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.

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.

Shorter versus longer duration antibiotic regimens for treatment of culture-positive neonatal sepsis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the safety and effectiveness of shorter versus longer duration antibiotic regimens for the treatment of culture-positive neonatal sepsis with or without meningitis.

Antibiotic Stewardship in Chorioamnionitis Exposed Neonates, A Quality Improvement Project.

BACKGROUND: Rates of neonatal early onset sepsis (EOS) in term infants have recently decreased. The 2018 AAP guidelines for the management of infants at risk for early onset sepsis allows for using a multivariate risk assessment to determine need for empiric antibiotics in infants 35 weeks or greater, including those exposed to chorioamnionitis. METHODS: A quality improvement (QI) project was undertaken to implement use of EOS calculator in chorioamnionitis exposed infants with an aim to safely decrease antibiotic exposure. Multiple Plan-Do-Study-Act (PDSA) cycles occurred to implement the change. Data regarding antibiotics, labs, length of stay and safety metrics were collected. RESULTS: Implementing the EOS calculator's use in chorioamnionitis exposed neonates decreased antibiotic exposure from 100% to 75%, and decreased average duration of antibiotics from 68 to 40 hours. Implementation decreased prolonged courses of antibiotics, lumbar punctures, length of stay and laboratory tests. No cases of early culture confirmed EOS were missed, and none occurred in this well appearing population. CONCLUSIONS: Quality improvement initiatives to implement evidence-based tools can safely and appropriately decrease antibiotic exposure in neonates.

Analysis of Differences in Neonatal Sepsis Caused by Streptococcus Agalactiae and Escherichia Coli.

BACKGROUND: Streptococcus agalactiae (GBS) and Escherichia coli (E. coli) are the main pathogenic bacteria in neonatal sepsis. Therefore, the clinical characteristics, nonspecific indicators, and drug susceptibilities of these two bacteria were studied. METHODS: In total, 81 and 80 children with sepsis caused by GBS and E. coli infection, respectively, admitted to the neonatal department of our hospital between May 2012 and July 2023, were selected, and the clinical characteris-tics of the two groups were analyzed. Nonspecific indicators and drug sensitivity test results were analyzed retrospectively. RESULTS: Birth weight, tachypnea, groan, tachycardia or bradycardia, and the incidence of complications, such as pneumonia, respiratory failure, and purulent meningitis, were higher in the GBS group than in the E. coli group. The children were born prematurely, and the mother had a premature rupture of membranes. The incidence of jaundice, abdominal distension, atypical clinical manifestations, and complications of necrotizing enterocolitis was lower than of the E. coli group, and the differences were statistically significant (p < 0.05). The WBC, NE#, NE#/LY#, hs-CRP, and PCT of the GBS group were higher than those of the E. coli group, whereas the MPV, D-D, and FDP levels were lower than those in the E. coli group. The differences were all statistically significant (p < 0.05). The 81-bead GBS had high resistance rates against tetracycline (95%), erythromycin (48.8%), and clindamycin (40%), and no strains resistant to vancomycin, linezolid, penicillin, or ampicillin appeared, whereas 80 strains of E. coli were more resistant to penicillin and third-generation cephalosporins, with the higher resistance rates to ampicillin (68.30%), trimethoprim/sulfamethoxazole (53.6%), and ciprofloxacin (42.90%). Resistance rates to carbapenems and aminoglycosides were extremely low. CONCLUSIONS: Both GBS and E. coli neonatal sepsis have specific clinical characteristics, especially in terms of clinical manifestations, complications, non-specific indicators, and drug resistance. Early identification is important for clinical diagnosis and treatment.

Role of central endpoint adjudication and challenges in trials on neonatal sepsis-a case of ProSPoNS trial.

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on "sepsis," the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the "physician diagnosed sepsis." To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that "physician diagnosed sepsis" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine "physician diagnosed sepsis": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

Risk factors for mortality in culture-negative neonatal sepsis in Malawi: a propensity score-matched analysis.

We conducted a propensity score-matched multivariable regression analysis of 1050 culture-negative neonatal sepsis cases in Malawi, where 160 (15.2%) died. Mortality among neonates with culture-negative sepsis was associated with very low birth weight (adjusted OR (AOR) 12.82, 95% CI 1.23 to 137.49), respiratory distress syndrome (AOR 13.20, 95% CI 2.58 to 83.66), a low Apgar score at 1 min (AOR 3.50, 95% CI 1.21 to 10.72) and at 5 min (AOR 4.77, 95% CI 1.94 to 12.50). Addressing maternal and perinatal factors around health and delivery of care is key to improving outcomes in the context of culture-negative sepsis in neonates from low-income country settings like Malawi.

Exploring factors influencing delayed first antibiotic treatment for suspected early-onset sepsis in preterm newborns: a study before quality improvement initiative.

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) (ß = 0.07, P = 0.013), penicillin skin test (PST) timing (ß = 0.06, P < 0.001) and medical order timing (ß = 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).

Vitamin D Metabolites in Mother-Infant Dyads and Associated Clinical Outcomes in a Population of Nigerian Women.

Low levels of vitamin D in maternal and cord blood have been associated with neonatal sepsis. This study assessed the association of vitamin D metabolites (25(OH)D, 3-epi-25(OH)D3, and 24,25(OH)2D3) levels in maternal and cord blood with newborn sepsis evaluation in Nigerian mother-infant dyads. Maternal and cord blood from 534 mothers and 536 newborns were processed using liquid chromatography-tandem mass spectrometry. Spearman correlation was used to compare continuous variables, Mann-Whitney for dichotomous variables, and Kruskal-Wallis for two or more groups. High cord percent 3-epi-25(OH)D3 levels were positively associated with newborn evaluation for sepsis (p = 0.036), while maternal and cord 25(OH)D and 24,25(OH)2D3 levels were not. Being employed was positively associated with maternal and newborn 3-epi-25(OH)D3 concentrations (p = 0.007 and p = 0.005, respectively). The maternal 3-epi-25(OH)D3 and percent 3-epi-25(OH)D3 were positively associated with vaginal delivery (p = 0.013 and p = 0.012, respectively). Having a weight-for-age Z-score ≤ -2 was positively associated with newborn percent 3-epi-25(OH)D3 levels (p = 0.004), while a weight-for-length Z-score ≤ -3 was positively associated with maternal and newborn percent 3-epi-25(OH)D3 levels (p = 0.044 and p = 0.022, respectively). Our study highlights the need to further investigate the biological role of 3-epi-25(OH)D3 and its clinical significance in fetal growth and newborn outcome.

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.

Quality improvement initiative 'S-A-F-H' to reduce healthcare-associated neonatal sepsis in a tertiary neonatal care unit.

BACKGROUND: Neonatal sepsis is a leading cause of morbidity and mortality among admitted neonates. Healthcare-associated infection (HAI) is a significant contributor in this cohort. LOCAL PROBLEM: In our unit, 16.1% of the admissions developed sepsis during their stay in the unit. METHOD: We formed a team of all stakeholders to address the issue. The problem was analysed using various tools, and the main contributing factor was low compliance with hand hygiene and handling of intravenous lines. INTERVENTIONS: The scrub the hub/aseptic non-touch technique/five moments of hand hygiene/hand hygiene (S-A-F-H) protocol was formulated as a quality improvement initiative, and various interventions were done to ensure compliance with hand hygiene, five moments of hand hygiene, aseptic non-touch technique. The data were collected and analysed regularly with the team members, and actions were planned accordingly. RESULTS: Over a few months, the team could reduce the incidence of HAI by 50%, which has been sustained for over a year. The improvement in compliance with the various aspects of S-A-F-H increased. CONCLUSIONS: Compliance with hand hygiene steps, five moments of hand hygiene and an aseptic non-touch technique using quality improvement methodology led to a reduction in neonatal sepsis incidence in the unit. Regular reinforcement is required to maintain awareness of asepsis practices and implementation in day-to-day care and to bring about behavioural changes.

Challenges and opportunities in neonatal sepsis management: insights from a survey among clinicians in 25 Sub-Saharan African countries.

BACKGROUND: Neonatal sepsis (NS) is a global health issue, particularly in Sub-Saharan Africa, where it accounts for a substantial portion of neonatal morbimortality. This multicountry survey aimed to elucidate current practices, challenges and case definitions in managing NS among clinicians in Sub-Saharan Africa. METHODS: The survey targeted physicians and medical practitioners working in neonatal care who participated in a Self-Administered Web Questionnaire. The main objective was to understand NS and infection case definitions and management from the clinician's point of view and to identify challenges and opportunities in sepsis management. Participants were queried on demographics, definitions and diagnostic criteria, treatment approaches, and infection prevention and control (IPC) measures. A total of 136 participants from 93 healthcare structures responded, providing valuable insights into NS management practices. RESULTS: From May to July 2022 across 21 Sub-Saharan African countries, 136 neonatal clinicians with an average from 93 structures with on average 10-year experience took the survey. NS ranked highest among prevalent neonatal conditions. Diagnostic case definitions between sepsis and infection were attributed to clinical signs, anamnesis, C reactive protein, white blood cll count and blood cultures with no statistically significant differences. Early-onset sepsis was defined within 72 hours by 48%, while late-onset varied. Antibiotics were likely on admission (86.4%) and during the stay (82.2%). Treatment abandonment was reported unlikely. The preferred antibiotic regimen for early-onset sepsis was intravenous amoxicillin (or ampicillin), gentamycin and cefotaxime. Blood culture availability and IPC protocols were reported as limited, particularly concerning patient environment, pharmacy protocols and clean-dirty circuits. CONCLUSIONS: This NS survey emphasises clinicians' challenges due to limited access to diagnostic tools and raises concerns about antimicrobial overexposure. IPC also seem limited, according to participants. Addressing these challenges can enhance diagnostic practices, antibiotic stewardship and infection control in the region.

Machine Learning: A Potential Therapeutic Tool to Facilitate Neonatal Therapeutic Decision Making.

Bacterial infection is one of the major causes of neonatal morbidity and mortality worldwide. Finding rapid and reliable methods for early recognition and diagnosis of bacterial infections and early individualization of antibacterial drug administration are essential to eradicate these infections and prevent serious complications. However, this is often difficult to perform due to non-specific clinical presentations, low accuracy of current diagnostic methods, and limited knowledge of neonatal pharmacokinetics. Although neonatal medicine has been relatively late to embrace the benefits of machine learning (ML), there have been some initial applications of ML for the early prediction of neonatal sepsis and individualization of antibiotics. This article provides a brief introduction to ML and discusses the current state of the art in diagnosing and treating neonatal bacterial infections, gaps, potential uses of ML, and future directions to address the limitations of current studies. Neonatal bacterial infections involve a combination of physiologic development, disease expression, and treatment response outcomes. To address this complex relationship, future models could consider appropriate ML algorithms to capture time series features while integrating influences from the host, microbes, and drugs to optimize antimicrobial drug use in neonates. All models require prospective clinical trials to validate their clinical utility before clinical use.

Evaluating a Modified Use of the Kaiser Permanente Early-onset Sepsis Risk Calculator to Reduce Antibiotic Exposure: a Retrospective Study.

BACKGROUND: Early-onset neonatal sepsis (EONS) remains an important disease entity due to very serious adverse outcomes if left untreated. Lack of diagnostic tools in identifying healthy from diseased neonates, and clinicians' fear of the missing positive-culture sepsis babies, or babies with clinical sepsis have led to overtreating and unnecessary antibiotic exposure. Kaiser Permanente EONS risk calculator is an internally validated tool that can predict EONS. This sepsis risk calculator (SRC) classifies neonates into three subgroups: (1) ill-appearing, (2) equivocal and (3) well-appearing. We propose a modification to this tool that aims to use it solely for well-appearing babies. This modification represents a more conservative approach to decrease antibiotic exposure and offers an alternative for those hesitant to fully implement this tool. METHODS: This is a dual-centre retrospective study where data were extracted from the electronic medical records. Our primary outcome was to validate the modified use of the SRC with a two-by-two table. Specificity, negative predictive value and expected antibiotic reduction were used to evaluate the tool's feasibility. RESULT: Among 770 babies suspected of EONS, the feasibility of the modified use was tested. The expected antibiotic exposure reduction rate on the modification was 40.4% overall. The proposed modification resulted in a specificity and negative predictive value of 99.28% (95% CI: 97.92% to 99.85%) and 99.5% (95% CI: 99% to 99.8%), respectively. CONCLUSION: The modified use of the sepsis risk calculator has shown that it can safely reduce antibiotic exposure in well-appearing babies. The modified use is used as a 'rule out' test that can identify very low risk of EONS babies, and safely minimise antibiotic exposure. Further prospective studies are needed to examine the efficacy of this use, and quality improvement projects are required to evaluate its applicability in different clinical settings.

A meta-analysis of the association between inflammatory cytokine polymorphism and neonatal sepsis.

OBJECTIVE: The purpose of this study is to investigate the relationship between single nucleotide polymorphisms of inflammatory cytokines and neonatal sepsis through meta-analysis. METHODS: We collected research literature on the correlation between inflammatory cytokine polymorphisms and neonatal sepsis published before August 2023 through computer searches of databases such as PubMed, Embase, etc. The Stata 14.0 software was utilized for Meta-analysis. To assess heterogeneity, the chi-squared Q-test and I2 statistics were used. The Egger and Begg tests were conducted to determine the possibility of publication bias. RESULTS: After reviewing 1129 articles, 29 relevant articles involving 3348 cases and 5183 controls were included in the study. The meta-analysis conducted on IL-1ßrs1143643 polymorphism revealed significant findings: the T allele genotype has a lower risk of neonatal sepsis(P = 0.000, OR = 0.224, 95% CI: 0.168-0.299), while the TC and TT genotypes showed an increased risk(TC: P = 0.000,OR = 4.251, 95% CI: 2.226-8.119; TT: P = 0.019,OR = 2.020, 95% CI: 1.122-3.639). Similarly, newborns with the IL-6-174 CC genotype had a significantly higher risk of sepsis(P = 0.000,OR = 1.591, 95% CI: 1.154-2.194), while those with the IL-8-rs4073 TT (P = 0.003,OR = 0.467, 95% CI: 0.280-0.777)and TT + AA(P = 0.003,OR = 0.497, 95% CI: 0.315-0.785) genotypes had a significantly lower risk of sepsis. For the IL-10-1082 gene, newborns with the AA genotype(P = 0.002,OR = 1.702, 95% CI: 1.218-2.377), as well as those with the AA + GA genotype(P = 0.016,OR = 1.731, 95% CI: 1.108-2.705), had a significantly higher risk of sepsis. Lastly, newborns carrying the TNF-α-308 A allele (P = 0.016,OR = 1.257, 95% CI: 1.044-1.513)or the AA genotype(P = 0.009,OR = 1.913, 95% CI: 1.179-3.10) have a significantly increased risk of sepsis. Notwithstanding, additional studies must be included for validation. Applying these cytokines in clinical practice and integrating them into auxiliary examinations facilitates the early detection of susceptible populations for neonatal sepsis, thereby providing a new diagnostic and therapeutic approach for neonatal sepsis.

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.

Neonatal bacterial sepsis.

Neonatal sepsis remains one of the key challenges of neonatal medicine, and together with preterm birth, causes almost 50% of all deaths globally for children younger than 5 years. Compared with advances achieved for other serious neonatal and early childhood conditions globally, progress in reducing neonatal sepsis has been much slower, especially in low-resource settings that have the highest burden of neonatal sepsis morbidity and mortality. By contrast to sepsis in older patients, there is no universally accepted neonatal sepsis definition. This poses substantial challenges in clinical practice, research, and health-care management, and has direct practical implications, such as diagnostic inconsistency, heterogeneous data collection and surveillance, and inappropriate treatment, health-resource allocation, and education. As the clinical manifestation of neonatal sepsis is frequently non-specific and the current diagnostic standard blood culture has performance limitations, new improved diagnostic techniques are required to guide appropriate and warranted antimicrobial treatment. Although antimicrobial therapy and supportive care continue as principal components of neonatal sepsis therapy, refining basic neonatal care to prevent sepsis through education and quality improvement initiatives remains paramount.

Optimal use of ß-lactams in neonates: machine learning-based clinical decision support system.

BACKGROUND: Accurate prediction of the optimal dose for ß-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections. METHODS: Five ß-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses. FINDINGS: For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses. INTERPRETATION: An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal ß-lactam antibiotic doses. FUNDING: This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.

Association of low vitamin D level and full-term early-onset neonatal sepsis; a case-control study.

BACKGROUND: Sepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country. METHODS: This case-control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture. RESULTS: Forty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml). CONCLUSION: In the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis).

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

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