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AIM: The aim of this study is to investigate the utility of interleukin-6 (IL-6) in the early diagnosis of serious bacterial infections (SBI) in febrile infants and to compare it with C-reactive protein (CRP). METHODS: Retrospective study conducted in the paediatric emergency department in Gothenburg, Sweden, on previously healthy, full-term infants aged ≤60 days with fever without a source (FWS) from 2014 to 2017. RESULTS: We included 536 infants with FWS, of whom IL-6 was analysed in 364 (68%) and CRP was analysed in 494 (92%). Approximately 70% of the infants presented with a fever duration of less than 12 h. The prevalence of SBIs was 14.8% (95% CI,11.3-18.9) in the IL-6 group and 17.8% (95% CI,14.5-21.5) in the CRP group. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of IL-6 ≥50 ng/L were 93%, 66%, 98% and 33%, respectively. For CRP ≥20 mg/L, the sensitivity, specificity, NPV, and PPV were 76%, 89%, 95%, and 55%, respectively. Logistic regression analysis showed that CRP was significantly associated with SBI (p < 0.0001) in the entire population, whereas IL-6 was not. CONCLUSION: Interleukin-6 showed high sensitivity and NPV, which might assist in identifying SBIs early in febrile infants. However, IL-6 was not shown to be superior to CRP and further studies are needed to investigate whether IL-6 should be incorporated in clinical management.

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Background: Management of young febrile infants is challenging. Therefore, several guidelines have been developed over the last decades. However, knowledge regarding the impact of introducing guidelines for febrile infants is limited. We assessed the impact of and adherence to a novel guideline for managing febrile infants aged ≤59 days. Methods: This retrospective cross-sectional study was conducted in 2 pediatric emergency departments in Sweden between 2014 and 2021. We compared the management of infants aged ≤59 days with fever without a source (FWS) and the diagnosis of serious bacterial infections (SBIs) before and after implementing the new guideline. Results: We included 1,326 infants aged ≤59 days with FWS. Among infants aged ≤21 days, urine cultures increased from 49% to 67% (p = 0.001), blood cultures from 43% to 63% (p < 0.001), lumbar punctures from 16% to 33% (p = 0.003), and antibiotics from 38% to 57% (p = 0.002). Only 39 of 142 (28%) infants aged ≤21 days received recommended management. The SBI prevalence was 16.7% (95% CI, 11.0-23.8) and 17.6% (95% CI, 11.7-24.9) before and after the implementation, respectively. Among infants aged ≤59 days, there were 3 infants (0.6%; 95% CI, 0.1-1.7) in the pre-implementation period and 3 infants (0.6%; 95% CI, 0.1-1.7) in the post-implementation period with delayed treated urinary tract infections. Conclusions: Investigations and antibiotics increased significantly after implementation of the new guideline. However, doing more did not improve the diagnosis of SBIs. Thus, the low adherence to the new guideline may be considered justified. Future research should consider strategies to safely minimize interventions when managing infants with FWS.

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BACKGROUND: Pakistan reports a significant burden of neonatal mortality, with infections as one of the major causes. We aim to assess the long-term impact of early infancy infections on neurodevelopmental outcomes during later childhood. METHODS: We conducted a prospective follow-up study of the cohort enrolled at the Karachi site of the Aetiology of Neonatal Infection in South Asia (ANISA) during 2019-2020. Children with a possible serious bacterial infection (based on the WHO IMCI algorithm) at early infancy were assessed for neurodevelopment at 6-9 years of age and compared with healthy controls. The Ten Questions (TQS) questionnaire, Strengths and Difficulties Questionnaire (SDQ), and Parent's Evaluation of Developmental Stage Assessment Level (PEDS: DM-AL) neurodevelopmental assessment tools, were administered and scored by the research staff who were blinded to the child's exposure status. Generalized Structural Equation Modelling (GSEM) was employed to verify relationships and associations among developmental milestones, anthropometry, and sociodemographic variables. RESULTS: A total of 398 children (241 cases and 157 controls) completed neurodevelopmental and growth assessments. Cases had a significantly higher rate of abnormal TQS scores (54.5% vs. 35.0%, p-value 0.001), greater delays in motor milestones (21.2% vs. 12.1%, p-value 0.02), lower fine motor skills (78.4 ± 1.4 vs. 83.2 ± 1.5, p-value 0.02). The receptive language skills were well-developed in both groups. According to the logistic regression model, exposure to infection during the first 59 days of life was associated with delayed TQS milestones (ß = -0.6, 95% CI -1.2,-0.04), TQS hearing domain (ß = -0.3, 95% CI: -1.2 to 0.7), PEDS: DM-AL fine motor domain (ß = -1.3, 95% CI: -4.4 to 1.7), PEDS: DM-AL receptive language development (ß = -1.1, 95% CI: -3.7 to 1.4) and child anthropometric measurements such as weight and height (ß = -0.2, 95% CI: -0.4 to 0.01 and ß = -0.2, 95% CI: -0.4 to -0.01, respectively). Early pSBI exposure was positively associated with PEDS: DM-AL self-help domain (ß = 0.6, 95% CI: -1.2 to 2.4) and SDQ-P overall score (ß = 0.02, 95% CI: -0.3 to 0.3). CONCLUSION: Children exposed to PSBI during early infancy have higher rates of abnormal development, motor delays, and lower fine motor skills during later childhood in Pakistan. Socioeconomic challenges and limited healthcare access contribute to these challenges, highlighting the need for long-term follow-ups with integrated neurodevelopment assessments.

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Introduction: Procalcitonin (PCT) is a useful biomarker in the initial evaluation of febrile infants for serious bacterial infections (SBIs). However, PCT is not always available locally and must at times be frozen and shipped to a reference laboratory for research studies. We sought to compare PCT measured locally versus centrally at a reference laboratory during a research study. Materials and methods: This was a secondary analysis of a multicenter study of febrile infants ≤60 days evaluated for SBIs from June 2016 to April 2019. A PCT cutoff value of 0.5 ng/mL was used to stratify infants at low-versus high-risk of SBIs. Statistical analyses consisted of Spearman's correlation, Bland-Altman difference plotting, Passing-Bablok regression, Deming regression, and Fisher's exact testing at the 0.5 ng/mL threshold. Results: 241 febrile infants had PCT levels measured both locally and at the reference laboratory. PCT levels measured locally on 5 different platforms and from the frozen research samples demonstrated strong Spearman's correlation (ρ = 0.83) and had similar mean PCT values with an average relative difference of 0.02%. Eleven infants with SBIs had PCT values < 0.5 ng/mL in both the clinical and research samples. Six other infants had differences in SBI prediction based on PCT values at the 0.5 ng/mL threshold between the clinical and research platforms. Conclusions: We found no significant differences in detection of febrile infants at high risk for SBI based on locally (on multiple platforms) versus centrally processed PCT. Testing at a central reference laboratory after freezing and shipping is an accurate and reliable alternative for research studies or when rapid turnaround is not required.

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Objectives: Hyperpyrexia has been associated with a greater prevalence of bacterial infections in the pediatric population, which prior to routine childhood vaccinations, has led to invasive testing and empiric antibiotic use for urinary tract infections, bacterial pneumonia, bacteremia, and bacterial meningitis. Since the implementation of routine childhood vaccinations, the prevalence of serious bacterial infections (SBIs) has declined. This study aims to determine if there is an association between hyperpyrexia and serious bacterial infections in well-appearing febrile pediatric patients presenting to the emergency department (ED). Methods: This is a cross-sectional study conducted between January 1, 2019, and December 31, 2019, at a single urban tertiary care pediatric ED. Patients were included if they were between 61 days and ≤18 years old presenting with a chief complaint of fever. Patients were excluded if they received antibiotics within 3 days of presentation, underwent surgical procedures within 2 weeks of presentation, had an ED visit for febrile illness within 2 weeks of study visit, were transferred from another institution, or were ill appearing. Prevalence of SBI was described and compared by presence of hyperpyrexia, age group, chronic medical condition, gender, and vaccination status. Logistic regression was used to analyze the association between SBIs and hyperpyrexia. Results: Of the 3862 charts reviewed, 2565 patients were included. The prevalence of SBI was 5.6%. A total of 413 patients presented with hyperpyrexia. Of the patients with hyperpyrexia, 31 (7.5%) had a serious bacterial infection. Hyperpyrexia was not significantly associated with SBIs in our logistic regression models (adjusted Odds Ratio 1.40, 95% confidence interval 0.92-2.12). Conclusions: Serious bacterial infections were uncommon in our population. There is no statistically significant association between hyperpyrexia and SBIs in well-appearing pediatric patients presenting to the ED with fever. The lack of a statistically significant association between hyperpyrexia and SBIs argues that clinicians should be cautious using hyperpyrexia as an independent risk factor for SBIs. More research is needed to identify independent and grouped SBI risk factors in well-appearing pediatric patients presenting to the ED.

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BACKGROUND: Ethiopia and Kenya have adopted the community-based integrated community case management (iCCM) of common childhood illnesses and newborn care strategy to improve access to treatment of infections in newborns and young infants since 2012 and 2018, respectively. However, the iCCM strategy implementation has not been fully integrated into the health system in both countries. This paper describes the extent of integration of iCCM program at the district/county health system level, related barriers to optimal integration and implementation of strategies. METHODS: From November 2020 to August 2021, Ethiopia and Kenya implemented the community-based treatment of possible serious bacterial infection (PSBI) when referral to a higher facility is not possible using embedded implementation research (eIR) to mitigate the impact of COVID-19 on the delivery of this life-saving intervention. Both projects conducted mixed methods research from April-May 2021 to identify barriers and facilitators and inform strategies and summative evaluations from June-July 2022 to monitor the effectiveness of implementation outcomes including integration of strategies. RESULTS: Strategies identified as needed for successful implementation and sustainability of the management of PSBI integrated at the primary care level included continued coaching and support systems for frontline health workers, technical oversight from the district/county health system, and ensuring adequate supply of commodities. As a result, support and technical oversight capacity and collaborative learning were strengthened between primary care facilities and community health workers, resulting in improved bidirectional linkages. Improvement of PSBI treatment was seen with over 85% and 81% of estimated sick young infants identified and treated in Ethiopia and Kenya, respectively. However, perceived low quality of service, lack of community trust, and shortage of supplies remained barriers impeding optimal PSBI services access and delivery. CONCLUSION: Pragmatic eIR identified shared and unique contextual challenges between and across the two countries which informed the design and implementation of strategies to optimize the integration of PSBI management into the health system during the COVID-19 pandemic. The eIR participatory design also strengthened ownership to operationalize the implementation of identified strategies needed to improve the health system's capacity for PSBI treatment.

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The evaluation and management of young infants presenting with fever remains an area of significant practice variation. While most well-appearing febrile young infants have a viral illness, identifying those at risk for invasive bacterial infections, specifically bacteremia and bacterial meningitis, is critical. This statement considers infants aged ≤90 days who present with a rectal temperature ≥38.0°C but appear well otherwise. Applying recent risk-stratification criteria to guide management and incorporating diagnostic testing with procalcitonin are advised. Management decisions for infants meeting low-risk criteria should reflect the probability of disease, consider the balance of risks and potential harm, and include parents/caregivers in shared decision-making when options exist. Optimal management may also be influenced by pragmatic considerations, such as access to diagnostic investigations, observation units, tertiary care, and follow-up. Special considerations such as temperature measurement, risk for invasive herpes simplex infection, and post-immunization fever are also discussed.

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Febrile infections in children are a common cause of presentation to the emergency department (ED). While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; nowadays, a better understanding of immunochemical pathways has led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models, combining them for serious bacterial infection (SBI) diagnosis in febrile children. Literature analysis shows that inflammatory response is a complex mechanism in which many biochemical and immunological factors contribute to the host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined, and for this reason, it is reasonable to take them both into consideration in the evaluation of febrile children. The potential of machine learning tools, which represent a real novelty in medical practice, in conjunction with routine clinical and biological information, may improve the accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pediatric precision medicine still uncertain. More data from further research are needed to improve clinical practice and decision making using these new technologies.

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We aimed to assess the prevalence of serious bacterial infections (SBIs) in febrile infants < 90 days of age with SARS-CoV-2 infection versus SARS-CoV-2-negative febrile infants. A retrospective cohort study was conducted in a tertiary pediatric emergency department between March 2020 and October 2022. Febrile infants < 90 days of age who underwent SARS-CoV-2 testing were included. SBIs were defined as urinary tract infection (UTI), bacteremia, and/or bacterial meningitis; bacteremia and bacterial meningitis were considered invasive bacterial infections (IBIs). SBIs rates were compared between SARS-CoV-2-positive and negative infants and stratified by age. We included 779 infants: 221 (28.4%) SARS-CoV-2-positive and 558 (71.6%) SARS-CoV-2-negative. The SBI rate in the SARS-CoV-2-positive group was 5.9% vs 22.9% in the SARS-CoV-2-negative group (p < 0.001; relative risk (RR) 0.26; [95% CI 0.15-0.44]); the most common infections were UTI (5.4% vs 22.0%; p < 0.001). The IBI rate was 0.5% in the SARS-CoV-2-positive group vs. 3.2% in the negative group (p = 0.024; RR 0.14 [95% CI 0.02-1.04]). There were no cases of bacterial meningitis in the positive infants. SARS-CoV-2-positive infants > 28 days of age had a decreased likelihood of SBI (RR 0.22 [95% CI 0.11-0.43]), with no cases of IBI identified.     Conclusions: Febrile infants < 90 days of age with SARS-CoV-2 infection are at significantly lower risk of SBIs than those who are SARS-CoV-2-negative. Nevertheless, the rate of UTI remains considerable in SARS-CoV-2-positive infants. SARS-CoV-2 detection may be relevant in considering IBI risk for well-appearing febrile infants 29-89 days of age. What is Known: • Febrile infants with laboratory-confirmed viral infections have a significantly lower risk of serious bacterial infections when compared to those without them. Data focusing on very young febrile infants with a SARS-CoV-2 infection is still limited. What is New: • Young febrile infants with SARS-CoV-2 infection are at significantly lower risk of serious bacterial infections than those who are SARS-CoV-2-negative. Nevertheless, the rate of urinary tract infection remains considerable. SARS-CoV-2 detection may be relevant in considering invasive bacterial infection risk for well-appearing febrile infants 29-89 days of age.

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BACKGROUND: Serious bacterial infections (SBIs) are linked to unplanned hospital admissions and a high mortality rate. The early identification of SBIs is crucial in clinical practice. OBJECTIVE: This study aims to establish and validate clinically applicable models designed to identify SBIs in patients with infective fever. METHODS: Clinical data from 945 patients with infective fever, encompassing demographic and laboratory indicators, were retrospectively collected from a 2200-bed teaching hospital between January 2013 and December 2020. The data were randomly divided into training and test sets at a ratio of 7:3. Various machine learning (ML) algorithms, including Boruta, Lasso (least absolute shrinkage and selection operator), and recursive feature elimination, were utilized for feature filtering. The selected features were subsequently used to construct models predicting SBIs using logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost) with 5-fold cross-validation. Performance metrics, including the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC), accuracy, sensitivity, and other relevant parameters, were used to assess model performance. Considering both model performance and clinical needs, 2 clinical timing-sequence warning models were ultimately confirmed using LR analysis. The corresponding predictive nomograms were then plotted for clinical use. Moreover, a physician, blinded to the study, collected additional data from the same center involving 164 patients during 2021. The nomograms developed in the study were then applied in clinical practice to further validate their clinical utility. RESULTS: In total, 69.9% (661/945) of the patients developed SBIs. Age, hemoglobin, neutrophil-to-lymphocyte ratio, fibrinogen, and C-reactive protein levels were identified as important features by at least two ML algorithms. Considering the collection sequence of these indicators and clinical demands, 2 timing-sequence models predicting the SBI risk were constructed accordingly: the early admission model (model 1) and the model within 24 hours of admission (model 2). LR demonstrated better stability than RF and XGBoost in both models and performed the best in model 2, with an AUC, accuracy, and sensitivity of 0.780 (95% CI 0.720-841), 0.754 (95% CI 0.698-804), and 0.776 (95% CI 0.711-832), respectively. XGBoost had an advantage over LR in AUC (0.708, 95% CI 0.641-775 vs 0.686, 95% CI 0.617-754), while RF achieved better accuracy (0.729, 95% CI 0.673-780) and sensitivity (0.790, 95% CI 0.728-844) than the other 2 approaches in model 1. Two SBI-risk prediction nomograms were developed for clinical use based on LR, and they exhibited good performance with an accuracy of 0.707 and 0.750 and a sensitivity of 0.729 and 0.927 in clinical application. CONCLUSIONS: The clinical timing-sequence warning models demonstrated efficacy in predicting SBIs in patients suspected of having infective fever and in clinical application, suggesting good potential in clinical decision-making. Nevertheless, additional prospective and multicenter studies are necessary to further confirm their clinical utility.

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OBJECTIVES: We aimed to evaluate the impact of respiratory symptoms and positive viral testing on the risk of serious bacterial infections (SBIs). METHODS: A retrospective study was conducted that included infants (0-60 days) presenting with a fever between 2001 and 2022 at a tertiary hospital in northern Israel. Demographic, clinical, and laboratory parameters were collected, and risk factors for SBIs were analyzed. RESULTS: Data from a total of 3106 infants, including data from blood, urine, and CSF cultures, were obtained in 96.6%, 89%, and 29% of cases, respectively. A fever without respiratory symptoms (fever only) was present in 1312 infants, while 1794 had a fever and respiratory symptoms-427 were positive for a respiratory virus (virus+), 759 tested negative (virus-), and 608 were not tested. The SBI rate was 5.1% vs. 7.5% in the fever-and-respiratory group vs. the fever-only group (p = 0.004, OR = 0.65 (95% CI = 0.49-0.88)) and 2.8% vs. 7% in the virus+ vs. virus- group (p = 0.002, OR = 0.385, (95% CI = 0.203-0.728)). The male gender, an age < 1 month, leukocytosis > 15 × 109/L, or a CRP > 2 mg/dL increased the risk of SBIs. Respiratory symptoms or a confirmed viral infection reduced the risk of SBIs in the presence of the above risk factors. CONCLUSIONS: Respiratory symptoms and a positive viral test decreased the risk of SBIs. Combining rapid viral testing with clinical variables may identify low-risk infants. Despite the relatively low risk of SBIs in individuals with viral infections, conducting prospective studies remains essential for accurately predicting the occurrence of these potentially life-threatening infections.

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Adjusting the chronological age of preterm infants according to their gestational age is a widely accepted practice in the field of neurodevelopment. It has been suggested for the assessment of preterm infants with suspected infection, but has been poorly validated. Correcting for chronological age is especially critical in infants with a chronological age above 3 months, but a corrected age below 3 months due to the differences in assessment protocols. This study assessed the difference in incidence of serious bacterial infection (SBI) according to chronological and corrected age in preterm infants. A retrospective analysis of pediatric emergency department (PED) presentations was conducted for all 448 preterm infants born in between January 2010 and August 2019. Of the 448 preterm infants, 204 (46%) presented at one of 3 PEDs in Jerusalem, Israel, during their first year of life. Overall, 141 (31.4%) presented with fever and were included in the study. The infants were divided into 3 age groups: 1-corrected age >3 months; 2-chronological age >3 months, but corrected age <3 months; 3-chronological and corrected age <3 months. SBI was diagnosed in 2.6%, 16.7%, and 33.3% of the infants in groups 1, 2 and 3, respectively; (p < 0.01, p = 0.17, p < 0.001). The incidence of SBI in the control group of 300 term infants <3 months presenting to the PED due to fever was 15.3%. Preterm infants with a corrected age <3 months are at increased risk for SBI, similarly to term infants <3 months of age. Age correction should thus be considered for preterm infants presenting with fever.

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Objectives: Procalcitonin testing is recommended to discriminate febrile young infants at risk of serious bacterial infections (SBI). However, this test is not available in many clinical settings, limited largely by cost. This study sought to evaluate contemporary real-world costs associated with the usual care of febrile young infants, and estimate impact on clinical trajectory and costs when incorporating procalcitonin testing. Methods: We assessed hospital-level door-to-discharge costs of all well-appearing febrile infants aged ≤60 days, evaluated at a tertiary paediatric hospital between April/2016 and March/2019. Emergency Department and inpatient expense data for usual care were obtained from the institutional general ledger, validated by the provincial Ministry of Health. These costs were then incorporated into a probabilistic model of risk stratification for an equivalent simulated cohort, with the addition of procalcitonin. Results: During the 3-year study period, 1168 index visits were included for analysis. Real-world median costs-per-infant were the following: $3266 (IQR $2468 to $4317, n=93) for hospitalized infants with SBIs; $2476 (IQR $1974 to $3236, n=530) for hospitalized infants without SBIs; $323 (IQR $286 to $393, n=538) for discharged infants without SBIs; and, $3879 (IQR $3263 to $5297, n=7) for discharged infants subsequently hospitalized for missed SBIs. Overall median cost-per-infant of usual care was $1555 (IQR $1244 to $2025), compared to a modelled cost of $1389 (IQR $1118 to $1797) with the addition of procalcitonin (10.7% overall cost savings; $1,816,733 versus $1,622,483). Under pessimistic and optimistic model assumptions, savings were 5.9% and 14.9%, respectively. Conclusions: Usual care of febrile young infants is variable and resource intensive. Increased access to procalcitonin testing could improve risk stratification at lower overall costs.

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Clinical algorithms used in the assessment of febrile children in the Paediatric Emergency Departments are commonly based on threshold values for vital signs, which in children with fever are often outside the normal range. Our aim was to assess the diagnostic value of heart and respiratory rate for serious bacterial infection (SBI) in children after temperature lowering following administration of antipyretics. A prospective cohort of children presenting with fever between June 2014 and March 2015 at the Paediatric Emergency Department of a large teaching hospital in London, UK, was performed. Seven hundred forty children aged 1 month-16 years presenting with a fever and ≥ 1 warning signs of SBI given antipyretics were included. Tachycardia or tachypnoea were defined by different threshold values: (a) APLS threshold values, (b) age-specific and temperature-adjusted centiles charts and (c) relative difference in z-score. SBI was defined by a composite reference standard (cultures from a sterile site, microbiology and virology results, radiological abnormalities, expert panel). Persistent tachypnoea after body temperature lowering was an important predictor of SBI (OR 1.92, 95% CI 1.15, 3.30). This effect was only observed for pneumonia but not other SBIs. Threshold values for tachypnoea > 97th centile at repeat measurement achieved high specificity (0.95 (0.93, 0.96)) and positive likelihood ratios (LR + 3.25 (1.73, 6.11)) and may be useful for ruling in SBI, specifically pneumonia. Persistent tachycardia was not an independent predictor of SBI and had limited value as a diagnostic test.  Conclusion: Among children given antipyretics, tachypnoea at repeat measurement had some value in predicting SBI and was useful to rule in pneumonia. The diagnostic value of tachycardia was poor. Overreliance on heart rate as a diagnostic feature following body temperature lowering may not be justified to facilitate safe discharge. What is Known: • Abnormal vital signs at triage have limited value as a diagnostic test to identify children with SBI, and fever alters the specificity of commonly used threshold values for vital signs. • The observed temperature response after antipyretics is not a clinically useful indicator to differentiate the cause of febrile illness. What is New: • Persistent tachycardia following reduction in body temperature was not associated with an increased risk of SBI and of poor value as a diagnostic test, whilst persistent tachypnoea may indicate the presence of pneumonia.

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BACKGROUND: Non-polio enterovirus aseptic meningitis (NPE-AM) is a self-limiting illness that can mimic serious bacterial infection (SBI) in infants during their first months of life. OBJECTIVES: To compare the clinical features of febrile infants diagnosed with NPE-AM with those of infants who had SBI or non-bacterial infection (NBI). STUDY DESIGN: A systematic series of febrile infants < 3-months-old hospitalized between 2010 and 2019 with febrile illness in a tertiary hospital. Clinical and laboratory data were compared between the three groups. RESULTS: Overall 1278 infants were included; 207 (16.2%) had NPE-AM, 210 (16.4%) SBI and 861 (67.4%) NBI. The median age was 34 (IQR: 21.5-51.7) days. NPE-AM was documented in 25% of infants < 29 days and 9.9% of infants aged 29-90 days. Infants with NPE-AM or SBI had fever >39°C more frequently, 24.2% and 17.1% compared with 10% in infants with NBI (p < 0.001). Fever duration ≥ 2 days was reported in 3.4% of infants with NPE-AM vs 18.6% in SBI and 26.3% in NBI (p < 0001); rash occurred in 37.7% in NPE-AM compared to 4.6% in NBI and 5.7% in SBI (p < 0.001). The mean white blood count, C-reactive protein and absolute neutrophil count were significantly lower in infants with NPE-AM compared to infants with the SBI (p < 0.001) and similar to the means in infants with NBI (p = 0.848, 0.098 and 0.764 respectively). A high proportion of bloody tap 346/784 (53.1%) was detected. Infants with NPE-AM were more likely to be treated with antibiotics than infants with NBIs (88.9% vs 50.7%, p < 0.001), similarly to infants with SBIs (p = 0.571). CONCLUSIONS: The clinical presentation of infants with NPE-AM that could mimic bacterial infection and the high rate of bloody taps may lead to more hospital admissions and antibiotic prescriptions. Rapid molecular testing for detection of NPE may be of additional value in the evaluation of febrile infants.

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AIM: To assess the performance of a new clinical decision rule (CDR) to identify patients at a low risk of invasive bacterial infection (IBI) among febrile children and its theoretical impact on antibiotic use. METHODS: Prospective study including consecutive children <5 years of age who presented in one French paediatric emergency department with fever without source between January and December 2016. With the collected data, we constructed a CDR based on a sequential approach based on age, clinical toxic signs, urinalysis and procalcitonin level. We evaluated its diagnostic performances to identify IBI and its potential impact on antibiotic use. RESULTS: Among the 1061 children (IBI 11/1061, 1.0%), 693 (65.3%) were classified at low or intermediate risk of IBI, with an IBI prevalence of 0%. The sensitivity and specificity of the CDR to predict IBI were 100% and 73.9%. Negative and positive predictive value were 100% and 3.9%, respectively. Using this new CDR, the current antibiotics exposure would theoretically be reduced from 33.6% to 24.1%. CONCLUSION: The promising interest of this clinical decision rule, using simple and accessible biological and clinical tools, needs to be confirm with an external validation study, which will allow its use in clinical practice.

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AIM: The COVID-19 omicron variant surge highlighted the evolving impact of COVID-19. Febrile infants <60 days old are high risk for serious bacterial infections (SBI). This study evaluated the rate of SBI based on COVID-19 infection. METHODS: We conducted a retrospective chart review at an urban, academic paediatric emergency department. The study enrolled infants 60 days old or less with documented fever. The primary outcome was SBI diagnosed by blood, urine, and/or cerebrospinal fluid cultures. We compared the rate of SBI between COVID-19 groups with an omicron variant and 29- to 60-day-old subgroup analyses. RESULTS: Two hundred and thirty-three (233) infants meet the criteria. The incidence of SBI was 18.7% in the COVID-19 negative and 1.7% in the COVID-19-positive group which is statistically significant (p < 0.001). Omicron subgroup analysis did not achieve statistical significance (p = 0.62) while COVID-19-positive infants 29-60 days old had a statistically significant lower rate of SBI (p = 0.006). CONCLUSION: The omicron variant surge provided an additional understanding of the impact of COVID-19 on these high-risk infants. These results can lead to decreased invasive testing and exposure to antibiotics as well as examine the utility of viral testing for risk stratification.

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BACKGROUND: The objective was to achieve high coverage of possible serious bacterial infections (PSBI) treatment using the World Health Organization (WHO) guideline for managing it on an outpatient basis when referral to a hospital is not feasible. METHODS: We implemented this guideline in the programme settings at 10 Basic Health Units (BHU) in two rural districts of Sindh in Pakistan using implementation research. A Technical Support Unit supported the programme to operationalize guidelines, built capacity of health workers through training, monitored their clinical skills, mentored them and assured quality. The community-based health workers visited households to identify sick infants and referred them to the nearest BHU for further management. The research team collected data. RESULTS: Of 17 600 identified livebirths, 1860 young infants with any sign of PSBI sought care at BHUs and 1113 (59.8%) were brought by families. We achieved treatment coverage of 95%, assuming an estimated 10% incidence of PSBI in the first 2 months of life and that 10% of young infants came from outside the study catchment area. All 923 infants (49%; 923/1860) 7-59 days old with only fast breathing (pneumonia) treated with outpatient oral amoxicillin were cured. Hospital referral was refused by 83.4% (781/937) families who accepted outpatient treatment; 92.2% (720/781) were cured and 0.8% (6/781) died. Twelve (7.6%; 12/156) died among those treated in a hospital. CONCLUSION: It is feasible to achieve high coverage by implementing WHO PSBI management guidelines in a programmatic setting when a referral is not feasible.

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Objective:To establish a mortality risk prediction model of severe bacterial infection in children and compare it with the pediatric early warning score (PEWS), pediatric critical illness score (PCIS) and pediatric risk of mortality score Ⅲ (PRISM Ⅲ).Methods:A total of 178 critically ill children were selected from the PICU of the Children's Hospital of Nanjing Medical University from May 2017 to June 2022. After obtaining the informed consent of the parents/guardians, basic information such as sex, age, height and weight, as well as indicators such as heart rate, systolic blood pressure and respiratory rate were collected from all children. A standard questionnaire was used to score the child 24 h after admission to the PICU. The children were divided into the survival and death groups according to their survival status at 28 d after admission. A mortality risk prediction model was constructed and nomogram was drawn. The value of the mortality risk prediction model, PEWS, PCIS and PRISM in predicting the risk of death was assessed and compared using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC).Results:Among the 178 critically ill children, 11 cases were excluded due to severe data deficiencies and hospitalization not exceeding 24 h. A total of 167 children were included in the analysis, including 134 in the survival group and 33 in the death group. A mortality risk prediction model for children with severe bacterial infection was constructed using pupillary changes, state of consciousness, skin color, mechanical ventilation, total cholesterol and prothrombin time. ROC curve analysis showed that the AUCs of mortality risk prediction model was 0.888 ( P<0.05). The AUCs of PEWS, PCIS and PRISM Ⅲ in predicting death in children with severe bacterial infection were 0.769 ( P< 0.05), 0.575 ( P< 0.05) and 0.759 ( P< 0.05), respectively. Hosmer-Lemeshow goodness-of-fit test showed the best agreement between risk of death and PEWS predicted morbidity and mortality and actual morbidity and mortality (χ 2 = 5.180, P = 0.738; χ 2 = 4.939, P = 0.764), and the PCIS and PRISM Ⅲ predicted mortality rates fitted reasonably well with actual mortality rates (χ 2= 9.110, P= 0333; χ 2 = 8.943, P= 0.347). Conclusions:The mortality risk prediction model for predicting the death risk has better prognostic value than PEWS, PCIS and PRISM Ⅲ for children with severe bacterial infection.

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OBJECTIVES: To describe the association of biomarkers with serious bacterial infection (SBI; urinary tract infection [UTI], bacteremia and/or bacterial meningitis) in hypothermic infants presenting to the emergency department (ED). METHODS: We performed a cross sectional study in four academic pediatric EDs from January 2015 through December 2019, including infants ≤90 days old presenting with a rectal temperature of ≤36.4 °C. We constructed receiver operating characteristic (ROC) curves to evaluate the accuracy of blood biomarkers including white blood cell count (WBC), absolute neutrophil count (ANC) and platelets for identifying SBI, with exploratory analyses evaluating procalcitonin and band counts. RESULTS: Among 850 included infants (53.5% males; median days of age 13 [IQR 5-58 days]), SBI were found in 55 (6.5%). For infants with SBI, the area under the curve (AUC; 95% confidence interval) for WBC was 0.70 (0.61-0.78) with sensitivity 0.64 (0.50-0.74) and specificity 0.77 (0.74-0.80). The AUC for ANC was 0.77 (0.70-0.84) with sensitivity 0.69 (0.55-0.81) and specificity 0.77 (0.74-0.8). For platelets, the AUC was 0.6 (0.52-0.67) with sensitivity 0.73 (0.59-0.84) and specificity 0.5 (0.46-0.53). Both the WBC and ANC were minimally accurate for identifying hypothermic infants with SBI. When looking at the accuracy of these biomarkers for identifying invasive bacterial infection (IBI; bacteremia and/or bacterial meningitis), ANC again showed minimal accuracy with an AUC of 0.70 (0.55-0.85). CONCLUSIONS: Biomarkers commonly used as part of an infectious workup are generally poor at identifying SBI in hypothermic infants. Our findings from this cohort of hypothermic infants are similar to those reported from febrile infants, suggesting similarities in the bioresponse to infection between hypothermic and febrile infants. Additional research is required to improve risk stratification for hypothermic infants, and to better guide evaluation and management.

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