Neonatal Sepsis Research Articles

Value of Combination of Heart Rate Observation (HeRO) Score and The Newborn Early Warning (NEW) System in Early Diagnosis of Sepsis in Preterm Infants

Abstract Background Although all newborns are at an increased risk of developing sepsis, this is particularly true for premature infants because of their immune systems haven’t fully matured. Early detection of sepsis, prior to overt clinical deterioration, would allow earlier institution of antibiotics and supportive therapies will result in better outcomes. Aim of the Work The aim of this study was to determine the effectiveness of combination of HeRO score and NEW system in early detection of neonatal sepsis in preterm infants by using HeRO score and NEW chart combined together. Methods The study included 170 preterm infants at Ain Shams Children Hospital, Cairo, Egypt: Prospective observational study. All studied neonates were subjected to NEW and HeRO scores which displayed a number or score, which represented the risk that a patient would experience clinical deterioration. Confirmation of neonatal sepsis done by withdrawal of C-reactive protein (CRP) and Blood culture. NEW system and HeRO scores followed throughout their hospital stay. The NEW system score chart divided into 3 colours (white, Amber and red). These colours used for identifying the risk for the patient. A HeRO score of 1 is “normal” for healthy preterm infants, and a score of 5 indicates a five-fold increased risk that the patient will be diagnosed with sepsis within the next 24 hours up to 5 days. Results The total number of our studied neonates were divided according to the sepsis or not into 80 neonates were sepsis free, 69 neonates who had initial sepsis and 21 who developed sepsis and NEW and HeRO scores showed statistically higher significance in patients with initial sepsis and developed sepsis than non-septic patients. NEW and HeRO score were significantly higher in septic patients than non- septic patients as cut of value of NEW and HeRO scores was >1 and >0 respectively. Conclusion The combination of HeRO score and NEW system can be used for early detection of neonatal sepsis in preterm infants.

Familial Hemophagocytic Lymphohistiocytosis Screening in Neonatal Sepsis.

Neonatal sepsis and familial hemophagocytic lymphohistiocytosis (fHLH) have similar clinical and laboratory symptoms and the possibility of overlooking fHLH diagnosis is high in newborns with sepsis. History of consanguineous marriage and/or sibling death, hepatomegaly/splenomegaly, and hyperferritinemia (>500ng/mL) are likely to support fHLH in newborns with sepsis. Therefore, in newborns with sepsis in whom at least 2 of these 3 criteria were detected, genetic variants was investigated for the definitive diagnosed of fHLH. According to the results of genetic examination, we investigated whether these criteria supporting fHLH could be used as a screening test in fHLH. fHLH-associated genetic variants were investigated in 22 patients diagnosed with neonatal sepsis who fulfilled at least 2 of the following criteria (1) history of consanguineous marriage and/or sibling death, (2) hepatomegaly/splenomegaly, and (3) hyperferritinemia (>500ng/mL). Heterozygous variants were determined in 6 patients (27.2%): 3 STXBP2 , 1 STX11 , 1 UNC13D , and 1 PRF1 . Polymorphisms associated with the clinical symptoms and signs of HLH were determined in 5 patients (22.7%): 4 UNC13D , 1 PRF1 . Two patients were in the heterozygous variants and polymorphism associated with the clinical symptoms and signs of HLH groups. In 12 patients, benign polymorphisms were detected in STXBP2 and UNC13D genes. No change in fHLH associated genes were found in 1 patient. Some variants and/or polymorphisms identified in our patients have been previously reported in patients with HLH. Therefore, we recommend further investigation of fHLH in patients with neonatal sepsis who fulfill at least 2 of the above 3 criteria.

Antibiotic Management for Early-Onset Sepsis in Neonates With Gestational Ages of ≥ 34 Weeks: The Kaiser Sepsis Calculator Versus the 2010 CDC Guidelines.

The traditional approach to neonatal early-onset sepsis (NEOS) management, involving maternal risk factors and nonspecific neonatal symptoms, usually leads to unnecessary antibiotic use. This study addresses these concerns by evaluating the Kaiser sepsis calculator (KSC) in guiding antibiotic therapy for NEOS, especially in high-incidence facilities (over 4/1,000 live births), by comparing it against the 2010 Centers for Disease Control and Prevention (CDC) guidelines for neonates ≥34 weeks with suspected sepsis, thereby emphasizing its implications for personalized patient care. This is a prospective observational study. All neonates of 34 gestational weeks or more, presenting with either maternal risk factors or sepsis symptoms within 12 hours of birth, were included in the study. The analysis focused on antibiotic recommendations by the 2010 CDC guidelines versus those by the KSC at presumed (0.5/1,000) and actual (16/1,000) sepsis incidence rates. NEOS was identified in 14 cases (14.1%). Compared to the KSC, at an incidence rate of 16 per 1,000, the KSCresulted in a significant 32.3% reduction in antibiotic treatment (74 cases (74.7%) vs. 42 cases (42.4%), respectively; p < 0.001). The calculator advised immediate antibiotic utilization for 13 out of 14 (92.9%) diagnosed cases, suggesting further evaluation for the remaining cases. When a presumed incidence of 0.5/1,000 was applied, the KSC indicated antibiotics less frequently than when using the actual rate of 16/1,000 (p<0.001) with two missed NEOS cases. Using the KSC led to a decrease of 32 cases (32.3%)in unnecessary antibiotic prescriptions compared to adherence to 2010 CDC guidelines. However, setting a presumed incidence below the actual rate risked missing NEOS. The calculator was effective when actual local incidence rates were used, ensuring no missed cases needing antibiotics.

Epidemiology of Neonatal Sepsis in Haiti

Introduction: Neonatal sepsis (NS) is a global public health concern, particularly affecting developing countries. Challenges in diagnostics, more specifically, culture and antimicrobial susceptibility testing hinder effective management of the disease. Objective: This study aims to evaluate the burden, describe the management, and assess the evolution of NS in a hospitalized pediatric population in Haiti. Methods: A retrospective cohort study from January 2013 to December 2018 at La Paix University Hospital was conducted. All-cause hospitalizations and deaths were extracted from hospital’s Neonatology Unit records and were used to derive data regarding hospitalization and death among patients under 28 days with NS. Clinical and laboratory data were extracted from the patients’ medical records. Results: Out of 2,424 post-childbirth hospitalizations, 1,590 involved sepsis. The percentage of hospitalization due to NS was approximately 69% and the percentage of deaths, 65%. The mean age of patients with NS was 3.75 days (0 - 22 days), with a slight male predominance (55%, p &lt; 0.001). Peaks were observed from May to August (p = 0.02). Early NS cases (NS in patients aged less than 7 days) were most prevalent (86%, p &lt; 0.001). Specimen culture and antimicrobial susceptibility testing was less frequent (7%) than complete blood count usage (65%). Findings regarding blood count included leukopenia (3%), thrombocytopenia (30%). A positive CRP and acute renal failure were noted in 76% and 21.7% of cases, respectively. The average hospital stay was 7.3 days. With regards to treatment, 73% of patients received a 2-drug antimicrobial therapy (ampicillin-gentamycin) and 22% received a 3-drug antimicrobial therapy (ampicillin-gentamycin-cefotaxime). Of all newborns hospitalized for NS, 49% received empirical antibiotic therapy within 3 hours of admission. Conclusions: This research highlights NS as a public health emergency in Haiti. The study advocates for improved access to culture and antibiotic susceptibility testing and emphasizes the impact of timely antibiotic administration. The findings of this study serve as a baseline for informing policymakers and medical practitioners dedicated to improving existing conditions of neonates in Haiti. Suggested targeted interventions include preventive measures during prenatal visits, strengthening laboratory capacities, improving infection prevention and control measures, and developing antimicrobial stewardship programs.

Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants

Retinopathy of prematurity (ROP) is a major morbidity of preterm infants causing visual impairment, including blindness, for which timely treatment is vital and prevention is key. Increasing evidence suggests that exposure to neonatal sepsis contributes to ROP development. To investigate the association between neonatal sepsis and ROP in 2 large-scale cohorts of preterm infants born at less than 29 weeks' gestation. This retrospective cohort study was conducted using data from the German Neonatal Network (GNN) and Norwegian Neonatal Network (NNN). The GNN involves 68 and the NNN includes 21 level III neonatal intensive care units. Participants were infants born at a gestation of 22 weeks and 0 days to 28 weeks and 6 days and enrolled in the GNN between January 1, 2009, and December 31, 2022, and NNN between January 1, 2009, and December 31, 2018. Data were analyzed from February through September 2023. Single or multiple episodes of culture-proven sepsis. Any ROP and treatment-warranted ROP. Among 12 794 infants in the GNN (6043 female [47.2%] and 6751 male [52.8%]; mean [SD] gestational age, 26.4 [1.5] weeks) and 1844 infants in the NNN (866 female [47.0%] and 978 male [53.0%]; mean [SD] gestational age, 25.6 [1.5] weeks), the mean (SD) birth weight was 848 (229) g and 807 (215) g, respectively. Any ROP was present in 6370 infants (49.8%) in GNN and 620 infants (33.6%) in NNN, and treatment-warranted ROP was present in 840 infants (6.6%) in GNN and 140 infants (7.6%) in NNN. In both cohorts, there were increasing rates of treatment-warranted ROP with each sepsis episode (no sepsis: 572 of 10 658 infants [5.4%] in GNN and 85 of 1492 infants (5.7%) in NNN; 1 episode: 190 of 1738 infants in GNN [10.9%] and 29 of 293 infants [9.9%] in NNN; 2 episodes: 53 of 314 infants in GNN [16.9%] and 13 of 49 infants [26.5%] in NNN; 3 episodes: 25 of 84 infants [29.8%] in GNN and 3 of 10 infants [30.0%] in NNN). After adjusting for multiple confounders in the GNN dataset, the number of sepsis episodes was associated with ROP and treatment-warranted ROP compared with 0 episodes (1 episode: adjusted odds ratio [aOR], 1.44 [95% CI, 1.27-1.63]; P < .001 and OR, 1.60 [95% CI, 1.31-1.96]; P < .001, respectively; 2 episodes: OR, 1.81 [95% CI, 1.35-2.42]; P < .001 and OR, 2.38 [95% CI, 1.68-3.37]; P < .001, respectively; 3 episodes: OR, 4.39 [95% CI, 2.19-8.78]; P < .001 and OR, 3.88 [95% CI, 2.29-6.55]; P < .001, respectively). These associations were confirmed for any ROP by propensity score matching (for example, the aOR with propensity score matching was 1.76 [95% CI, 1.54-2.02]; P < .001 for 1 episode vs 0 episodes and 1.58 [95% CI, 1.12-2.22]; P = .007 for 3 episodes vs 0 or 1 episode). In the NNN dataset, surgical NEC was associated with treatment-warranted ROP (multivariable analysis: aOR, 3.37 [95% CI, 1.78-6.37]; P < .001). This study found that in the large-scale GNN cohort, recurrent culture-proven sepsis was associated with ROP and treatment-warranted ROP in infants born at less than 29 weeks.

Evaluation of Procalcitonin and Presepsin in prediction for early onset neonatal sepsis.

Objective: To determine the presepsin and procalcitonin significance in cord blood and compare with lactate and C-Reactive protein for early prediction of neonatal sepsis. Study Design: Case Control Study. Setting: Military Hospital Rawalpindi. Period: Sep 2018 to July 2019. Methods: Mothers, having deliveries with early or prolonged rupture of membrane, preterm, dai handled, meconium and failure of induction have been included. Out of 60 neonates, nineteen were cases with a clearly documented suspicion of sepsis and confirmed by neonatologists, remaining were control. Mean and Standard Deviation were calculated. The difference in all biochemical markers levels among case and control groups were assessed by independent t-test. Sensitivity, specificity, accuracy, and predictive value of both markers were calculated by medcalc diagnostic calculator. Regression analysis to access the strength. Receiver Operating Characteristics curve for most accurate cut off values and Area Under the Curve was calculated. Results: Independent sample t test revealed the strong association of procalcitonin and presepsin with neonatal sepsis. Presepsin has higher positive predictive value 83.33% and negative predictive value 90.48% with 88.33% accuracy while procalcitonin has positive predictive value 62.50%, negative predictive value 88.89% and accuracy 78.33%. Stepwise regression analysis showed better in combination than single in predication of neonatal sepsis. The cutoff value for procalcitonin was 0.4ng/ml (AUC of 84.5%.) and for presepsin was 305pg/ml (AUC of 86.5%). Conclusion: In comparison to lactate and CRP, a prediction model that incorporates two biochemical indicators, procalcitonin and presepsin, can reduce infant mortality and morbidity by spotting neonatal sepsis early.

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

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. 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. 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. 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.

Trends of Early Onset Group B Streptococcus infections and Observed Racial and Geographic Disparities Associated with GBS Infections in Tennessee, 2005-2021

Background: Group B Streptococcus (GBS) is one of the most common causes of bacterial sepsis in newborns. In 2002, the Center for Disease Control and Prevention (CDC) recommended universal screening of all pregnant women for GBS colonization and administering intrapartum prophylaxis to colonized pregnant women to prevent GBS infection in newborns. To identify racial disparities in GBS infections in Tennessee, we compared the incidence of early-onset GBS infection among Black and White infants from 2005-2021. Methods: GBS infections identified from normally sterile sites are reportable in Tennessee. We analyzed GBS data reported to surveillance systems from 2005 to 2021. We linked the surveillance data with the population data to calculate incidence rates. We excluded cases with unknown race status (9%) and other races (0.2%) as we do not have denominator data to calculate the incidence rate. Database linkage and data analyses were performed in SAS V.9.4. Results: A total of 399 early-onset GBS cases were reported from 2005–2021; 150 (37.59%) were Black, 212 (53.13%) were White, and 36 (9.02%) were of unknown race, and one (0.20%) reported as Other for race. While the incidence rates of early-onset GBS for all races declined from 0.23 per 1000 live births in 2005 to 0.18 per 1000 live births in 2021, Blacks experienced the largest decline in incidence from 0.6 per 1000 live births in 2005 to 0.37 in 2021. Among Whites, there was a slight decline in 2021 (0.13/1000 live births) compared to the rate in 2005 (0.21/1000 live births). The mean incidence rate of early onset GBS among Blacks (0.52 per 1000 live births) is significantly higher than the mean rates among Whites (0.20 per 1000 live births) (p value &lt; 0 .001) from 2005 to 2021. Shelby County, one of the 95 counties in Tennessee, is predominantly Black (54.6%) and reported 27.8% of all early-onset GBS. Conclusion: There was a significant decline in early-onset GBS infections among Blacks and some reductions among Whites, indicating the effectiveness of the prevention strategies. However, Blacks have significantly higher rates than their White counterparts. In addition, 27.8% of the cases are reported from one county, signaling geographic disparities as well. Further investigation is warranted to identify risk factors and causes of observed racial and geographic disparities to help reduce the infection rate among vulnerable populations and high-risk geographic areas.

Study of Incidence, Risk Factors, and Outcome of Acute Kidney Injury in Neonatal Intensive Care Unit at Tertiary Care Center

Acute Kidney Injury (AKI) remains a notable cause of morbidity and mortality in neonates and the costs of care for patients with AKI are also very expensive, particularly in developing countries like Nepal. The global burden of AKI is quite high specially in lo w-middle-income countries and has very limited data on the incidence of AKI worldwide and the data vary generally in different studies This is a hospital based retrospective cross-sectional study of neonates admitted at Nepal Medical College and Teaching Hospital (NMCTH) from January 2022 till January 2023. Among 318 admitted newborns, incidence of AKI was found to be 18 (5.7%) with male to female ratio of 3:1 in AKI group. The mean length of hospital stay was 13 days, which was longer in AKI group in comparison to non AKI group which was 6.3 days. The rate of neonatal AKI varied within the gestational age cohorts: lower the gestational age more chance of AKI as 28 -32 weeks (n=3/17, 17.6 %) had more incidence of AKI in compare to older gestational age as 32–36 weeks (n=3/50, 6%), and ≥37 weeks (n=12/250, 4.8 %). Meconium stained liquor and pregnancy induced hypertension were the maternal risk factors found to be associated with the development of AKI. Respiratory distress syndrome (RDS) was the commonest cause of neonatal AKI (44.40%), followed by neonatal sepsis (38.90%) and fluid overload (38.90%). In term of outcomes all the cases were discharged from non AKI group while among AKI group mortality was 4/15 (22.2%). Stage 3 AKI had poor prognosis with 100% mortality. Use of nephrotoxic drugs was the main cause of morbidity and mortality of AKI in both discharged and expired group. This showed that this vulnerable population need to be taken care early with effective management and awareness should be developed for the better understanding of the epidemiology of AKI in neonates as there is high risk of developing chronic kidney disease (CKD).

Evaluation of cardiac output in neonatal sepsis

Background: Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in the 1st month of life imposing significant cardiovascular compromise which poses a huge burden of morbidity. The essential objective of functional neonatal echocardiography is to recognize features of cardiovascular compromise earlier and help in timely institution of management. This study provides an overview regarding the variability of cardiac output (CO) in neonates with culture-positive sepsis. Aims and Objectives: The aims and objectives of the study are to assess the variability of CO in term neonates with Gram-positive sepsis and Gram-negative sepsis. Materials and Methods: The observational cross-sectional study was conducted in the Department of Paediatrics for 18 months in a tertiary care center. 2D echocardiography was performed on all the neonates who came positive for sepsis screen within the first 2 days of institution of antibiotics. CO was calculated from the echocardiographic finding of Aortic Root Diameter (d), Velocity Time Integral, and Heart Rate recorded at the same time. Normal range of left ventricular output has been defined as 150–300 mL/kg/min each. Results: In Gram-negative group, the mean CO (Mean±SD) of patients was 386.4545±34.2284 mL/kg/min while in Gram-positive group, the mean CO (Mean±SD) of patients was 345.1532±37.6044 mL/kg/min and the variation stands significant at P&lt;0.0001. Conclusion: This research confers about hyperdynamic circulatory status of neonatal sepsis as reflected by increased CO beyond the normal limit in septic neonates. On comparison, a strikingly higher CO was observed in Gram-negative sepsis group than Gram-positive group.

Early Diagnosis of Neonatal Sepsis Using Hematological Profiles

ABSTRACT Preterm and extremely low-birth-weight newborns are at a higher risk for early-onset neonatal sepsis (NN-SP). This condition is often linked to intrapartum fever, PROM, and sepsis occurring within the first day of life. The causal pathogen can be acquired through intrauterine transmission or from the mother’s flora. Therefore, our study aimed to evaluate PC and PI in cases involving NN-SP. Therefore, we can conclude that analyzing the PC and its indices can improve the prognosis of sepsis in NN. Studying NN using this method is a cost-effective approach that helps prevent mortality and morbidity. Early identification of newborn sepsis can help reduce the associated medical tests and medical bills. Clinical correlation with specific indicators and tools is a method for achieving this.

Temporal decreases in pathogen colonization and infection among hospitalized neonates following routine skin antisepsis with chlorhexidine gluconate: Botswana 2022 – 2023

Background: Multidrug-resistant Gram-negative bacteria are a major cause of sepsis among hospitalized neonates globally. Aqueous chlorhexidine gluconate (CHG) skin antisepsis has been shown to be safe for use in infants; however, its sustained effectiveness in preventing Gram-negative pathogen colonization, bloodstream infection (BSI), and mortality is unclear. Methods: We conducted a period prevalence survey, with 26 sampling events over 12 months (18 October 2022 – 31 October 2023) at a 33-bed neonatal unit in a tertiary public hospital in Botswana where ESBL-producing Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii are leading causes of BSI. Perirectal and periumbilical skin swabs were collected every two weeks from all inpatients. Swabs were inoculated onto chromogenic media selective and differential for extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) and Acinetobacter spp. (CHROMagar™ ESBL, Acinetobacter). Colonization status was determined based on culture growth and colony morphology. Contemporaneous data on all-cause mortality and BSI were abstracted from routine surveillance records. Pre- and post-CHG prevalences were compared using a simple Chi-square test. During the surveillance period, an outbreak of K. pneumoniae linked to contaminated multi-use vials was detected, thus BSIs and deaths during the outbreak period (2 February–6 April, 2023) were excluded. In February 2023, the hospital infection prevention and control (IPC) team introduced twice-weekly whole-body cleansing with commercially available 2% aqueous CHG, performed by caregivers and healthcare workers on neonates &gt;24 hours old and weighing ≥1 kg until discharge. Results: There were significant decreases in ESBL-E and Acinetobacter skin and perirectal colonization following the CHG intervention (Table 1; Figure 1). After the CHG intervention, the incidence of Acinetobacter BSIs declined significantly and there was a trend toward a decline in other BSIs and mortality. No adverse events associated with CHG were reported. Conclusions: Twice-weekly CHG application was temporally associated with significant reductions in neonatal ESBL-E and Actinetobacter skin and perirectal colonization and Acinetobacter BSI. This analysis was limited by a short pre-intervention surveillance period and thus may have been influenced by confounders such as seasonality, and intensified IPC efforts following the outbreak. Analysis of the routine CHG use in other settings and over longer surveillance periods are needed to better understand its effectiveness as an IPC strategy in settings where neonatal sepsis incidence is high. Table 1. Colonization prevalence, BSI incidence, and mortality surrounding introduction of CHG skin cleansing in a neonatal unit, 18 October 2022 – 31 October 2023.

External Evaluation of Population Pharmacokinetic Models of Piperacillin in Preterm and Term Patients from Neonatal Intensive Care.

Piperacillin/tazobactam is extensively used off-label to treat late-onset neonatal sepsis, but safety and pharmacokinetic data in this population are limited. Additionally, the organic immaturity of the newborns contributes to a high piperacillin pharmacokinetic variability. This affects the clinical efficacy of the antibiotic treatment and increases the probability of developing drug resistance. This study aimed to evaluate the predictive performance of reported piperacillin population pharmacokinetic models for their application in a model-informed precision dosing strategy in preterm and term Mexican neonatal intensive care patients. Published population pharmacokinetic models for piperacillin which included neonates in their study population were identified. From the reference models, structured models, population pharmacokinetic parameters, and interindividual and residual variability data were extracted to be replicated in pharmacokinetic software (NONMEM® version 7.4). For the clinical study, a sampling schedule was designed, and 2-3 blood samples of 250 µL were taken from neonates who met the inclusion criteria. Piperacillin plasma concentrations were determined by liquid chromatography/tandem mass spectrometry. The clinical treatment data were collected, and piperacillin plasma concentrations were estimated using reference pharmacokinetic models for an a priori or Bayesian approach. Statistical methods were used in terms of bias and precision to evaluate the differences between observed and estimated neonatal piperacillin plasma concentrations with the different approaches and to identify the pharmacokinetic model that best fits the neonatal data. A total of 70 plasma samples were collected from 25 neonatal patients, of which 15 were preterm neonates. The overall median value (range) postnatal age, gestational age, body weight, and serum creatinine at the sampling collecting day were 12 (3-26) days, 34.2 (26-41.1) weeks, 1.78 (0.08-3.90) Kg, 0.47 (0.20-0.90) mg/dL, respectively. Three population pharmacokinetic models for piperacillin in infants up to 2months were identified, and their predictive performance in neonatal data was evaluated. No pharmacokinetic model was suitable for our population using an a priori approach. The model published by Cohen-Wolkowiez et al. in 2014 with a Bayesian approach showed the best performance of the pharmacokinetic models evaluated in our neonatal data. The procedure requires two blood samples (predose and postdose), and, when applied, it predicted 66.6% of the observations with a relative median absolute predicted error of less than 30%. The population pharmacokinetic model developed by Cohen-Wolkowiez et al. in 2014 demonstrated superior performance in predicting the plasma concentration of piperacillin in preterm and term Mexican neonatal intensive care patients. The Bayesian approach, including two different piperacillin plasma concentrations, was clinically acceptable regarding bias and precision. Its application for model-informed precision dosing can be an option to optimize the piperacillin dosage in our population.

Cluster of Differentiation 163 Level in the Blood as a Predictor of Early and Late Onset Neonatal Sepsis

Cluster of Differentiation 163 Level in the Blood as a Predictor of Early and Late Onset Neonatal Sepsis

Glomerular Filtration Rate in Sick Neonates: A Focus on Cystatin C

Background: The use of creatinine as an endogenous marker of estimated glomerular filtration rate (eGFR) is well-established in clinical practice, despite its limitations. As a step toward limiting this drawback, cystatin C and various biomarkers came into use in determining renal function. In sick neonates, various pathologies may impair renal function thus, underscoring the need for accurate estimation of glomerular filtration rate (GFR). Aims and Objectives: This study aimed at evaluating the use of cystatin C in estimating the GFR of sick neonates in comparison to creatinine. Materials and Methods: A hospital-based descriptive study was conducted at a tertiary center in North Central, Nigeria, for 4 months. One hundred and seventy-three sick neonates admitted into the special care baby unit were recruited. Blood was sampled at admission for determination of serum creatinine and cystatin C levels, while a repeat sample for creatinine was taken 48 hours after. GFR was estimated using the Schwartz formula for creatinine and the Zappitelli equation for cystatin C and compared with an inulin reference. Results: The median (interquartile range [IQR]) eGFR derived from cystatin C was 48.8 (21.0) mL/min/1.73 m2, it was higher than the median creatinine-derived GFR at admission and was of statistical significance. It is also approximated closer to the inulin reference. The median (IQR) eGFR derived from creatinine at admission was 21.2 (21.4) mL/min/1.73 m2. Creatinine-derived eGFR was significantly lower in babies with asphyxia and neonatal sepsis compared to those who did not have these diagnoses. Cystatin C-derived eGFR showed no variation between the various diagnoses. Conclusion: In conclusion, cystatin C is a useful and unbiased determinant of eGFR in sick neonates as compared to creatinine.

Early-onset neonatal sepsis diagnosis – still a challenge after 30 years - Part 1

Despite all the advances in diagnosis and treatment, early-onset neonatal sepsis remains a serious and potentially life-threatening condition, with increased morbidity and mortality. The authors review the persistent controversies and challenges surrounding the definitions of neonatal sepsis, neonatal early- and late-onset sepsis, clinical signs and risk factors, and different approaches for identifying neonates at risk for early-onset sepsis. The impact of neonatal early-onset sepsis on short- and long-term outcomes is also resumed.

Hypoglycemia in a term newborn small for gestational age with early onset sepsis - literature review and case report

Neonatal hypoglycemia presents significant challenges in the management of small for gestational age (SGA) infants with early onset sepsis. This literature review and case report examine the clinical implications and therapeutic strategies in such cases. The study underscores the importance of timely recognition and intervention to mitigate the risks associated with hypoglycemia and sepsis in term newborns, emphasizing early glucose management and appropriate antibiotic therapy for optimal outcomes.

Association of red cell distribution width (RDW) with positive blood culture of neonatal sepsis in Khartoum state, Sudan

BackgroundThe red cell distribution width (RDW) was higher among neonates with early onset neonatal sepsis. The study aimed to determine the red cell distribution width (RDW) with positive blood culture of early onset neonatal sepsis. This was a descriptive laboratory-based study, conducted during the period from January to September 2023, done on a total of 244 blood sample containers, tested for Complete Blood Count (CBC) tests and blood culture for who were diagnosed as early onset neonatal sepsis.ResultsIn this study (244) neonates were diagnosed as blood culture proven neonatal sepsis, The study showed that the cultured organism was isolated as following: 95 were Staphylococcus aureus, 70 were Candida Spp, 28 were Pseudomonas ssp, then 27 were Klebsiella ssp, 16 were Escherichia coli, after that 6 were Enterococcus feacalis and finally 2 were Listeria monocytogenes, and the RDW in this study was significantly higher in neonatal sepsis with average range (20 ± 2.5%).ConclusionsThe study concluded that RDW at levels more than or equal to 17% was the most sensitive hematological marker to predict mortality of neonatal sepsis.

Ligilactobacillus salivarius V4II-90 eradicates Group B Streptococcus colonisation during pregnancy: a randomised, double-blind, placebo-controlled trial.

Group B Streptococcus (GBS) is the leading cause of bacterial neonatal sepsis. This study aimed to confirm the effect of Ligilactobacillus salivarius V4II-90 on GBS colonisation during pregnancy. A randomised, multicentre, double-blind, placebo-controlled, parallel-group study was conducted in seven hospitals in Madrid, Spain. The sample was broken down into two groups with 20 participants each (n= 40) in order to show reduced GBS colonisation frequency in the probiotic versus the placebo group. Pregnant participants positive for vaginal-rectal colonisation before or during the 13th week of gestation were randomly assigned to either the placebo or the probiotic group. The probiotic, L. salivarius V4II-90 at 1× 109cfu/day was administered for 12 weeks, starting at week 21-23 of gestation. The primary outcome was the percentage of participants with vaginal and/or rectal GBS colonisation at the end of the intervention period (35 weeks of gestation). Secondary outcomes were changes in the microbial composition of vaginal and rectal exudates; premature delivery; premature rupture of membranes; intrapartum antibiotics; new-borns with early or late-onset GBS sepsis; adverse events (AEs); and GBS test results performed at the hospital at week 35 of gestation. Of the 481 participants included, 44 were vaginal-rectal colonised with GBS and randomised. 43 completed the study (20 in the probiotic group and 23 in the placebo group). After intervention, GBS was eradicated in six participants (27%) from the placebo group and in twelve participants (63%) from the probiotic group ( P = 0.030). None of the 185 AEs reported were identified as possibly, probably, or definitely related to the investigational product. In conclusion, oral administration of L. salivarius V4II-90 is a safe and successful strategy to significantly decrease the rates of GBS colonisation at the end of pregnancy and, therefore, to reduce the exposure of subjects and their infants to intrapartum antibiotic prophylaxis. Trial registered at ClinicalTrials.gov: number NCT03669094.

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

BackgroundEarly-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes.PurposeThe 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.MethodsIn 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.ResultsThe mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (β = 0.07, P = 0.013), penicillin skin test (PST) timing (β = 0.06, P < 0.001) and medical order timing (β = 0.04, P = 0.017) were significantly associated with the initial timing of antibiotic administration.ConclusionsThere 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).