Antibiotic use in infants at risk of early-onset sepsis: results from a unicentric retrospective cohort study.

BACKGROUND: Antibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit. METHODS: Retrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy. RESULTS: We included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period. CONCLUSIONS: The use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.

Albumin and C-reactive protein as diagnostic markers for neonatal sepsis: a retrospective study.

OBJECTIVE: To assess the applicability of albumin (ALB) and C-reactive protein (CRP) concentrations in the diagnosis of sepsis in neonates on the day of admission, and to help with early identification and intervention in the development of sepsis. METHODS: This retrospective study included all neonates who were admitted to the neonatal intensive care unit from January 2020 to June 2023. We studied 160 full-term neonates, including 80 with sepsis and 80 healthy controls. A multivariate analysis was conducted to evaluate the associations between ALB, CRP, and sepsis. RESULTS: CRP concentrations were significantly higher in neonates with sepsis than in controls (26.5 ± 8.6 vs. 3.6 ± 1.2 ng/L). At a cut-off point of 10.8 ng/L, CRP showed a sensitivity of 74.3% and a specificity of 80%. Moreover, ALB concentrations were significantly lower in neonates with sepsis than in controls (25.4 ± 2.5 g/L vs. 29.2 ± 2.6 g/L). At a cut-off point of 26.8, ALB showed a sensitivity of 75.6% and a specificity of 84.2%. CONCLUSIONS: Our findings suggest that ALB and CRP concentrations on the first day of admission are different between neonates who do and those who do not develop sepsis. Higher CRP concentrations and lower ALB concentrations may indicate an increased risk of sepsis.

Stenotrophomonas maltophilia neonatal sepsis: a case report.

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacteria known for causing opportunistic and nosocomial infections in humans. S. maltophilia is an emerging pathogen of concern due to it's increasing prevalence, diverse disease spectrum, intrinsic multi-drug resistance and high mortality rates in immunocompromised individuals. S. maltophilia is a rare cause of neonatal sepsis associated with significant morbidity and mortality. The bacterium's multi-drug resistance poses a considerable challenge for treatment, with various mechanisms contributing to its resistance. CASE PRESENTATION: We report a case involving a 40-h-old male African neonate who exhibited symptoms of neonatal sepsis. The blood culture revealed Stenotrophomonas maltophilia, which was sensitive to ciprofloxacin and gentamicin but resistant to other antibiotics. Lumbar puncture for CSF could not be done because the father declined. We treated the newborn with the empirical first-line antibiotics as per the national guideline intravenous ampicillin and gentamicin for six days, and the child recovered fully with a repeated negative blood culture. CONCLUSIONS: This report describes a neonatal sepsis case caused by S. maltophilia, a multi-drug resistant bacteria and a rare cause of neonatal sepsis. We report that early detection of the bacterial and antimicrobial management based on local antibiogram data may be essential for successful patient's management.

The footprint of SARS-COV-2 infection in neonatal late sepsis.

BACKGROUND: Predicting and finding the viral agents responsible for neonatal late-sepsis has always been challenging. METHOD: In this cross-sectional study, which has been done from September 2020 to December 2022, 145 hospitalized neonates suspected to late-onset sepsis alongside routine sepsis workup, were also evaluated for severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) infection, by nasopharyngeal real-time polymerase chain reaction (RT-PCR) or serological tests. RESULT: 145 neonates including 81 girls and 64 boys with a mean age of 12.3 ± 5.9 days and an average hospitalization stay of 23.1 ± 15.4 days were enrolled in the study. While 76.6% of them had negative bacterial culture, 63 patients (43.4%) showed evidence of SARS-COV-2 infection in RT-PCR or serology tests. None of the underlying factors including gender, age, and laboratory investigation had a significant relationship with SARS-COV-2 infection. Similarly, the outcomes of death and length of hospitalization were not different between the two groups with positive and negative SARS-COV-2 RT-PCR (P < 0.05). There was only a significant relationship between radiological changes including reticulonodular pattern, consolidation, pleural effusion, and different types of infiltrations and SARS-COV2 infection. CONCLUSION: Considering the widespread of coronavirus disease 2019 (COVID-19) in newborns, it seems logical to investigate the SARS-COV-2 infection in late-sepsis.

Development of risk prediction nomogram for neonatal sepsis in Group B Streptococcus-colonized mothers: a retrospective study.

Neonatal clinical sepsis is recognized as a significant health problem, This study sought to identify a predictive model of risk factors for clinical neonatal sepsis. A retrospective study was conducted from 1 October 2018 to 31 March 2023 in a large tertiary hospital in China. Neonates were divided into patients and controls based on the occurrence of neonatal sepsis. A multivariable model was used to determine risk factors and construct models.The utilization and assessment of model presentation were conducted using Norman charts and web calculators, with a focus on model differentiation, calibration, and clinical applicability (DCA). Furthermore, the hospital's data from 1 April 2023 to 1 January 2024 was utilized for internal validation. In the modelling dataset, a total of 339 pairs of mothers and their newborns were included in the study and divided into two groups: patients (n = 84, 24.78%) and controls (n = 255, 75.22%). Logistic regression analysis was performed to examine the relationship between various factors and outcome. The results showed that maternal age < 26 years (odds ratio [OR] = 2.16, 95% confidence interval [CI] 1.06-4.42, p = 0.034), maternal gestational diabetes (OR = 2.17, 95% CI 1.11-4.27, p = 0.024), forceps assisted delivery (OR = 3.76, 95% CI 1.72-5.21, p = 0.032), umbilical cord winding (OR = 1.75, 95% CI 1.32-2.67, p = 0.041) and male neonatal sex (OR = 1.59, 95% CI 1.00-2.62, p = 0.050) were identified as independent factors influencing the outcome of neonatal clinical sepsis. A main effects model was developed incorporating these five significant factors, resulting in an area under the curve (AUC) value of 0.713 (95% CI 0.635-0.773) for predicting the occurrence of neonatal clinical sepsis. In the internal validation cohort, the AUC value of the model was 0.711, with a 95% CI of 0.592-0.808. A main effects model incorporating the five significant factors was constructed to help healthcare professionals make informed decisions and improve clinical outcomes.

Late onset neonatal sepsis: Can plasma gelsolin be a promising diagnostic marker?

Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63 ±â€…20.64 vs 451.83 ±â€…209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.

Early procalcitonin assays may reduce antibiotic exposure in premature newborn infants.

AIM: The diagnosis of early-onset neonatal sepsis (EOS) remains difficult. The main aim was to study the effect of a new algorithm for EOS, which includes the level of procalcitonin in umbilical cord blood, on the exposure to antibiotic therapy of premature newborn infants. METHODS: This was a monocentric, observational and retrospective study with before-and-after design. The duration and dose of antibiotic therapy provided as well as the morbidity and mortality were compared in two groups, one included 01 May 2015-30 November 2015 when procalcitonin was not used, and one after the change 01 November 2016-30 May 2017 when procalcitonin was used in a hospital setting in Nice, France. RESULTS: Sixty newborn infants were included in the before group and 54 in the after group. Antibiotic therapy was stopped after 24 h for 18 newborn infants in the after group and four in the before group, and after 48 h for 26 newborn infants in the after group and 10 in the before group. CONCLUSION: The implementation of a new decision-making algorithm including early procalcitonin assay of premature newborn infants significantly reduced exposure to antibiotics without modifying mortality or morbidity.

Application of Advanced Molecular Methods to Study Early-Onset Neonatal Sepsis.

Early-onset sepsis (EOS) is a global health issue, considered one of the primary causes of neonatal mortality. Diagnosis of EOS is challenging because its clinical signs are nonspecific, and blood culture, which is the current gold-standard diagnostic tool, has low sensitivity. Commonly used biomarkers for sepsis diagnosis, including C-reactive protein, procalcitonin, and interleukin-6, lack specificity for infection. Due to the disadvantages of blood culture and other common biomarkers, ongoing efforts are directed towards identifying innovative molecular approaches to diagnose neonates at risk of sepsis. This review aims to gather knowledge and recent research on these emerging molecular methods. PCR-based techniques and unrestricted techniques based on 16S rRNA sequencing and 16S-23S rRNA gene interspace region sequencing offer several advantages. Despite their potential, these approaches are not able to replace blood cultures due to several limitations; however, they may prove valuable as complementary tests in neonatal sepsis diagnosis. Several microRNAs have been evaluated and have been proposed as diagnostic biomarkers in EOS. T2 magnetic resonance and bioinformatic analysis have proposed potential biomarkers of neonatal sepsis, though further studies are essential to validate these findings.

Early detection of late-onset neonatal sepsis from noninvasive biosignals using deep learning: A multicenter prospective development and validation study.

BACKGROUND: Neonatal sepsis is responsible for significant morbidity and mortality worldwide. Its accurate and timely diagnosis is hindered by vague symptoms and the urgent necessity for early antibiotic intervention. The gold standard for diagnosing the condition is the identification of a pathogenic organism from normally sterile sites via laboratory testing. However, this method is resource-intensive and cannot be conducted continuously. OBJECTIVE: This study aimed to predict the onset of late-onset sepsis (LOS) with good diagnostic value as early as possible using non-invasive biosignal measurements from neonatal intensive care unit (NICU) monitors. METHODS: In this prospective multicenter study, we developed a multimodal machine learning algorithm based on a convolutional neural network (CNN) structure that uses the power spectral density (PSD) of recorded biosignals to predict the onset of LOS. This approach aimed to discern LOS-related pathogenic spectral signatures without labor-intensive manual artifact removal. RESULTS: The model achieved an area under the receiver operating characteristic score of 0.810 (95 % CI 0.698-0.922) on the validation dataset. With an optimal operating point, LOS detection had 83 % sensitivity and 73 % specificity. The median early detection was 44 h before clinical suspicion. The results highlighted the additive importance of electrocardiogram and respiratory impedance (RESP) signals in improving predictive accuracy. According to a more detailed analysis, the predictive power arose from the morphology of the electrocardiogram's R-wave and sudden changes in the RESP signal. CONCLUSION: Raw biosignals from NICU monitors, in conjunction with PSD transformation, as input to the CNN, can provide state-of-the-art prediction performance for LOS without the need for artifact removal. To the knowledge of the authors, this is the first study to highlight the independent and additive predictive potential of electrocardiogram R-wave morphology and concurrent, sudden changes in the RESP waveform in predicting the onset of LOS using non-invasive biosignals.

The Sensitivity and Specificity of Procalcitonin in Diagnosing Bacterial Sepsis in Neonates.

CONTEXT AND OBJECTIVES: Neonatal sepsis accounts for 15% of all neonatal deaths. Early detection enables prompt administration of antibiotic treatment, reducing morbidity and mortality. This study aims to review the sensitivity and specificity of procalcitonin in diagnosing microbiologically-proven sepsis in neonates to determine the optimal procalcitonin cut-off value for use in clinical practice. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Medline, EMBASE and PubMed were searched on 3 May 2023 for original studies in symptomatic neonates in whom both blood culture and procalcitonin levels were taken, and a procalcitonin cut-off with either sensitivity or specificity reported. Studies that included asymptomatic or culture-negative neonates in the proven sepsis group were excluded. Risk of bias was assessed using the Qualitative Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Nineteen original studies enrolling a total of 1920 symptomatic neonates (721 with proven sepsis) were included. Six studies used a procalcitonin cut-off of 0.5 ng/mL and found a sensitivity of 87% to 100% and specificity of 17% to 89%. Nine studies evaluated higher procalcitonin cut-off values between 0.99 ng/mL and 2 ng/mL, which were 67% to 98% sensitive and 41% to 89% specific. All other procalcitonin thresholds were neither sensitive nor specific. Meta-analysis was not performed because of high risk of bias within the identified studies. CONCLUSIONS: This review found that procalcitonin was highly sensitive (87% to 100%) at a cut-off value of 0.5 ng/mL, although specificity varied greatly across all cut-off values reviewed. The variation in diagnostic accuracy between studies suggests that procalcitonin may be useful to guide antibiotic cessation but should not be used alone as a diagnostic marker for neonatal sepsis.

Maternal biomarkers in predicting neonatal sepsis after preterm premature rupture of membranes in preterm infants.

AIM: This retrospective cohort study aimed to assess the utility of maternal C-reactive protein (CRP) and leukocyte levels in predicting neonatal sepsis after preterm premature rupture of membranes (pPROM). METHODS: We conducted a retrospective cohort study (2009-2021), encompassing preterm infants born ≤29 + 6 weeks of gestation following pPROM. The primary outcome was early-onset neonatal sepsis within the initial 72 h of life. RESULTS: We analysed data from 706 patients with a median gestational age at pPROM of 25.1 weeks and a median gestational age at birth of 26.4 weeks. Overall survival rate was 86.1%, with 65.7% survival without severe morbidities. These rates were significantly worse in preterm infants with sepsis. Maternal CRP and leukocyte levels correlated significantly with neonatal infection markers and sepsis. However, their predictive values, correlation coefficients, and area under the curve values were generally low. Using maternal CRP ≥2 mg/dL to predict neonatal sepsis yielded a positive predictive value of 18.5%, negative predictive value of 91.5%, AUC of 0.589, 45.5% sensitivity, and 74.5% specificity. CONCLUSION: Maternal CRP and leukocyte levels were ineffective as a tool for predicting early-onset neonatal sepsis following early pPROM. Consequently, these biomarkers lack the reliability required for clinical decision-making in this context.

Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study.

BACKGROUND: Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition. METHODS: The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as "Confirmed LOS": positive blood culture - microorganism isolated and LOS symptoms, "Unconfirmed LOS": negative blood culture and LOS symptoms, and "Controls" group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression. RESULTS: A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as "Confirmed LOS", and "unconfirmed LOS" cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01-1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07-1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13-10.25). CONCLUSIONS: The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.

Exploration of programmed cell death-associated characteristics and immune infiltration in neonatal sepsis: new insights from bioinformatics analysis and machine learning.

BACKGROUND: Neonatal sepsis, a perilous medical situation, is typified by the malfunction of organs and serves as the primary reason for neonatal mortality. Nevertheless, the mechanisms underlying newborn sepsis remain ambiguous. Programmed cell death (PCD) has a connection with numerous infectious illnesses and holds a significant function in newborn sepsis, potentially serving as a marker for diagnosing the condition. METHODS: From the GEO public repository, we selected two groups, which we referred to as the training and validation sets, for our analysis of neonatal sepsis. We obtained PCD-related genes from 12 different patterns, including databases and published literature. We first obtained differential expressed genes (DEGs) for neonatal sepsis and controls. Three advanced machine learning techniques, namely LASSO, SVM-RFE, and RF, were employed to identify potential genes connected to PCD. To further validate the results, PPI networks were constructed, artificial neural networks and consensus clustering were used. Subsequently, a neonatal sepsis diagnostic prediction model was developed and evaluated. We conducted an analysis of immune cell infiltration to examine immune cell dysregulation in neonatal sepsis, and we established a ceRNA network based on the identified marker genes. RESULTS: Within the context of neonatal sepsis, a total of 49 genes exhibited an intersection between the differentially expressed genes (DEGs) and those associated with programmed cell death (PCD). Utilizing three distinct machine learning techniques, six genes were identified as common to both DEGs and PCD-associated genes. A diagnostic model was subsequently constructed by integrating differential expression profiles, and subsequently validated by conducting artificial neural networks and consensus clustering. Receiver operating characteristic (ROC) curves were employed to assess the diagnostic merit of the model, which yielded promising results. The immune infiltration analysis revealed notable disparities in patients diagnosed with neonatal sepsis. Furthermore, based on the identified marker genes, the ceRNA network revealed an intricate regulatory interplay. CONCLUSION: In our investigation, we methodically identified six marker genes (AP3B2, STAT3, TSPO, S100A9, GNS, and CX3CR1). An effective diagnostic prediction model emerged from an exhaustive analysis within the training group (AUC 0.930, 95%CI 0.887-0.965) and the validation group (AUC 0.977, 95%CI 0.935-1.000).

Micromotor-based dual aptassay for early cost-effective diagnosis of neonatal sepsis.

Given the long-life expectancy of the newborn, research aimed at improving sepsis diagnosis and management in this population has been recognized as cost-effective, which at early stages continues to be a tremendous challenge. Despite there is not an ideal-specific biomarker, the simultaneous detection of biomarkers with different behavior during an infection such as procalcitonin (PCT) as high specificity biomarker with one of the earliest biomarkers in sepsis as interleukin-6 (IL-6) increases diagnostic performance. This is not only due to their high positive predictive value but also, since it can also help the clinician to rule out infection and thus avoid the use of antibiotics, due to their high negative predictive value. To this end, we explore a cutting-edge micromotor (MM)-based OFF-ON dual aptassay for simultaneous determination of both biomarkers in 15 min using just 2 µL of sample from low-birth-weight neonates with gestational age less than 32 weeks and birthweight below 1000 g with clinical suspicion of late-onset sepsis. The approach reached the high sensitivities demanded in the clinical scenario (LODPCT = 0.003 ng/mL, LODIL6 = 0.15 pg/mL) with excellent correlation performance (r > 0.9990, p < 0.05) of the MM-based approach with the Hospital method for both biomarkers during the analysis of diagnosed samples and reliability (Er < 6% for PCT, and Er < 4% for IL-6). The proposed approach also encompasses distinctive technical attributes in a clinical scenario since its minimal sample volume requirements and expeditious results compatible with few easy-to-obtain drops of heel stick blood samples from newborns admitted to the neonatal intensive care unit. This would enable the monitoring of both sepsis biomarkers within the initial hours after the manifestation of symptoms in high-risk neonates as a valuable tool in facilitating prompt and well-informed decisions about the initiation of antibiotic therapy.These results revealed the asset behind micromotor technology for multiplexing analysis in diagnosing neonatal sepsis, opening new avenues in low sample volume-based diagnostics.

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Game changer or gimmick: inflammatory markers to guide antibiotic treatment decisions in neonatal early-onset sepsis.

BACKGROUND: The diagnosis of neonatal early-onset sepsis (EOS) is challenging, and inflammatory markers are widely used to guide decision-making and therapies. OBJECTIVES: This narrative review presents the current state of knowledge regarding the diagnostic value and potential pitfalls in the interpretation of inflammatory markers for EOS. SOURCES: PubMed until October 2022 and searched references in identified articles using the search terms: neonatal EOS, biomarker or inflammatory marker, and antibiotic therapy or antibiotic stewardship. CONTENT: In situations with a high or low probability of sepsis, the measurements of inflammatory markers have no impact on the decision to start or stop antibiotics and are just gimmick, whereas they may be a game changer for neonates with intermediate risk and therefore an unclear situation. There is no single or combination of inflammatory markers that can predict EOS with high probability, allowing us to make decisions regarding the start of antibiotics based only on inflammatory markers. The main reason for the limited accuracy is most probably the numerous noninfectious conditions that influence the levels of inflammatory markers. However, there is evidence that C-reactive protein and procalcitonin have good negative predictive accuracy to rule out sepsis within 24 to 48 hours. Nevertheless, several publications have reported more investigations and prolonged antibiotic treatments with the use of inflammatory markers. Given the limitations of current strategies, using an algorithm with only moderate diagnostic accuracy may have a positive impact, as reported for the EOS calculator and the NeoPInS algorithm. IMPLICATIONS: As the decision regarding the start of antibiotic therapy is different from the process of stopping antibiotics, the accuracy of inflammatory markers needs to be evaluated separately. Novel machine learning-based algorithms are required to improve accuracy in the diagnosis of EOS. In the future, inflammatory markers included in algorithms may be a game changer reducing bias and noise in the decision-making process.

Enhanced Category-Based Risk Assessment for Neonatal Early-Onset Sepsis: A Prospective Observational Study.

INTRODUCTION: Compared with multivariate risk assessment, traditional category-based risk assessment (CRA) approaches for neonatal early-onset sepsis (EOS) screening are usually straightforward to use, do not require electronic devices, but are associated with higher rates of antibiotic use. This study aims to evaluate the performance of a novel enhanced CRA (eCRA) framework on EOS admissions and antibiotic use and to investigate whether a modified version with adjustments in risk factor weighting can allow its performance to match the EOS calculator while remaining easy to implement. METHOD: This is a prospective, single-center, two-phase observational study. Infants of all gestations delivered in a tertiary hospital in Hong Kong with risk factors or clinical features of EOS were recruited. PHASE I: A novel eCRA framework (period 2) was compared with the CDC 2010-based protocol (period 1). PHASE II: A modified eCRA framework was compared theoretically with the EOS calculator. EOS-specific admissions and antibiotic use were measured. RESULTS: Phase I: 1,025 at-risk infants were recruited during period 2 and compared with 757 infants of period 1. Admissions and antibiotic use decreased from 45.8% to 29.4% and 41.1% to 28.2%, respectively. Antibiotics among those at-risk but well-appearing infants decreased from 25.3% to 16.3% (p < 0.001 for all). PHASE II: antibiotic use was similar (7.3 vs. 6.4%, p = 0.42) between the modified eCRA framework and the EOS calculator. CONCLUSIONS: An eCRA framework can effectively and safely provide individualized guidance for EOS screening without the need for tools such as the EOS calculator.

Umbilical cord blood hematological parameters in predicting early onset neonatal sepsis (EOS) - a prospective cohort study.

OBJECTIVES: In low and middle income countries, there is a need for affordable and accurate biomarkers to identify neonates at risk of early onset neonatal sepsis (EOS). Cord blood hematological parameters if reliable and accurate for the detection of EOS are cost effective and can reduce the need for repeated venipuncture in the neonate. METHODS: In this prospective cohort study, the umbilical cord parameters of newborns with gestational age >34 weeks were collected. These neonates were followed up for 72 h and septic screen was employed in those babies who had risk factors or developed clinical features of sepsis. The cord blood parameters of the normal newborn and those who had sepsis were analyzed. RESULTS: A total of 513 neonates were enrolled for the study, 32 required septic screening of whom 13 neonates were found to meet the criteria for sepsis: either blood culture positive or sepsis screen positive with clinical features. Cord blood parameters were analyzed using independent t test. Red cell distribution width (RDW) and band cells were statistically significant (p 0.007 and 0.009 respectively) between the septic and normal neonates. Increased RDW had a sensitivity of 61.54 %, specificity of 54.60 %. Increased band cells with a cut off of >15 cells had a sensitivity of 7.7 % with specificity of 100 % with higher numbers in septic neonates. Increased RDW and band cells in combination had sensitivity of 61.54 % and specificity of 54.6 %. CONCLUSIONS: RDW and band cell can be potential markers of EOS in cord blood but require further study in a larger population.