Bacterial coinfection in young febrile infants with SARS-CoV-2 infection.

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.

Neurodevelopmental outcomes following possible serious bacterial infection in early infancy in Karachi, Pakistan: a prospective cohort study.

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.

Optimizing integration of community-based management of possible serious bacterial infection (PSBI) in young infants into primary healthcare systems in Ethiopia and Kenya: successes and challenges.

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.

Management of well-appearing febrile young infants aged ≤90 days.

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.

Heart rate and respiratory rate in predicting risk of serious bacterial infection in febrile children given antipyretics: prospective observational study.

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.

Implementation research to increase treatment coverage of possible serious bacterial infections in young infants when a referral is not feasible: lessons learnt.

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.

Biomarkers and their association with bacterial illnesses in hypothermic infants.

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.

The evolving relationship between COVID-19 and serious bacterial infection evaluation in febrile neonates.

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.

A simple clinical decision rule may help to rule out severe bacterial infection and spare antibiotics in febrile young children.

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.

Clinical Timing-Sequence Warning Models for Serious Bacterial Infections in Adults Based on Machine Learning: Retrospective Study.

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.

Cost modelling incorporating procalcitonin for the risk stratification of febrile infants ≤60 days old.

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.

Risk-stratification in febrile infants 29 to 60 days old: a cost-effectiveness analysis.

BACKGROUND: Multiple clinical prediction rules have been published to risk-stratify febrile infants ≤60 days of age for serious bacterial infections (SBI), which is present in 8-13% of infants. We evaluate the cost-effectiveness of strategies to identify infants with SBI in the emergency department. METHODS: We developed a Markov decision model to estimate outcomes in well-appearing, febrile term infants, using the following strategies: Boston, Rochester, Philadelphia, Modified Philadelphia, Pediatric Emergency Care Applied Research Network (PECARN), Step-by-Step, Aronson, and clinical suspicion. Infants were categorized as low risk or not low risk using each strategy. Simulated cohorts were followed for 1 year from a healthcare perspective. Our primary model focused on bacteremia, with secondary models for urinary tract infection and bacterial meningitis. One-way, structural, and probabilistic sensitivity analyses were performed. The main outcomes were SBI correctly diagnosed and incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: In the bacteremia model, the PECARN strategy was the least expensive strategy ($3671, 0.779 QALYs). The Boston strategy was the most cost-effective strategy and cost $9799/QALY gained. All other strategies were less effective and more costly. Despite low initial costs, clinical suspicion was among the most expensive and least effective strategies. Results were sensitive to the specificity of selected strategies. In probabilistic sensitivity analyses, the Boston strategy was most likely to be favored at a willingness-to-pay threshold of $100,000/QALY. In the urinary tract infection model, PECARN was preferred compared to other strategies and the Boston strategy was preferred in the bacterial meningitis model. CONCLUSIONS: The Boston clinical prediction rule offers an economically reasonable strategy compared to alternatives for identification of SBI.

Paediatric emergency departments should manage young febrile and afebrile infants the same if they have a fever before presenting.

AIM: Our aim was to evaluate the risk of bacterial meningitis, bacteremia, and urinary tract infection (UTI) in infants ≤60 days who presented to paediatric emergency departments (PEDs) after having fever at home. We also investigated any differences between infants who were afebrile or febrile on presentation. METHODS: This was a multicenter retrospective study of infants ≤60 days presented to four Swedish PEDs during 2014-2020 with reported fever at home. We used relative risks (RR) to compare the prevalence of UTI, bacteremia, and bacterial meningitis between the infants who were afebrile and the infants who were still febrile when they presented to the PED. RESULTS: The cohort comprised 1926 infants, and 702 (36%) were afebrile on presentation. The prevalence of UTI in the afebrile and febrile infants was 6.1% [95% confidence interval (CI) 4.5-8.2] versus 14.2% (95% CI 12.3-16.2), corresponding to an RR of 0.43 (95% CI 0.31-0.59). In infants ≤28 days, the RR for meningitis was 1.05 (95% CI 0.18-6.23) for afebrile versus febrile infants. Five times more febrile infants underwent a lumbar puncture. CONCLUSION: Infants who were afebrile on presentation underwent fewer lumbar punctures, but they had similar rates of bacterial meningitis to febrile infants. Different management approaches are not justified.

Management of bacterial infections in young infants in Ethiopia: Facility preparedness, health workers' knowledge and quality of care.

AIM: We assessed primary care facility preparedness, health workers' knowledge and their classification and treatment of possible serious bacterial infection and local bacterial infection in young infants aged 0-59 days. METHOD: A cross-sectional survey was conducted in four regions of Ethiopia, including 169 health posts with 276 health extension workers and 155 health centres with 175 staff. Registers of 1058 sick young infants were reviewed. RESULT: Antibiotics to treat possible serious bacterial infection were available in 71% of the health centres and 38% of the health posts. Nine of ten health extension workers and eight of ten health centre staff mentioned at least one sign of possible serious bacterial infection and local bacterial infection. Among the registered cases with signs of bacterial infections, the health extension workers classified 49% as having a possible serious bacterial infection and 88% as local bacterial infection. The health centre staff classified 25% as possible serious bacterial infections and 86% as local bacterial infections. One-fourth (26%) of possible serious bacterial infection received the recommended treatment at health posts and 35% at health centres. CONCLUSION: Many health posts lacked antibiotics. The classification and treatment of possible serious bacterial infection did not follow guidelines. The lack of medicines and poor adherence compromise the quality of care.

Potential and promising marker for serious bacterial infections in children: Delta neutrophil index.

AIM: This study aimed to evaluate the usefulness and accuracy of the delta neutrophil index (DNI), an index expressing the number of immature granulocytes as a proportion of the total, as an inflammatory marker in predicting serious bacterial infections (SBIs). METHODS: Paediatric patients admitted to our hospital with fever were divided into four groups: SBI, non-SBI, COVID-19 and control group. White blood cell count, absolute neutrophil count, C-reactive protein and the DNI were recorded, and their accuracy in predicting SBI was evaluated. RESULTS: Mean DNI was 4.96 ± 8.38 in the SBI group (150 patients), 0.67 ± 1.68 in the non-SBI group (397 patients), 0.29 ± 0.99 in the COVID-19 group (112 patients) and 0.14 ± 0.21 in the control group (102 patients). The DNI was significantly higher in the SBI group compared with the non-SBI (P < 0.001); the non-SBI group also had higher levels than the COVID-19 group (P = 0.005). One percent increase in the DNI increased the SBI rate 1.36 times (odds ratio 1.36 (95% confidence interval 1.23-1.49), P < 0.001). Based on the determined cut-off value (>2.5%), the DNI (odds ratio 6.27 (95% confidence interval 3.85-10.21), P < 0.001) significantly predicted SBIs with 90.4% specificity and 47.7% sensitivity. CONCLUSIONS: SBIs in childrenare associated with an increase in DNI levels. Compared to other biomarkers, the DNI had higher specificity in predicting SBIs. The DNI may also be usefulin differentiating bacterial and non-bacterial infections in individualclinical syndromes. Currently, there is no evidence that serum DNI aids indifferentiating COVID-19 and upper respiratory tract infection.

Multi-incident analysis of reviews of serious adverse clinical events in children with serious bacterial infection and/or sepsis in Queensland, Australia between 2012 and 2017.

AIM: To report on findings from a multi-incident analysis of reviews of serious paediatric adverse clinical events related to serious bacterial infection and/or sepsis (hereafter referred to as sepsis for brevity) in Queensland, Australia, between 2012 and 2017. METHODS: The Queensland Paediatric Quality Council reviewed documentation from reviews of serious adverse events occurring in children (<18 years) with a diagnosis of sepsis at Queensland public hospitals between 2012 and 2017, including clinical details, coronial reports, autopsy reports and root cause analysis documents. A multi-incident tool was designed and used by an expert panel to identify patient and facility demographics, contributing factors, and human and system factors associated with paediatric serious adverse events. RESULTS: There were 28 serious adverse clinical events reported related to paediatric sepsis, characterised by a high proportion of deaths (23) and a predominance of children aged under 4 years. Approximately half of all facilities were classified as rural and remote health services. Contributing factors included difficulty in recognising and responding to the deteriorating patient, inadequate management/treatment, diagnostic error (mainly diagnostic delay) and escalation delay/failure. Major system factors included communication issues, incorrect use of the early warning tool, inadequate coordination of care planning, policy/protocol/guideline failures and workforce problems. CONCLUSION: Multi-incident analysis is a useful tool for identifying themes that recur in similar events and presents opportunities for system-wide improvement. Common themes and contributing factors were identified which may provide possibilities for earlier identification and intervention in childhood serious bacterial infection and/or sepsis.

Using the Implementation Research Logic Model to design and implement community-based management of possible serious bacterial infection during COVID-19 pandemic in Ethiopia.

BACKGROUND: Community-based treatment of possible serious bacterial infection (PSBI) in young infants, when referral to a hospital is not possible, can result in high treatment coverage and low case fatality. However, in Ethiopia, the coverage of PSBI treatment remains low, worsened by COVID-19. To understand the challenges of delivery of PSBI treatment and design and test adaptative strategies to mitigate the impact of COVID-19 on neonatal mortality, we did implementation research (IR) employing Implementation Research Logic Model (IRLM). In this paper, we describe IRLM application experiences in designing, implementing, and evaluating strategies to improve community-based treatment of PSBI during the COVID-19 pandemic in Ethiopia. METHODS: This IR was conducted between November 2020-April 2022 at Dembecha and Lume woredas of Amhara and Oromia regions, respectively. We employed narrative reviews, formative assessment and facilitated stakeholder engagement to develop the PSBI treatment IRLM to identify barriers, understand the conceptual linkages among determinants, choose implementation strategies, elicit mechanisms, and link to implementation outcomes. In addition, we used the IRLM to structure the capture of emerging implementation challenges and resulting strategy adaptations throughout implementation. RESULTS: This IR identified COVID-19 and multiple pre-existing contextual factors. We designed and implemented implementation strategies to address these challenges. These adaptive strategies were implemented with sufficient strength to maintain the delivery of PSBI services and improve mothers' care-seeking behavior for their sick young infants. The IRLM offers us a clear process and path to prioritize implementation challenges, choose strategies informed by mechanisms of action, and where the adaptive implementation of community-based management of PSBI would lead to high-implementation fidelity and change in mother behavior to seek care for their sick young infants. The IRLM was also an effective tool for stakeholder engagement, easily explained and used to structure discussion and decision-making during co-design meetings. CONCLUSIONS: The use of the IRLM helps us to specify the conceptual links between the implementation challenges, strategies, mechanisms of action, and outcomes to explore the complex community-based management of PSBI during complex contexts to improve high-fidelity implementation and integration of PSBI treatment in the primary healthcare delivery systems through active engagement of stakeholders.

Comparison of Clinical and Epidemiologic Characteristics of Young Febrile Infants with and without Severe Acute Respiratory Syndrome Coronavirus-2 Infection.

OBJECTIVE: To determine features that distinguish febrile young infants with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: Retrospective single-center study included febrile infants <57 days of age evaluated in the emergency department of Cohen Children's Medical Center of Northwell Health, New Hyde Park, New York, from March 1 to April 30 of 2018, 2019, and 2020. Sociodemographic and clinical features were compared between those seen during the 2020 coronavirus disease-2019 pandemic and previous years, as well as between infants with SARS-CoV-2 infection and infants without SARS-CoV-2 infection (SARS-CoV-2 negative or evaluated during 2018 and 2019). RESULTS: In all, 124 febrile infants <57 days of age were identified; 38 during the 2-month study period in 2018, 33 in 2019, and 53 in 2020. During 2020, fewer febrile infants had a serious bacterial infection or a positive respiratory viral panel than in prior years (6% vs 21% [P = .02]; 15% vs 53% [P < .001], respectively). SARS-CoV-2 was the most frequent pathogen detected in 2020; of 30 infants tested, 20 tested positive. Infants with SARS-CoV-2 were more likely to identify as Hispanic (P = .004), have public insurance or be uninsured (P = .01), exhibited lethargy (P = .02), had feeding difficulties (P = .002), and had lower white blood cell (P = .001), neutrophil (P < .001), and lymphocyte counts (P = .005) than the 81 infants without SARS-CoV-2 infection. None of the infants with SARS-CoV-2 had concurrent serious bacterial infection or detection of another virus. Overall, disease in infants with SARS-CoV-2 was mild. CONCLUSIONS: During the peak of the pandemic, SARS-CoV-2 was the predominant pathogen among febrile infants. Socioeconomic, historical, and laboratory features differed significantly between infants infected or not infected with SARS-CoV-2. None of the 20 infants with SARS-CoV-2 infection had an identified coviral or serious bacterial infection.

Shivering has little diagnostic value in diagnosing serious bacterial infection in children: a systematic review and meta-analysis.

Early diagnosis of serious bacterial infections (SBI) is important for improving outcome of morbidity and mortality in children. A systematic review was conducted to examine if shivering had any value in diagnosing serious bacterial infection. We split our population (0-18 years old) into two categories depending on the presence of a known malignancy. The databases of Medline, Embase, Cinahl, and Web of Science were searched from inception until July 2019. The quality was assessed with the QUADAS-2 tool. Two by two tables were created, extracting the number of true positive (TP), true negative (TN), false positive (FP), and false negative (FN) regarding shivering and SBI, by 2 authors independently. Sensitivity, specificity, likelihood ratios, and their 95% confidence intervals were calculated using the MetaDATA Shiny app. In a population with known malignancy, we found a +LR of 3.47 (95% CI 2.58-4.36) for a serious bacterial infection when shivering was present, implying an increase of 25-30% possibility for a serious bacterial infection. In children without malignancy, diagnostic accuracy of shivering was poor.Conclusion: Shivering is of limited use to diagnose serious bacterial infection in children without malignancy. Nevertheless, in children with known malignancy, it can be useful as an alarm signal. What is Known: • In the NICE guidelines for febrile illness in children, "shivering" is considered as an intermediate risk factor ("amber" sign) for a serious illness. • A systematic literature search conducted in 2007 investigating the correlation between shivering in a febrile child and the presence of a serious bacterial infection could include only one study. What is New: • Based on the results of this systematic review, shivering has little diagnostic value in children without malignancy but can be useful as an alarm sign of serious bacterial infection in children with known malignancy. • In case of absence of shivering, serious bacterial infection cannot be ruled out.

Fever response to ibuprofen in viral and bacterial childhood infections.

OBJECTIVE: to compare the antipyretic effects of ibuprofen in febrile children with serious bacterial infections (SBI), and children with a presumed viral infection. METHODS: A prospective cross- sectional study was conducted in a pediatric Emergency department between October 2018 and March 2020 for children aged 3 months to 4 years with a rectal temperature ≥ 38.5 °C. Patients received 10 mg/kg of ibuprofen oral suspension. Rectal temperature was measured 60 and 120 min after administration. Laboratory and imaging evaluations were performed for each study participant in order to identify serious bacterial infection. RESULTS: Ninety patients were included, of which 18 were diagnosed with serious bacterial infections. There was no significant difference in age, fever at presentation and duration of fever between the groups. No significant difference was noted in body temperature reduction at 60 and 120 min after ibuprofen administration (1.09 ± 0.75 °C vs 0.89 ± 0.58 °C, mean difference -0.12 °C, 95% CI -0.54-0.15 °C; 1.85 ± 0.53 °C vs 1.78 ± 0.83 °C, mean difference - 0.07 °C, 95% CI -0.49-0.36 °C, in the SBI and non-SBI groups respectively). CONCLUSION: Fever response to Ibuprofen administration is not indicative of serious bacterial infections in children under 4 years of age. Larger prospective studies are required to define whether the lack of response to Ibuprofen has any impact on the management of febrile children.