTRACT FROM AUTHOR]

Objective: An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics. Patients and Methods: All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis. Results: ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184– 199.326, P< 0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009– 10.055, P< 0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis. Conclusion: E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility. [ABSTRACT FROM AUTHOR]

Background: The pathogen distribution and antibiotic susceptibility of the pathogens in early-onset sepsis (EOS) differ between countries. The epidemiological data from a limited number of studies about EOS in Turkey are insufficient. In this study, we aimed to evaluate the culture-proven EOS cases, causative microorganisms, antibiotic susceptibility patterns, and risk factors for mortality in EOS. Methods: This is a retrospective, single-center study over a 7-year period, from 2013 to 2020, at Zeynep Kamil Maternity and Children's Hospital, İstanbul, Turkey. Results: During the study period, 8229 newborns were admitted to our neonatal intensive care unit. Culture-proven EOS was detected in 101 patients (0.12%). Out of these, 56 (55.4%) were Gram-positive, and 45 (44.5%) were Gram-negative sepsis. The most common isolated organism was E. coli (28.7%, n = 29), followed by GBS (16.8%, n = 17) and S. aureus (15.8%, n = 16). An ampicillin and gentamicin combination had antimicrobial coverage in 92.6% of cases. Seventeen patients (16.8%) died because of EOS. Severe neutropenia was found to be an independent risk factor for mortality in EOS (p = 0.001, OR = 14.4, CI 95%: 2.8–74). Conclusions: Although the majority of causative agents were Gram-positive (55.4%), the most common isolated organism was E. coli. An empirical antibiotic regimen of ampicillin and gentamicin continues to have an adequate coverage for EOS in our population. [ABSTRACT FROM AUTHOR]

Neonatal sepsis is an important risk factor for lesions in the brain of preterm newborns (PTNB) and the most effective strategies to minimize its deleterious effects are early detection and intervention. To investigate the presence of neurological abnormalities in PTNBs after neonatal sepsis. This was a prospective cross-sectional study with 100 PTNBs selected at random, 50 of the study group (sepsis) and 50 of the control group (non-sepsis). The neurological evaluation protocol adopted was the Hammersmith Neonatal Neurological Examination (HNNE). The PTNBs of the sepsis group had total HNNE scores lower than expected for normality in 86% of the cases, and the non-sepsis group in 26% (p <.001). Higher prevalence levels of altered scores in tone category (p <.001), tone patterns (p =.026), reflexes (p =.002), movements (p <.001), abnormal signs (p <.001) and behavior (p <.001). The neurological dysfunctions after neonatal sepsis could be identified by clinical neonatal neurological evaluation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to investigate etiological agents, patterns of antimicrobial resistance and predictors of mortality in culture proven neonatal sepsis. METHOD: This is a twenty-four month retrospective cohort study of infants with culture proven sepsis. Demographic data, type of isolates and its sensitivity pattern were recorded. Multidrug resistant gram-negative isolates were defined as resistance to any three of five antibiotic classes: extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones and piperacillin-tazobactam. RESULT: A total of 183 case with culture positive sepsis were identified. Early onset sepsis occurred in 59% of cases. The majority of isolates (56.2%) were gram-positive but the most common individual isolates were klebsiella spp. (31.1%), Staphylococcus aureus (24.5%) and coagulase-negative staphylococci (CONS) (22.9%). The pathogen mix in early-onset did not differ from late-onset sepsis. High rates of multidrug resistance were observed in klebsiella spp. (49.1%), Escherichia coli (50%), citrobacter spp (50%), acinetobacter spp. (28.5%), pseudomonas spp. (100%) isolates. Methicillin resistance prevailed in 16.6% of coagulase-negative staphylococci, 24.4% of Staphylococcus aureus and 62.5% of enterococcus spp. Multivariate analysis revealed invasive ventilation and early onset sepsis to be independently associated with increased risk of mortality in contrast to breast milk feeding which is associated with decreased risk of mortality. CONCLUSION: A high degree of antimicrobial resistance underscores the need to understand the pathogenesis of resistance, curtail the irrational prescription of antibiotics in neonates and the requirement for measures to prevent it in low-income and middle-income countries. [ABSTRACT FROM AUTHOR]

Staphylococcus epidermidis accounts for the majority of cases of neonatal sepsis. Moreover, it has been demonstrated to be associated with neonatal morbidities, such as bronchopulmonary dysplasia (BPD), white matter injury (WMI), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP), which affect short-term and long-term neonatal outcome. Imbalanced inflammation has been considered to be a major underlying mechanism of each entity. Conventionally regarded as a harmless commensal on human skin, S. epidermidis has received less attention than its more virulent relative Staphylococcus aureus. Particularities of neonatal innate immunity and nosocomial environmental factors, however, may contribute to the emergence of S. epidermidis as a significant nosocomial pathogen. Neonatal host response to S. epidermidis sepsis has not been fully elucidated. Evidence is emerging regarding the implication of S. epidermidis sepsis in the pathogenesis of neonatal inflammatory diseases. This review focuses on the interplay among S. epidermidis, neonatal innate immunity and inflammation-driven organ injury. [ABSTRACT FROM AUTHOR]

The patients who received treatment for more than 48 h included two with clinical signs, elevated CRP and positive gastric aspirate cultures, who were treated for six and 10 days, respectively. Abbreviations EOS early-onset sepsis CRP C-reactive protein Early-onset sepsis (EOS) has been associated with a particularly high rate of mortality and morbidity in preterm neonates,1,2 and many patients receive empirical antibiotics at birth, regardless of whether they have an infection. Most clinicians followed a new protocol for managing early-onset sepsis for preterm infants, but a fifth of preterm infants received antibiotics for longer than necessary. [Extracted from the article]