BACKGROUND: The emergence and rapid spread of gram-negative bacteria resistant to carbapenems among newborns is concerning on a global scale. Nonetheless, the pooled estimate of gram-negative bacteria resistant to carbapenem that cause neonatal sepsis in developing nations remains unknown. Thus, this study aimed to determine the combined prevalence of gram-negative bacteria resistant to carbapenem in African newborns who were suspected of having sepsis.
METHODS: All studies published from January 1, 2010, up to December 30, 2023, from PubMed, Science Direct, Scopus electronic databases, and the Google Scholar search engine were researched. Isolates tested for carbapenem from neonates with sepsis, English language papers conducted in Africa, and cross-sectional and cohort studies papers were included. Using PRISMA guidelines, we systematically reviewed and meta-analyzed studies that assessed the prevalence of carbapenem-resistant gram-negative bacteria. The \"Joanna Briggs Institute\" was used critically to evaluate the quality of the included studies. The data analysis was carried out using STATA™ version 17. Heterogeneity across the studies was evaluated using Q and I 2 tests. The subgroup analysis was done and, funnel plot and Egger\'s regression test were used to detect publication bias. A sensitivity analysis was conducted.
RESULTS: All 36 studies were included in the meta-analysis and systematic review. The pooled prevalence of carbapenem resistance in Africa was 30.34% (95% CI 22.03-38.64%). The pooled estimate of gram-negative bacteria resistant to imipenem, and meropenem was 35.57% (95% CI 0.67-70.54%) and 34.35% (95% CI 20.04% - 48.67%), respectively. A. baumannii and Pseudomonas spp. had pooled prevalence of 45.9% (95% CI 33.1-58.7%) and 43.0% (95% CI 23.0-62.4%), respectively. Similarly, Pseudomonas spp. and A. baumannii also exhibited strong meropenem resistance, with a pooled prevalence of 29.2% (95% CI 4.8-53.5%) and 36.7% (95% CI 20.1-53.3%), respectively. E. coli and K. pneumoniae were the two most common isolates.
CONCLUSIONS: There should be urgent antimicrobial stewardship practices, strengthened surveillance systems and effective treatment for neonates with sepsis. There was remarkable variation in resistance across the continent.

Neonatal sepsis is a common and severe infectious disease with a high mortality rate. Its pathogenesis is complex, lacks specific manifestations, and has a low positive culture rate, making early diagnosis and personalized treatment still a challenge for clinicians. Epidemiological studies on twins have shown that genetic factors are associated with neonatal sepsis. Gene polymorphisms are closely related to susceptibility, disease development, and prognosis. This article provides a review of gene polymorphisms related to neonatal sepsis, including interleukins, tumor necrosis factor, Toll-like receptors, NOD-like receptors, CD14, triggering receptor expressed on myeloid cells-1, mannose-binding lectin, and other immune proteins, aiming to promote precision medicine for this disease.
新生儿败血症是常见的感染性疾病，病情严重，病死率高。其发病机制复杂，缺乏特异性表现，培养阳性率低，早期诊断和个体化治疗仍然是临床医生面临的挑战。对双胞胎的流行病学研究表明，遗传因素与新生儿败血症存在关联。基因多态性与其易感性、病情发展和预后密切相关。该文就新生儿败血症相关的白细胞介素、肿瘤坏死因子、Toll样受体、NOD样受体、CD14、髓系细胞触发受体1、甘露糖结合凝集素和其他免疫蛋白基因多态性进行综述，以期促进该疾病的精准医疗。.

BACKGROUND: Early-onset neonatal sepsis (EONS) significantly impacts neonatal morbidity and mortality, with maternal bacteremia during the peripartum period being a potential risk factor. This study aims to explore the association between peripartum maternal bacteremia and EONS.
METHODS: A retrospective cohort study at the Women\'s Wellness and Research Center in Doha, Qatar (2015-2019) compared women with and without bacteremia, based on blood cultures taken from up to seven days before to 48 h after delivery, examining the association with EONS.
RESULTS: Among the 536 maternal blood cultures analyzed, 102 (19.0%) were positive. The most prevalent organisms were Group B streptococcus (GBS) (39.2%), followed by Escherichia coli (14.7%) and anaerobes (10.8%). Neonates from bacteremic mothers had lower birth weights (2913 ± 86 g vs. 3140 ± 745 g; MD 227.63 g; 95% CI 61.72 - 393.55; p = 0.007), required more resuscitation (27.5% vs. 13.2%; OR 2.48; 95% CI 1.48 - 4.17; p < 0.001), and received antibiotics for ≥ 7 days more frequently (41.2% vs. 16.6%; OR 3.51; 95% CI 2.20 - 5.62; p < 0.001) compared to those from non-bacteremic mothers. Maternal Gram-positive (GP) organisms were more commonly isolated in term gestation (67.9%) compared to Gram-negative (GN) (22.2%) and anaerobic bacteremias (9.9%). During intrapartum, GP bacteremia was predominant (67.1%) vs. GN (21.4%) and Anaerobes (11.4%), with GN bacteremia being more common in postpartum samples. Culture-proven EONS occurred in 0.75% of the cohort, affecting 3.9% of infants from bacteremic mothers vs. none in controls (OR 2.34; 95% CI 1.27 - 4.31; p < 0.001). Culture-negative EONS appeared in 14.7% of infants from bacteremic mothers vs. 7.8% in controls (OR 2.02; 95% CI, 1.05 - 3.88; p = 0.03). Among 40 cases of maternal GBS bacteremia, culture-proven GBS EONS occurred in 3 neonates (7.5%), all from mothers with negative GBS screening, compared to none in the control group. A strong association was found between EONS and maternal bacteremia due to any organism (aOR 2.34; 95% CI, 1.24 - 4.41; p = 0.009), GP bacteremia (aOR 3.66; 95% CI, 1.82 - 7.34; p < 0.001), or GBS (aOR 5.74; 95% CI, 2.57 - 12.81; p < 0.001). Bacteremia due to GN and Anaerobic organisms were not associated with EONS. Chorioamnionitis and antepartum fever were independent predictors for EONS associated with significant bacterial isolates.
CONCLUSIONS: This study underscores the significant impact of maternal GP bacteremia, particularly from GBS, on EONS. The strong association highlights the need for vigilant monitoring and interventions in pregnancies complicated by bacteremia to reduce adverse neonatal outcomes.

Group B Streptococcus (Streptococcus agalactiae; GBS) is a leading cause of neonatal sepsis worldwide. As a pathobiont of the intestinal tract, it is capable of translocating across barriers leading to invasive disease. Neonatal susceptibility to invasive disease stems from immature intestinal barriers. GBS intestinal colonization induces major transcriptomic changes in the intestinal epithelium related to barrier function. Butyrate, a microbial metabolite produced by fermentation of dietary fiber, bolsters intestinal barrier function against enteric pathogens, and these effects can be transferred in utero via the placenta to the developing fetus. Our aim was to determine if butyrate mitigates GBS disruption of intestinal barriers. We used human intestinal epithelial cell (IEC) lines to evaluate the impact of butyrate on GBS-induced cell death and GBS adhesion and invasion. IECs and human fetal tissue-derived enteroids were used to evaluate monolayer permeability. We evaluated the impact of maternal butyrate treatment (mButyrate) using our established mouse model of neonatal GBS intestinal colonization and late-onset sepsis. We found that butyrate reduces GBS-induced cell death, GBS invasion, monolayer permeability, and translocation in vitro. In mice, mButyrate decreases GBS intestinal burden in offspring. Our results demonstrate the importance of bacterial metabolites, such as butyrate, in their potential to bolster epithelial barrier function and mitigate neonatal sepsis risk.IMPORTANCEGroup B Streptococcus (GBS) is a leading cause of neonatal morbidity and mortality. It is a commensal of the intestines that can translocate across barriers leading to sepsis in vulnerable newborns. With the rise in antibiotic-resistant strains and no licensed vaccine, there is an urgent need for preventative strategies. Butyrate, a short-chain fatty acid metabolized in the gut, enhances barrier function against pathogens. Importantly, butyrate is transferred in utero, conferring these benefits to infants. Here, we demonstrate that butyrate reduces GBS colonization and epithelial invasion. These effects were not microbiome-driven, suggesting butyrate directly impacts epithelial barrier function. Our results highlight the potential impact of maternal dietary metabolites, like butyrate, as a strategy to mitigate neonatal sepsis risk.

Neonatal capillary leak syndrome (CLS) is a rare, but life-threatening condition following neonatal sepsis or inflammatory injury. The objective of this study was to describe a standardized treatment approach for CLS that improves mortality and neonatal outcomes. A retrospective cohort study of 10 infants born at 22 to 26 weeks of gestation who developed CLS following a significant inflammatory insult was performed. Time to diagnosis and treatment approaches over 2 epochs were recorded and described. In epoch 2, with increased clinical awareness of CLS and implementation of a standardized treatment approach, there was a non-statistically significant decrease in the time to treatment with a significant decrease in mortality. An early targeted treatment approach for neonatal CLS can decrease mortality rates in this highly morbid condition.

Background: The microbiota in the intestine is made up of trillions of living bacteria that coexist with the host. Administration of antibiotics during neonatal infection causes depletion of gut flora resulting in gut dysbiosis. Over the last few decades, probiotics have been created and promoted as microbiota management agents to enrich gut flora. Probiotics decrease the overgrowth of pathogenic bacteria in the gut of preterm neonates, reducing the frequency of nosocomial infections in the Neonatal Intensive Care Unit (NICUs). Methods: The systematic review will include randomized control trials (RCTs) of premier neonates with sepsis. Studies will be retrieved from global databases like Cochrane CENTRAL, CINAHL Plus via EBSCO host, MEDLINE via PubMed, EMBASE, SCOPUS, Ovid, Web of Science, ProQuest Medical Library, Microsoft academic, and DOAJ by utilizing database-specific keywords. Screening, data extraction, and critical appraisal of included research will be carried out separately by two review writers. Findings will be reported in accordance with the PRISMS-P 2020 guidelines. Conclusions: The findings of this systematic review will help to translate the evidence-based information needed to encourage the implementation of potential research output in the field of neonatal intensive care, guide best clinical practise, assist policy making and implementation to prevent gut dysbiosis in neonates with sepsis by summarising and communicating the evidence on the topic. PROSPERO registration number: This systematic review protocol has been registered in PROSPERO (Prospective Register of Systematic Reviews) on 10 th March 2022. The registration number is CRD42022315980.

BACKGROUND: 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)].
CONCLUSIONS: 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.

This study reports a case of multidrug resistant Candida krusei as the cause of early neonatal sepsis in a term small-for-gestational age neonate weighing 1680 g that successfully responded to voriconazole therapy. Both blood culture and urine culture of the neonate sent on day 4 and day 8 respectively showed Gram positive oval budding yeast cells on Gram staining which was confirmed as C. krusei susceptible only to voriconazole by Vitek 2 Compact (Biomérieux, France) automated system. Voriconazole was given for fourteen days leading to good clinical response with microbiological clearance of fungus from blood and no side-effects.

Sepsis is a common disease with high morbidity and mortality among newborns in intensive care units world-wide. Gram-negative bacillary bacteria are the major source of infection in neonates. Gentamicin is the most widely used aminoglycoside antibiotic in empiric therapy against early-onset sepsis. However, therapy failure may result due to various factors. The purpose of this study was to identify predictors of gentamicin therapy failure in neonates with sepsis. This was a prospective cross-sectional study at the Neonatal Intensive Care Unit at Windhoek Central Hospital over a period of 5 months in 2019. Neonates received intravenous gentamicin 5 mg/kg/24 h in combination with either benzylpenicillin 100 000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Logistic regression modeling was performed to determine the predictors of treatment outcomes. 36% of the 50 neonates were classified as having gentamicin treatment failure. Increasing treatment duration by 1 day resulted in odds of treatment failure increasing from 1.0 to 2.41. Similarly, one unit increase in CRP increases odds of gentamicin treatment failure by 49%. The 1 kg increase in birthweight reduces the log odds of treatment failure by 6.848, resulting in 99.9% decrease in the odds of treatment failure. One unit increase in WBC reduces odds of gentamicin treatment failure by 27%. Estimates of significant predictors of treatment failure were precise, yielding odds ratios that were within 95% confidence interval. This study identified the following as predictors of gentamicin therapy failure in neonates: prolonged duration of treatment, elevated C-reactive protein, low birthweight, and low white blood cell count.

BACKGROUND: Currently, there are hundreds of hematological parameters used for rapid diagnosis of neonatal sepsis, but there is no network meta-analysis to compare the diagnostic efficacy of these parameters.
METHODS: We searched for literature on the diagnostic neonatal sepsis and selected 20 of the most common parameters to compare their diagnostic efficacy. We used Bayesian network meta-analysis, Frequentist network meta-analysis, and individual traditional diagnostic meta-analysis to analyze the data and verify the stability of the results. Based on the above analysis, we ranked the diagnostic efficacy of 20 parameters and searched for the optimal indicator. We also conducted subgroup analysis based on different designs. GRADE was used to evaluate the quality of evidence.
RESULTS: 311 articles were included in the analysis, of which 206 articles were included in the network meta-analysis. Bayesian models fond the top three of the advantage index were P-SEP, SAA, and CD64. In Individual model, P-SEP, SAA, and CD64 had the best sensitivity; ABC, SAA, and P-SEP had the best specificity. Frequentist model showed that CD64, P-SEP, and IL-10 ranked in the top three for sensitivity, while P-SEP, ABC, and I/M in specificity. Overall, P-SEP, SAA, CD64, and PCT have good sensitivity and specificity among all the three methods. The results of subgroup analysis were consistent with the overall analysis. All evidence was mostly of moderate or low quality.
CONCLUSIONS: P-SEP, SAA, CD64, and PCT have good diagnostic efficacy for neonatal sepsis. However, further studies are required to confirm these findings.