Loop-mediated isothermal amplification (LAMP) assay for early on-site detection of Group B Streptococcus infection in neonatal sepsis blood sample.

BACKGROUND: Neonatal sepsis, often attributed to Group B Streptococcus (GBS) infection, poses a critical health risk to infants, demanding rapid and accurate diagnostic approaches. Existing diagnostic approaches are dependent on traditional culture methods, a process that requires substantial time and has the potential to delay crucial therapeutic assessments. METHODS: This study introduces an innovative Loop-Mediated Isothermal Amplification (LAMP) assay for the early on-site detection of GBS infection from neonatal sepsis blood samples. To develop a LAMP assay, the primers are designed for the selective targeting of a highly conserved segment within the cfb gene encoding the CAMP factor in Streptococcus agalactiae ensuring high specificity. RESULTS: Rigorous optimization of reaction conditions, including temperature and incubation time, enhances the efficiency of the LAMP assay, enabling rapid and reliable GBS detection within a short timeframe. The diagnostic efficacy of the LAMP assay was evaluated using spiked blood samples by eliminating the DNA extraction step. The simplified colorimetric LAMP assay has the capability to detect S. agalactiae in a neonatal blood sample containing 2 CFU/mL during sepsis. Additionally, the LAMP assay effectively detected S. agalactiae in both the standard and spiked blood samples, with no detectable interference with blood. CONCLUSION: This optimised LAMP assay emerges as a promising tool for early GBS detection, offering a rapid and accurate on-site solution that has the potential to inform timely interventions and improve outcomes in neonatal sepsis cases.

Time to Positivity of Blood Culture as a Predictor of Causative Pathogens and Survival in Neonatal Sepsis: A Retrospective Cohort Study from Indonesia.

Objectives: In the blood culture procedure for neonatal sepsis, time to positivity (TTP) reflects the pathogenic bacterial load and the time required for empirical antibiotic regimen administration prior to definitive treatment. This study aims to identify the differences in TTP among causative pathogens and its predictive value for the overall survival of neonates with sepsis at a tertiary healthcare center in Indonesia. Methods: A retrospective cohort study was conducted from January 2020 to August 2022 at Dr. Soetomo General Hospital, Surabaya, Indonesia. Neonates with blood culture-proven neonatal sepsis were included in the analysis. TTP was defined as the time between the acceptance of a blood culture specimen from the neonatal intensive care unit and reports of positive culture growth by the laboratory. Results: Across 125 cases, the median TTP was 58.1 hours (IQR = 24.48). Blood cultures were positive within 48 hours for 41.6% of cases, 72 hours for 86.4%, and 96 hours for 98.4%. A significantly shorter TTP was exhibited by the three major gram-negative organisms (Klebsiella pneumoniae,Acinetobacter baumannii,Enterobacter cloacae) compared to coagulase-negative Staphylococci. The neonatal sepsis mortality rate was 49.6% during the study period. In the Cox multivariate regression model, a shorter TTP was an independently predicted mortality in the entire cohort (hazard ratio (HR) = 0.985, 95% CI: 0.973-0.998) and the gram-negative sepsis cohort group (HR = 0.983, 95% CI: 0.968-0.999). Conclusions: TTP predicts different causative pathogens and the overall survival of neonatal sepsis cases at a tertiary healthcare facility in Indonesia.

An Observational Study on C-Reactive Protein to Platelet Ratio in Neonatal Sepsis.

BACKGROUND: Neonatal sepsis is a serious medical condition affecting many individuals in the developing world. C-reactive protein (CRP) level in serum and platelet counts have been reported to have role in diagnosis of neonatal sepsis. OBJECTIVE: To evaluate the CRP to Platelet ratio (CPR) in relation to time and blood culture reports in neonatal sepsis patients from a tertiary care centre in the Marathwada region of Maharashtra. METHODS: The present observational study was conducted at the level III Neonatal Intensive Care Unit of a tertiary care centre in Aurangabad city of Marathwada region in Maharashtra from September 2022 to July 2023. The study included 120 neonates (delivered after completion of 28-42 weeks of gestation) with clinical/culture-positive sepsis. The newborns of seropositive mothers, neonates delivered in other hospitals, babies with congenital dysmorphic features, and babies requiring surgical procedures were excluded from the study. Blood samples for complete blood count (CBC) and CRP were collected on days 1, 3 and 5. Blood cultures were sent on day 1 of illness. Repeated measures ANOVA was used to compare the parameters of CPR, CRP, and platelet count in blood culture-positive and blood culture-negative neonatal sepsis patients on days 1, 3 and 5. RESULTS: Blood culture was positive in 37 (30.8%) cases. A repeated measures ANOVA showed a significant overall difference in the CPR across days 1, 3, and 5 (p = 0.006). The CPR was significantly higher in culture-positive neonates compared to culture-negative neonates (p = 0.042). CONCLUSION: Higher CPR in blood culture-positive neonates compared to blood culture-negative neonates supports the role of CPR in the diagnosis and management of neonatal sepsis.

Factors associated with neonatal sepsis among neonates admitted in Kibungo Referral Hospital, Rwanda.

More than one million neonatal deaths occur every year worldwide, of which 99% take place in low-income countries. In Rwanda, nearly 71% of neonatal deaths are preventable and among these, 10% are due to neonatal sepsis. Nevertheless, limited information exists on neonatal sepsis and its associated factors in Rwanda. The objectives of the study were to find prevalence and factors associated with neonatal sepsis among neonates admitted in Kibungo Referral Hospital, Ngoma District, Rwanda. We used a retrospective cross-sectional study design reviewing a subset of neonatal, maternal and laboratory records from Kibungo Hospital in 2017. Data were reviewed and collected from March to May, 2018. Logistic regression and odds ratios were calculated to identify the factors associated with neonatal sepsis at 95% CI, p < 0.05. Of the 972 total neonates' medical records from 2017, we randomly selected 422 of which 12.8% (n = 54) had neonatal sepsis. When blood cultures were positive, 62% grew Klebsiella pneumoniae. Among neonates with sepsis, 38 (70%) recovered while 16 (30%) died. Neonatal sepsis was strongly associated with neonatal age less than or equal to three days (aOR: 2.769, 95% CI 1.312-5.843; p = 0.008); and gestational age less than 37 weeks (aOR: 4.149; CI 1.1878-9.167; p ≤ 0.001). Increased use of blood cultures including sensitivity testing, routine surface cultures of the neonatology and maternity wards facilities, and systematic ward cleaning are all important approaches to prevent and treat neonatal infections in additional to regular neonatal sepsis evaluations.

Characteristics of Neonatal Sepsis and Predictive Values of Polyfunctional Assessment of Umbilical Cord Neutrophils Based on Single Cell Proteomic Secretion.

The early diagnosis of neonatal sepsis is crucial as it remains a prevalent cause of neonatal mortality. In this study, we conducted an analysis on the clinical data and detection indicators of 22 cases with sepsis and 62 cases without sepsis among neonates. Our findings indicate that the clinical signs observed in neonates with sepsis lack specificity. In addition, the commonly used clinical inflammatory indicators (such as leukocyte count, neutrophil-to-lymphocyte ratio [NLR], C-reactive protein [CRP], procalcitonin) exhibit limited sensitivity and specificity. Furthermore, the current clinical measures lack the assessment of inflammatory factors. Therefore, in order to enhance the accuracy of early sepsis diagnosis in neonates, we have employed a novel microfluidic-based single-cell technology platform for the analysis of 32 cytokines secreted by neutrophils at the individual cell level under various toxin stimulation conditions. We have further investigated and compared the disparities in single-cell protein secretomics between umbilical cord blood neutrophils and healthy adult peripheral neutrophils within an in vitro sepsis model. Our findings indicate that in a resting state UCB neutrophils exhibited lower polyfunctionality compared with healthy adult blood neutrophils, and notable variations in cytokine secretion profiles were detected between the two groups. However, the polyfunctionality of UCB neutrophils significantly increased and surpassed that of healthy adult neutrophils when exposed to alpha-hemolysin or lipopolysaccharide. UCB neutrophils secreted a wide range of chemokines and inflammatory factors, among which GM-CSF and IL-18 were the most significant. Furthermore, we initially categorized the functional subgroups of neutrophils by considering the secretion of five primary cytokines by neutrophils (GM-CSF, IL-18, IL-8, MIP-1ß, and MIF). The current study, for the first time, examined in detail the heterogeneity of protein secretion and the functional diversity of UCB neutrophils stimulated by different antigens. Moreover, new insight into neonatal sepsis, early diagnosis, and wider clinical applications of UCB neutrophils are provided by these data.

PeRinatal, neOnatal, and Maternal OuTcomEs with azithromycin prophylaxis in pregnancy and labour (PROMOTE-PROPHYLAXIS): systematic review and meta-analysis.

Background: Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; however, the recent evidence did not show any benefit to neonatal survival. There is conflicting evidence over the role of azithromycin prophylaxis in antenatal and intrapartum periods. We explored whether azithromycin prophylaxis in pregnant women improves maternal and neonatal outcomes. Methods: For this systematic review and meta-analysis registered on PROSPERO [CRD42023411093], we searched seven databases (PubMed, Scopus, Embase, Cochrane Library, EBSCOHost, ProQuest, and Web of Science) and clinical trial registries until 04/23/2024, for RCTs evaluating antenatal/intrapartum azithromycin prophylaxis against placebo/routine care in pregnant women. The primary outcome was neonatal mortality. Intrapartum and antenatal administration were assessed separately. We used random-effects meta-analysis. The risk of bias was assessed using the Cochrane RoB 2 tool. The GRADE approach was used to evaluate the certainty of the evidence. Findings: Screening 2161 records retrieved 20 RCTs (56,381 participants). Intrapartum azithromycin may make little or no difference to neonatal mortality [5 RCTs, 44,436 participants; Risk Ratio (RR): 1.02, 95% CI 0.86-1.20, I 2  = 0%, very low certainty], and maternal mortality [3 RCTs, 44,131 participants, RR: 1.26, 0.65-2.42, I 2  = 0%, low certainty]. Similarly, antenatal azithromycin may have little or no effect on neonatal mortality [3 RCTs; 5304 participants; RR: 0.74, 0.35-1.56, I 2  = 43%, very-low certainty] and maternal mortality [3 RCTs; 8167 participants RR: 1.62, 0.67-3.91, I 2  = 0%, low certainty]. There is no data on long-term adverse outcomes and antimicrobial resistance. Interpretation: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality. Funding: None.

Antibiotics and beyond: Unraveling the dynamics of bronchopulmonary dysplasia in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care. Prenatal inflammation and neonatal sepsis contribute to the multifactorial nature of BPD. A potential association between empirical antibiotic therapy and BPD risk has been proposed due to microbiota dysbiosis in very low birth weight premature infants. METHODS: A single centered retrospective cohort study of preterm infants (24-32 weeks gestation) from 2014 to 2021. The study compared groups that received empirical antibiotics in the first days of life and those that did not receive any antibiotic in the first days of life. The primary outcomes studied were BPD, death, and the combined outcome of BPD/death. Statistical analysis employed t-tests, Mann-Whitney U, Chi-square, and logistic regression. RESULTS: Of 454 preterm infants, 61.5% received antibiotics. This group had lower gestational age, birth weight, and Apgar scores. Antibiotic use was associated with higher incidence of BPD (35.5% vs. 10.3%), death (21.5% vs. 8.6%), and combined outcomes (54.5% vs. 18.3%). In multivariate analysis, antibiotic use independently associated with BPD (OR 2.58, p < 0.001) and combined outcome BPD/death (OR 2.06, p < 0.02). Antenatal corticosteroids provided protection against BPD, but not mortality. CONCLUSION: This study suggests an association between early empirical antibiotic use and BPD in preterm infants, emphasizing the need for judicious antibiotic practices in neonatal care.

Trends in C-Reactive Protein Use in Early-onset Sepsis Evaluations and Associated Antibiotic Use.

OBJECTIVE: To determine the prevalence of C-reactive protein (CRP) use in early-onset sepsis (EOS) evaluations in neonatal intensive care units (NICUs) across the US over time and to determine the association between CRP use and antibiotic use. STUDY DESIGN: A retrospective cohort study of NICUs contributing data to Premier Healthcare Database from 2009 through 2021. EOS evaluation was defined as a blood culture charge ≤ 3 days after birth. CRP use for each NICU was calculated as the proportion of infants with a CRP test obtained ≤ 3 days after birth among those undergoing an EOS evaluation and categorized as, low (<25%); medium-low (25 to < 50%), medium-high (50 to < 75%), and high (≥75%). Outcomes included antibiotic use and mortality ≤ 7 days after birth. RESULTS: Among 572 NICUs, CRP use varied widely and was associated with time. The proportion of NICUs with high CRP use decreased from 2009 to 2021 (24.7% vs 17.4%, P < .001), and those with low CRP use increased (47.9% vs 64.8%, P < .001). Compared with low-use NICUs, high-use NICUs more frequently continued antibiotics > 3 days (10% vs 25%, P < .001). This association persisted in multivariable-adjusted regression analyses (adjusted risk ratio 1.95, 95%CI 1.54, 2.48). Risk of mortality was not different in high-use NICUs (adjusted risk difference -0.02%, 95%CI -0.04%, 0.0008%). CONCLUSIONS: CRP use in EOS evaluations varied widely across NICUs. High CRP use was associated with prolonged antibiotic therapy but not mortality ≤ 7 days after birth. Reducing routine CRP use in EOS evaluations may be a target for neonatal antibiotic stewardship efforts.

Impacts of COVID-19 pandemic on culture-proven sepsis in neonates.

Objective: To assess the effects of COVID-19 pandemic on the epidemiology of neonatal sepsis and the antibiotic resistance profiles of pathogens involved. Methods: This retrospective cohort study analyzed infants diagnosed with culture-proven sepsis at the neonatal department of a tertiary children's hospital in East China from January 2016 to December 2022. We compared the clinical and microbiological characteristics of neonatal sepsis cases between the pre-pandemic Phase I (2016-2019) and during the COVID-19 pandemic Phase II (2020-2022). Results: A total of 507 infants with 525 sepsis episodes were included, with 343 episodes in Phase I and 182 in Phase II. The incidence of early-onset sepsis (EOS) was significantly lower during Phase II (p < 0.05). Infants in Phase II had lower gestational ages and birth weights compared to Phase I. Clinical signs such as mottled skin, severe anemia, thrombocytopenia were more prevalent in Phase II, alongside a higher incidence of complications. Notably, necrotizing enterocolitis (NEC) (p < 0.05) and meningitis (p < 0.1) occurred more frequently during Phase II. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the predominant pathogens isolated from infants of death and cases with complications. A significant decrease in the proportion of K. pneumoniae was observed in Phase II, alongside increased antibiotic resistance in both E. coli and K. pneumoniae. The period of the COVID-19 pandemic (Phase II) was identified as an independent risk factor for complications in infants with neonatal sepsis. Conclusion: COVID-19 pandemic response measures correlated with a decrease in EOS and an increase in neonatal sepsis complications and antibiotic resistance.

Outcomes of interventions in neonatal sepsis: A systematic review of qualitative research.

BACKGROUND: While a systematic review exists detailing neonatal sepsis outcomes from clinical trials, there remains an absence of a qualitative systematic review capturing the perspectives of key stakeholders. OBJECTIVES: Our aim is to identify outcomes from qualitative research on any intervention to prevent or improve the outcomes of neonatal sepsis that are important to parents, other family members, healthcare providers, policymakers, and researchers as a part of the development of a core outcome set (COS) for neonatal sepsis. SEARCH STRATEGY: A literature search was carried out using MEDLINE, EMBASE, CINAHL, and PsycInfo databases. SELECTION CRITERIA: Publications describing qualitative data relating to neonatal sepsis outcomes were included. DATA COLLECTION AND ANALYSIS: Drawing on the concepts of thematic synthesis, texts related to outcomes were coded and grouped. These outcomes were then mapped to the domain headings of an existing model. MAIN RESULTS: Out of 6777 records screened, six studies were included. Overall, 19 outcomes were extracted from the included studies. The most frequently reported outcomes were those in the domains related to parents, healthcare workers and individual organ systemas such as gastrointestinal system. The remaining outcomes were classified under the headings of general outcomes, miscellaneous outcomes, survival, and infection. CONCLUSIONS: The outcomes identified in this review are different from those reported in neonatal sepsis clinical trials, thus highlighting the importance of incorporating qualitative studies into COS development to encapsulate all relevant stakeholders' perspectives.

Frozen Section of Placental Membranes and Umbilical Cord: A Valid Diagnostic Tool for Early-Onset Neonatal Sepsis Management.

Early-onset neonatal sepsis (EONS), a serious infection in newborns within 3 days, is challenging to diagnose. The current methods often lack accuracy, leading to unnecessary antibiotics or delayed treatment. This study investigates the role of the frozen section examination of placental membranes and umbilical cord (FSMU) to improve EONS diagnosis in the daily lab practice. This retrospective study reviewed data from 59 neonates with EONS risk factors who underwent FSMU according to our institutional protocol. Concordance between the FSMU and the Final Pathological Report (FPR) was assessed. The FSMU demonstrated a high concordance (Kappa = 0.88) for funisitis diagnosis, with excellent accuracy (98.3%). A moderate concordance was observed for chorioamnionitis stage and grade. The FSMU shows promise as a rapid and accurate tool for diagnosing EONS, particularly for funisitis. This study suggests that the FSMU could be a valuable tool for EONS diagnosis, enabling a more judicious antibiotic use and potentially improving outcomes for newborns.

Whole Genome Sequencing of Invasive Neonatal Escherichia coli from Uppsala County, Sweden.

BACKGROUND: This study sought to investigate associations between a virulence factors and phylogeny in all neonatal E. coli bloodstream infections from patients admitted to the neonatal intensive care unit at Uppsala University Hospital between 2005 to 2020. METHODS: A total of 37 E. coli isolates from 32 neonates were whole genome sequenced and analysed for virulence factors related to extraintestinal E. coli, patient-related data were collected retrospectively in the medical records. RESULTS: E. coli isolates that belong to phylogroup B2 were associated with mortality (OR 26, p < 0.001), extreme prematurity with delivery before gestational week 28 (OR 9, p < 0.05) and shock (OR 9, p < 0.05) compared with isolates of non-B2 group. Female neonates were more often infected by isolates of phylogroup B2 E. coli compared with male neonates (OR 7, p = 0.05). The identification of the genotoxin determinant clb coding for colibactin exhibited strong associations with mortality (OR 67, p < 0.005), gestational age (OR 18, p < 0.005), and shock (OR 26, p < 0.005). DISCUSSION: The study highlighted the correlation between neonatal E. coli bacteraemia caused by phylogroup B2 and the role of colibactin. Moreover, it emphasised sex-based differences in bloodstream infections among the bacterial population of E. coli.

The diagnostic performance of mean neutrophil volume in neonatal sepsis: A systematic review and meta-analysis.

BACKGROUND: There is a need for reliable diagnostic tests for early identification of sepsis to prevent neonatal mortality and antibiotic misuse. During sepsis, many immature neutrophils came into the bloodstream, altering the mean neutrophil volume (MNV) shown in the previous studies. OBJECTIVES: To summarize the diagnostic performance of mean neutrophil volume (MNV) in neonatal sepsis from the published literature. METHOD: Databases such as PubMed, Scopus, and Web of Science were searched from January 1990 to April 2023 for studies reporting MNV as a diagnostic test in neonatal sepsis. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve of MNV were estimated with reference blood culture-positive sepsis and clinical sepsis for meta-analysis. RESULT: The diagnostic performance of MNV was analyzed in 1685 neonates, including 829 septic and 856 non-septic neonates, from six prospective studies. The pooled sensitivity and specificity of MNV were 0.87 and 0.75, respectively, for neonatal sepsis; the DOR was 20.01 (95% CI: 5.90-67.82); and the AUC of the SROC for MNV was 0.81 (95% CI: 0.69-0.88). Higgins I2 was 92.1% (95% CI: 85.5%-95.7%). The diagnostic performance of MNV was better during sub-group analysis of studies reporting culture-positive sepsis (DOR 85.61). CONCLUSION: The diagnostic performance of MNV is moderate for neonatal sepsis. As the evidence originated from a small number of studies with marked heterogeneity, further large-scale diagnostic accuracy studies are recommended to resolve heterogeneity in the future.

Myocardial performance imaging for the early identification of cardiac dysfunction in neonates with sepsis.

PURPOSE: The assessment of cardiac performance in septic new-borns is crucial for detecting hemodynamic instability and predicting outcome. The aim of the study is to assess myocardial performance in neonates with sepsis for the early identification of cardiac dysfunction. PATIENTS AND METHODS: A case control study was carried out from September 2022 to May 2023 at the Neonatal Intensive care unit, Kasturba Medical College, Manipal. A total of 68 neonates were included in the study, with 33 females and 35 males. The study population was further subdivided into 3 groups namely preterm septic neonates (n = 21), term septic neonates (n = 10) and non-septic healthy controls (n = 37). The cardiac structure and function were assessed using conventional method, Tissue Doppler imaging (Sm) and speckle tracking echocardiography (GLS). The study was approved by the Institutional Ethics Committee at Kasturba Medical College, Manipal (approval number IEC: 90/2022). The CTRI registration number for the study is CTRI/2022/09/045437 and was approved on September 12, 2022. Prior to the neonate's enrolment, informed consent was obtained from their mothers or legal guardians. RESULTS: Out of the total 68 neonates, 31 were cases and 37 were controls which included 33 females and 35 males. LV systolic function was not statistically significant between cases and controls. E/A ratio of the mitral valve was significantly lower in septic newborns than in healthy neonates. (1.01 ± 0.35 vs 1.18 ± 0.31, p < 0.05) preterm neonates showed significantly lower Lateral E' and RV E' velocities than term neonates. TAPSE was significantly lower in septic preterm neonates. (8.61 ± 1.28 vs. 10.7 ± 2.11, p < 0.05) No significant difference was noted in the Myocardial Performance Index between septic neonates and healthy neonates. LV Global Longitudinal Strain was slightly lower in preterm septic neonates than in term neonates with sepsis. CONCLUSION: Septic newborns are associated with LV diastolic dysfunction, RV systolic dysfunction and substantially higher pulmonary systolic pressures.

[Advances in clinical management of neonatal sepsis]. / 新生儿败血症的临床管理进展.

Neonatal sepsis, as a significant cause of various complications and adverse outcomes in neonates, remains a serious health burden both domestically and internationally. Strategies such as antibiotic prophylaxis during delivery, the utilization of early-onset sepsis risk calculators, and quality improvement initiatives in neonatal wards are beneficial in alleviating the disease burden of neonatal sepsis. This paper provides a review of the epidemiology, risk factors, and recent advances in clinical management of neonatal sepsis.

Factors Associated with Prolonged Antibiotic Therapy in Neonates with Suspected Early-Onset Sepsis.

Early-onset sepsis (EOS) is a rare but profoundly serious bacterial infection. Neonates at risk of EOS are often treated with antibiotics. The start of empiric antibiotic therapy can successfully be reduced by the implementation of the EOS calculator. However, once started, antibiotic therapy is often continued despite a negative blood culture. To decrease the burden of antibiotic therapy, it is necessary to know whether the clinician's reasons are based on objective factors. Therefore, we performed a retrospective single-centre cohort study to identify the factors associated with prolongation of antibiotic therapy in neonates with suspected EOS but a negative blood culture. Maternal, clinical, and laboratory data of neonates with a gestational age of ≥32 weeks, admitted between January 2019 and June 2021, were collected. Among neonates with a negative blood culture, we compared neonates with prolonged (≥3 days) to neonates with discontinued (<3 days) antibiotic therapy. The clinician's reported reasons for prolonging therapy were explored. Blood cultures were positive in 4/146 (2.7%), negative in 131/146 (89.7%), and not obtained in 11/146 (7.5%) of the neonates. The incidence of EOS was 0.7 per 1000 neonates. Of the 131 neonates with a negative blood culture, 47 neonates (35.9%) received prolonged antibiotic therapy. In the prolonged group, the mean gestational age was higher (38.9 versus 36.8 weeks), and spontaneous preterm birth was less prevalent (21.3% versus 53.6%). Prolonged treatment was associated with late onset of respiratory distress, respiratory rate, hypoxia, apnoea and bradycardia, pale appearance, behavioural change, and elevated CRP levels. The most reported reasons were clinical appearance (38.3%), elevated CRP levels (36.2%), and skin colour (10.6%). Prolonging empiric antibiotic therapy despite a negative blood culture is common in suspected EOS. Clinical signs associated with prolongation are uncommon and the reported reasons for prolongation contain subjective assessments and arbitrary interpretations that are not supported by the guideline recommendations as arguments for prolonged therapy.

Diagnostic capacity of miRNAs in neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis is the third leading cause of mortality during the neonatal period, with manifestations atypical and obscure. But the gold standard-blood culture test, requiring 3-5 days, makes it difficult to unveil the final pathogen and leads to the increasing ratio of false-negative results. The empirical method is consulting traditional biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count. However, they are not specific for neonate in diagnostic capacity, especially for infants within three days after delivery, so more novel biomarkers are urgently needed to assist diagnosing neonatal sepsis. microRNAs (miRNAs) have been widely studied in recent years for their diagnostic and prognostic values in different diseases and we conducted a meta-analysis of miRNAs on the topic that whether they are potentially novel biomarkers in early detection of neonatal sepsis. OBJECTIVES: The purpose of the study was to assess whether circulating miRNAs could be used as potential biomarkers for neonatal sepsis, including early and late-onset neonatal sepsis, then calculate their overall accuracy (OA) via meta-analysis. METHODS: PubMed, Cochrane Library, Embase, Web of Science, Scopus, and Ovid databases were retrieved; data cutoff for this analysis was 15 January 2023. Methodological quality assessment of included studies was performed through the Quality in Prognostic Studies tool. Corresponding 95% confidence interval (95%CI) was calculated to present miRNAs' diagnostic value including the pooled sensitivity (Sen), specificity (Spe), positive or negative likelihood ratios (PLR or NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). Differences in OA between the septic group and non-septic group were compared using Chi-square test. RESULTS: After identification, 16 records out of 11 selected articles were eligible for systematic review of miRNAs and four records for PCT; the case group for miRNAs included 945 neonatal sepsis cases; contrast group included 190 respiratory tract infections or pneumonia cases, 60 systemic inflammatory response syndrome (SIRS) cases and 559 healthy neonates. The pooled Sen, Spe, and DOR of miRNAs were 0.87 (95%CI 0.81-0.91), 0.79 (95%CI 0.71-0.85), and 24 (95%CI 12-50), respectively. The pooled Sen, Spe, and DOR of PCT were 0.92 (95%CI 0.83-0.96), 0.64 (95%CI 0.56-0.70), and 20 (95%CI, 7-56), respectively. The OA value of miRNAs was 80.38% and that of PCT was 77.36%, which were not statistically significant difference (p = .13) after the Chi-square test. In addition, no significant publication bias was indicated (p = .92). CONCLUSIONS: Circulating miRNA levels could be applied as diagnostic biomarkers in neonatal sepsis.

The neonatal gut microbiome and global health.

The role of gut microbiome in health, a century-old concept, has been on the center stage of medical research recently. While different body sites, disease conditions, and populations have been targeted, neonatal and early infancy appear to be the most suitable period for such interventions. It is intriguing to note that, unlike traditional use in diarrhea and maintenance of gastrointestinal health, microbiome-mediating therapies have now addressed the most serious medical conditions in young infants such as necrotizing enterocolitis and neonatal sepsis. Unfortunately, almost all new endeavors in this space have been carried out in the Western world leaving behind millions of neonates that can benefit from such manipulations while serving as a large resource for further learning. In this review, an attempt has been made to quantify the global burden of neonatal morbidity and mortality, examples presented on interventions that have failed as a result of drawing from studies conducted in the West, and a case made for manipulating the neonatal gut microbiome to address the biggest killers in early life. A brief comparative analysis has been made to demonstrate the differences in the gut microbiota of North and South and a large clinical trial of synbiotics conducted by our group in a South Asian setting has been presented. Although challenging, the value of conducting such global health research is introduced with an intent to invite medical scientists to engage in well-planned, scientifically robust research endeavors. This can bring about innovation while saving and serving the most vulnerable citizens now and protecting them from the negative health consequences in the later part of their lives, ultimately shaping a resilient and equitable world as pledged by 193 United Nations member countries in 2015.

Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.