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BACKGROUND: Fever in children represents one of the most common causes of medical evaluation. Infants younger than 90 days of age are at higher risk of severe and invasive bacterial infections (SBI and IBI). However, clinical signs and symptoms of viral and bacterial infections in young infants are frequently similar, and several studies have shown that the risk of SBIs remains non-negligible even in the presence of a positive point-of-care viral test. Our study aims to evaluate whether the proportion of SBIs and IBIs in febrile infants younger than 90 days during the COVID-19 pandemic was higher than that in the pre-pandemic period, and to describe the proportion of SBIs and IBIs in infants with and without SARS-CoV-2 infection. METHODS: This was a retrospective single-center cohort study conducted at the Children's Hospital of the University of Padua in Italy, involving febrile young infants evaluated in the Pediatric Emergency Department (PED) and admitted to Pediatric Acute Care Unit (PACU) between March 2017 to December 2022. Infants admitted before the COVID-19 pandemic were compared to infants admitted during the pandemic period and SARS-CoV-2 positive patients to the negative ones. RESULTS: 442 febrile infants younger than 90 days were evaluated in Padua PED and admitted to the wards. The proportion of SBIs and IBIS did not significantly change over the study periods, ranging between 10.8% and 32.6% (p = 0.117) and between 0% and 7.6%, respectively (p = 0.367). The proportion of infants with a diagnosis of SBIs and IBIs was higher in the SARS-CoV-2 negative group (30.3% and 8.2%, respectively) compared to the positive group (8.5% and 2.8%, respectively) (p < 0.0001). The most common diagnosis in both groups was UTI, mainly caused by E. coli. A similar proportion of blood and urine cultures were performed, whereas lumbar puncture was more frequently performed in SARS-CoV-2 negative infants (40.2% vs 16.9%, p = 0.001). CONCLUSIONS: Although the risk of concomitant serious bacterial infection with SARS-CoV-2 is low, it remains non-negligible. Therefore, even in SARS-CoV-2-positive febrile infants, we suggest that the approach to screening for SBIs remains cautious.

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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 neutropenia is a common clinical presentation in children that can be associated with invasive bacterial infection (IBI). However, in otherwise healthy children and youth with fever and neutropenia, the risk for IBI is low, with most cases being caused by viral infections. Well-appearing, non-oncologic, and presumed immunocompetent children aged 6 months to 18 years experiencing a first episode of neutropenia, with no additional risk factors, typically do not require empiric antibiotics. However, a thorough assessment, including complete history and physical exam, is indicated, and a blood culture should be performed when the absolute neutrophil count is <0.5 × 109/L. Close follow-up, a repeat complete blood count, and strong anticipatory guidance are recommended.

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Background The incidence of severe bacterial infections (SBIs) in infants aged ≤90 days is thought to have decreased because of widespread vaccination programs. However, relevant epidemiological data in Japan are scarce. Materials and methods This observational, single-center study investigated the epidemiology of fever in infants aged ≤90 days. SBI was defined as the presence of meningitis, urinary tract infections (UTIs), or bacteremia. Invasive bacterial infection (IBI) was defined as the presence of meningitis, bacteremic UTI, or bacteremia. We determined the incidence of UTIs, bacteremia, meningitis, SBIs, and IBIs in the following three age groups: 0-28, 29-60, and 61-90 days. We subsequently calculated the relative incidence for the groups aged 29-60 and 61-90 days, using the group aged 0-28 days as the reference group.  Results Herein, 58, 124, and 166 infants were included in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. Of the total number of patients, 15.5%, 8.9%, and 16.9% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with SBI. The relative incidences were 1 for the 0-28 days group (reference group), 0.67 for the 29-60 days group (95% confidence interval [CI], 0.39-1.15), and 1.08 for the 61-90 days group (95% CI, 0.58-2.00). Of the total number of patients, 10.3%, 3.2%, and 0.6% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with IBI. Relative incidences were 1 (reference group), 0.50 (95% CI, 0.29-0.88), and 0.28 (95% CI, 0.19-0.41) for the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. All cases of IBI were caused by Group B streptococcus (GBS), except for two cases of bacteremia, which were caused by Haemophilus influenzae.  Conclusion The incidence of SBI was similar in the 0-28 days and 61-90 days age groups. However, the incidence of IBI decreased with increasing age. The incidence of UTIs was highest in the 61-90 days age group, and that of meningitis and bacteremia decreased with increasing age.

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BACKGROUND: Machine learning models have demonstrated superior performance in predicting invasive bacterial infection (IBI) in febrile infants compared to commonly used risk stratification criteria in recent studies. However, the black-box nature of these models can make them difficult to apply in clinical practice. In this study, we developed and validated an explainable deep learning model that can predict IBI in febrile infants ≤ 60 days of age visiting the emergency department. METHODS: We conducted a retrospective study of febrile infants aged ≤ 60 days who presented to the pediatric emergency department of a medical center in Taiwan between January 1, 2011 and December 31, 2019. Patients with uncertain test results and complex chronic health conditions were excluded. IBI was defined as the growth of a pathogen in the blood or cerebrospinal fluid. We used a deep neural network to develop a predictive model for IBI and compared its performance to the IBI score and step-by-step approach. The SHapley Additive Explanations (SHAP) technique was used to explain the model's predictions at different levels. RESULTS: Our study included 1847 patients, 53 (2.7%) of whom had IBI. The deep learning model performed similarly to the IBI score and step-by-step approach in terms of sensitivity and negative predictive value, but provided better specificity (54%), positive predictive value (5%), and area under the receiver-operating characteristic curve (0.87). SHapley Additive exPlanations identified five influential predictive variables (absolute neutrophil count, body temperature, heart rate, age, and C-reactive protein). CONCLUSION: We have developed an explainable deep learning model that can predict IBI in febrile infants aged 0-60 days. The model not only performs better than previous scoring systems, but also provides insight into how it arrives at its predictions through individual features and cases.

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Aim: We aimed to investigate the performance of procalcitonin (PCT) assay between 12 and 36 h after onset of fever (PCT H12-H36) to predict invasive bacterial infection (IBI) (ie, meningitis and/or bacteremia) in febrile neonates. Methods: We retrospectively included all febrile neonates hospitalized in the general pediatric department in a teaching hospital from January 2013 to December 2019. PCT assay ≤ 0.6 ng/ml was defined as negative. The primary outcome was to study the performance of PCT H12-H36 to predict IBI. Results: Out of 385 included neonates, IBI was ascertainable for 357 neonates (92.7%). We found 16 IBI: 3 meningitis and 13 bacteremia. Sensitivity and specificity of PCT H12-H36 in the identification of IBI were, respectively, 100% [95% CI 82.9-100%] and 71.8% [95% CI 66.8-76.6%], with positive and negative predictive values of 14.3% [95% CI 8.4-22.2%] and 100% [95% CI 98.8-100%] respectively. Of the 259 neonates who had a PCT assay within the first 12 h of fever (< H12) and a PCT assay after H12-H36, 8 had IBI. Two of these 8 neonates had a negative < H12 PCT but a positive H12-H36 PCT. Conclusions: PCT H12-H36 did not miss any IBI whereas < H12 PCT could missed IBI diagnoses. PCT H12-H36 might be included in clinical decision rule to help physicians to stop early antibiotics in febrile neonates.

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Background and Objectives: To determine the rate of serious-bacterial-infections (SBI) in young ex-premature infants with fever, and to develop a risk-stratification algorithm for these patients. Methods: A retrospective cohort study including all infants who presented to the pediatric emergency department (ED) of a tertiary-care university-hospital between 2010 and 2020 with fever (≥38°C), were born prematurely (<37-weeks), had post-conception age of <52-weeks, and had available blood, urine, or CSF cultures. The rates of SBI by age-of-birth and age-at-visit were calculated and compared to a cohort of matched full-term controls. Results: The study included a total of 290 ex-premature cases and 290 full-term controls. There were 11 cases (3.8%) with an invasive bacterial infection (IBI) of either bacteremia, meningitis or both and only six controls (2.1%) with IBI (p = 0.32). Over 28-days chronologic-age, there were 10 (3.6%) IBIs among cases and no IBIs among the controls (p = 0.02). There were eight (3%) cases and three (1%) controls with IBI who were well-appearing on physical examination (p = 0.19). All eight well-appearing ex-premature infants were under 60-days adjusted-age, seven of whom (88%) were also under 28-days adjusted-age. There were 28 (10.6%) cases and 34 (12%) controls with urinary tract infection (UTI) (p = 0.5). Among cases under 60-days adjusted-age, urinalysis was not reliable to exclude UTI (50% negative). Conclusions: Well-appearing ex-preterm infants have a significant risk for IBI until the adjusted age of 28-days and for UTI until the adjusted age of 60-days. Further studies are needed to evaluate the approach to fever in this unique population.

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Currently, urbanization is associated with an increase in air pollutants that contribute to invasive pathogen infections by altering the host's innate immunity and antimicrobial resistance capability. Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a gram-positive opportunistic pathogen that causes a wide range of diseases, especially in children and immunosuppressed individuals. Diesel exhaust particle (DEP), a significant constituent of particulate matter (PM), are considered a prominent risk factor for respiratory illness and circulatory diseases worldwide. Several clinical and epidemiological studies have identified a close association between PM and the prevalence of viral and bacterial infections. This study investigated the role of DEP exposure in increasing pulmonary and blood bacterial counts and mortality during GAS M1 strain infection in mice. Thus, we characterized the upregulation of reactive oxygen species production and disruption of tight junctions in the A549 lung epithelial cell line due to DEP exposure, leading to the upregulation of GAS adhesion and invasion. Furthermore, DEP exposure altered the leukocyte components of infiltrated cells in bronchoalveolar lavage fluid, as determined by Diff-Quik staining. The results highlighted the DEP-related macrophage dysfunction, neutrophil impairment, and imbalance in pro-inflammatory cytokine production via the toll-like receptor 4/mitogen-activated protein kinase signaling axis. Notably, the tolerance of the GAS biofilms toward potent antibiotics and bacterial resistance against environmental stresses was also significantly enhanced by DEP. This study aimed to provide a better understanding of the physiological and molecular interactions between exposure to invasive air pollutants and susceptibility to invasive GAS infections.

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BACKGROUND: Febrile neonates undergo lumbar puncture (LP), empiric antibiotic administration, and admission for increased risk of invasive bacterial infection (IBI), defined as bacteremia and meningitis. OBJECTIVE: Measure IBI prevalence in febrile neonates, and operating characteristics of Rochester Criteria (RC), Yale Observation Scale (YOS) score, and demographics as a low-risk screening tool. METHODS: Secondary analysis of healthy febrile infants < 60 days old presenting to any of 26 emergency departments in the Pediatric Emergency Care Applied Research Network between December 2008 and May 2013. Of 7334 infants, 1524 met our inclusion criteria of age ≤ 28 days. All had fevers and underwent evaluation for IBI. Receiver operator characteristic (ROC) curve and transparent decision tree analysis were used to determine the applicability of reassuring RC, YOS, and age parameters as an IBI low-risk screening tool. RESULTS: Of 1524 neonates, 2.9% had bacteremia and 1.5% had meningitis. After applying RC and YOS, 15 neonates were incorrectly identified as low risk for IBI (10 bacteremia, 4 meningitis, 1 bacteremia, and meningitis). Age ≤ 18 days was a statistically significant variable ROC (area under curve 0.63, p < 0.05). Incorporating age > 18 days as low-risk criteria with reassuring RC and YOS misclassified 7 IBI patients (6 bacteremia, 1 meningitis). CONCLUSION: Thirty percent of febrile neonates met low-risk criteria, age > 18 days, reassuring RC and YOS, and could avoid LP and empiric antibiotics. Our low-risk guidelines may improve patient safety and reduce health care costs by decreasing lab testing for cerebrospinal fluid, empiric antibiotic administration, and prolonged hospitalization. These results are hypothesis-generating and should be verified with a randomized prospective study.

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BACKGROUND: Thalassemic patients usually require regular blood transfusions; however, HSCT can provide a cure. Incidence of IBI in pediatric patients post-HSCT is still scant. OBJECTIVES: This study aimed to explore whether thalassemic patients had a different incidence of post-HSCT IBI compared with patients with other underlying diseases. Factors associated with IBI in the pediatric population undergoing HSCT were also investigated. METHODS: In this retrospective cohort study, clinical data of pediatric patients who underwent HSCT during the period from 2011 to 2016 were reviewed and analyzed. The primary outcome was incidence of IBI within 1-year post-HSCT. RESULTS: Of 123 patients, 53 were thalassemic. IBI was diagnosed in 23 patients within 1 year after HSCT (incidence: 19.5 episodes/1000 patients/month). The IBI incidence was lower in thalassemic patients than in patients with other underlying diseases (6.9 vs. 31.6 episodes/1000 patients/month). Having thalassemia as an underlying disease was the only factor associated with lower IBI in pediatric post-HSCT patients (hazard ratio: 0.245; 95% confidence interval, 0.080-0.748). In post-HSCT thalassemic patients, IBI mostly occurred within 100 days after HSCT, and most of these cases had catheter-related blood stream infection. The risk of IBI tended higher for haploidentical HSCT, but this difference was not statistically significantly different. CONCLUSION: The IBI incidence after HSCT was lower in thalassemic patients than in those with other underlying diseases. Catheter-related blood stream infection was the major IBI in these patients. IBI was not a major complication in thalassemic pediatric patients undergoing HSCT.

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Objective: To provide epidemiological data of infants < 90 days of age with suspected late-onset sepsis (LOS) and evaluate distinct immunological specificities. We hypothesized that previously healthy infants < 3 months of age with sepsis have a yet undefined immunological predisposition; e.g. differences in lymphocyte subsets including regulatory T cells. Methods: We performed an exploratory, single center study between January 1st, 2019 and June 1st, 2021. Routine diagnostics included conventional culture (blood, cerebrospinal fluid, urine), PCR and inflammatory markers in infants < 90 days of age with suspected sepsis. We additionally analyzed lymphocyte subsets and CD4+ CD25+ forkhead box protein (FoxP3)+ Tregs at admission for sepsis workup as compared to age-matched controls. Results: A convenience sample cohort of n= 51 infants with sepsis workup was enrolled. Invasive bacterial infection (IBI) was diagnosed in 25 (49.0%) patients including two infants with a rhinovirus co-infection and viral infection in 14 (27.5%) neonates. No infectious cause was found in 12 cases. Infants with suspected LOS displayed a decreased abundance of CD4+ FoxP3+ T cells as compared to controls, which was most pronounced in the subgroup of infants with IBI. We also noticed elevated HLA-DR-positive CD3+ cells in infants with LOS and a higher CD4/CD8-ratio in infants with viral infection as compared to healthy controls. Infants with viral infections had a higher number of natural killer cells as compared to infants with IBI. Conclusion: Our exploratory data support the concept of a potential immaturity state and failed immune tolerance development for young infants with LOS. Future large-scale studies are needed to elucidate pre-sepsis conditions and to target the microbiome-immunity interplay as a potential risk pattern.

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BACKGROUND: The aim of this study was to develop and evaluate a machine learning (ML) model to predict invasive bacterial infections (IBIs) in young febrile infants visiting the emergency department (ED). METHODS: This retrospective study was conducted in the EDs of three medical centers across Taiwan from 2011 to 2018. We included patients age in 0-60 days who were visiting the ED with clinical symptoms of fever. We developed three different ML algorithms, including logistic regression (LR), supportive vector machine (SVM), and extreme gradient boosting (XGboost), comparing their performance at predicting IBIs to a previous validated score system (IBI score). RESULTS: During the study period, 4211 patients were included, where 126 (3.1%) had IBI. A total of eight, five, and seven features were used in the LR, SVM, and XGboost through the feature selection process, respectively. The ML models can achieve a better AUROC value when predicting IBIs in young infants compared with the IBI score (LR: 0.85 vs. SVM: 0.84 vs. XGBoost: 0.85 vs. IBI score: 0.70, p-value < 0.001). Using a cost sensitive learning algorithm, all ML models showed better specificity in predicting IBIs at a 90% sensitivity level compared to an IBI score > 2 (LR: 0.59 vs. SVM: 0.60 vs. XGBoost: 0.57 vs. IBI score >2: 0.43, p-value < 0.001). CONCLUSIONS: All ML models developed in this study outperformed the traditional scoring system in stratifying low-risk febrile infants after the standardized sensitivity level.

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BACKGROUND: Young infants with a possible serious bacterial infection (SBI) are a very common presentation to emergency centres (ECs). It is often difficult to distinguish clinically between self-limiting viral infections and an SBI. Available evaluation algorithms to assist clinicians are mostly from high-income countries. Data to inform clinical practice in low- and middle-income countries are lacking. OBJECTIVES: To determine the period prevalence of SBI and invasive bacterial infection (IBI) and describe current practice in the assessment and management of young infants aged 21-90 days presenting with a possible SBI to a Paediatric Emergency centre (PEC) in Cape Town, South Africa. METHODS: A retrospective cross-sectional review of infants 21-90 days old presenting to the Tygerberg Hospital PED between 1 January 2016 and 31 May 2016. RESULTS: A total of 248 infants 21-90 days were included in the study. Sixty-two patients (25%, 95% CI 20-30) had an SBI and 13 (5.2%, 95% CI 3-8) had an IBI. One hundred and sixty-five infants had a possible SBI based on WHO IMCI criteria. The sensitivity of the WHO IMCI criteria in detecting SBI was 82.3% (95% CI 70.5-90.8) and the specificity 38.7% (95% CI 31.7-46.1). More than half (51.2%) of the infants received antibiotics within the 48 h prior to presentation, of which 33.5% included intramuscular injection of Ceftriaxone. Only 20 (8.0%) patients in this age group were discharged home after initial evaluation. A significant relationship was noted between fever and the risk of SBI (p-value 0.010) and IBI (p-value 0.009). There also appeared to be a significant relationship between nutritional status and IBI (p-value 0.013). CONCLUSION: Period prevalence of SBI and IBI was higher compared to that published in the literature. Validated evaluation algorithms to stratify risk of SBI are needed to assist clinicians in diagnosing and managing infants appropriately in low- and middle-income settings.

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INTRODUCTION: Fever is one of the most common reasons for consultation in the paediatric emergency department (ED). Because of fear of bacterial infection in parents and caregivers, clinicians often overprescribe laboratory tests and empirical antibiotic treatment. The aims of this study are to demonstrate that using a procalcitonin (PCT) rapid test-based prediction rule (1) would not be inferior to usual practice in terms of morbidity and mortality (non-inferiority objective) and (2) would result in a significant reduction in antibiotic use (superiority objective). METHODS AND ANALYSIS: This prospective multicentric cluster-randomised study aims to include 7245 febrile children aged 6 days to 3 years with a diagnosis of fever without source in 26 participating EDs in France and Switzerland during a 24-month period. During first period, all children will receive usual care. In a second period, a point-of-care PCT-based algorithm will be used in half of the clusters. The primary endpoints collected on day 15 after ED consultation will be a composite outcome of death or intensive care unit admission for any reason, disease-specific complications, diagnosis of bacterial infection after discharge from the ED for the non-inferiority objective and proportion of children with antibiotic treatment administered for the superiority objective. The endpoints will be compared between the two groups (experimental and control) by using a mixed logistic regression model adjusted on clustering of participants within centres and period within centres. DISCUSSION: If the algorithm is validated, a new strategy will be discussed with medical societies to safely manage fever in young children without the need for invasive procedures for microbiological testing or empirical antibiotics. ETHICS AND DISSEMINATION: This study was submitted to an independent ethics committee on 17 May 2018 (no. 2018-A00252-53). Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03607162; Pre-results.

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OBJECTIVE: To assess the prevalence of serious infections and mortality among infants ≤90 days of age presenting to the emergency department with hypothermia. STUDY DESIGN: We performed a cross-sectional cohort study of infants ≤90 days presenting to any of 40 EDs in the Pediatric Health Information Systems between January 1, 2009, and December 31, 2018. Infants with an International Classification of Diseases, ninth or tenth edition, admission/discharge diagnosis code of hypothermia were included. We determined the prevalence of serious bacterial infection (urinary tract infection, bacteremia, and/or bacterial meningitis), pneumonia, herpes simplex virus (HSV) infection, and emergency department/hospital mortality. RESULTS: We included 3565 infants (1633 male [50.9%] and 3225 ≤30 days of age [90.5%]). Most (65.0%) presented in the first week of life. There were 389 infants (10.8%) with a complex chronic condition. The prevalence of serious bacterial infection was 8.0% (n = 284), including 2.4% (n = 87) with urinary tract infection, 5.6% (n = 199) with bacteremia, and 0.3% (n = 11) with bacterial meningitis. There were 7 patients (0.2%) with neonatal HSV and 9 (0.3%) with pneumonia; 0.2% (n = 6) died. The presence of a complex chronic condition was associated with the presence of serious bacterial infection (P < .001) and was present in 3 of 6 patients who died. In a sensitivity analysis including patients with any diagnosis code of hypothermia (n = 8122), 14.9% had serious bacterial infection, 0.6% had HSV, and 3.3% had pneumonia; 2.0% died. CONCLUSIONS: Of infants with hypothermia ≤90 days of age, 8.3% had serious bacterial infections or HSV. Compared with literature from febrile infants, hypothermia is associated with a high mortality rate. Complex chronic conditions were particularly associated with poor outcomes. Additional research is required to risk stratify young infants with hypothermia.

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Invasive bacterial infection (IBI) is associated with significant morbidity and mortality among neonates. Clinical practice guidelines (CPGs) can expedite care and standardize management. We conducted a retrospective observational study of febrile infants aged 0 to 56 days to assess changes in clinical decision-making following febrile neonate CPG implementation in the pediatric emergency department of a tertiary care hospital. Data were reviewed pre- and post-CPG implementation, with 1-year separation for provider education. Fewer infants underwent laboratory testing (complete blood count, blood culture, urine culture, lumbar puncture), antibiotic administration, and hospital admission after implementation; the greatest decrease was observed among infants aged 29 to 56 days identified as not high risk for meningitis. Seven-day IBI readmission rate was 1% in both groups. Herpes simplex virus testing and treatment did not differ significantly between groups. These results suggest that CPGs can enable both standardized care and decreased intervention in this population with no change in 7-day readmission rates.

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BACKGROUND: The early recognition of invasive bacterial infections (IBI) in children can be difficult. Clinically it is often challenging to differentiate between the early stages of an IBI and a benign self-limiting viral infection. These challenges mandate a cautious approach resulting in the overuse of antimicrobial drugs with resultant antimicrobial resistance. Due to these challenges, there is growing research into the role of biomarkers for the early identification of children with IBI. Earlier and more accurate diagnoses may lead to improved clinical outcomes for children and reduced antimicrobial resistance. Mid-regional pro-adrenomedullin (MR-proADM) is a biomarker that has been shown to be elevated in patients with IBI. The aim of this systematic review is to determine the diagnostic accuracy of MR-proADM at identifying children with IBI. METHODS: To identify relevant studies we will search MEDLINE, Embase, Web of Science and Scopus from 1980 to the present day for all human clinical trials involving children that report the test accuracy of MR-proADM. We will include case-control studies, cohort studies and randomised control trials reported in any language. In addition, we will hand-search reference lists and grey literature including conference abstracts and web searches. Two reviewers will independently screen study titles and abstracts for eligibility followed by full-text assessment and data extraction including population, setting, timing and use of index test and reference standard used. Methodological quality will be assessed, by two authors, according to the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2), any discrepancies will be resolved by a third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. DISCUSSION: This review will report the normal ranges for MR-proADM in health and the diagnostic accuracy of MR-proADM at identifying children with IBI. The review will help to define where in the diagnostic pathway MR-proADM could be useful including potential as a point-of-care test for children at first presentation with IBI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018096295.

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We conducted a secondary analysis of a prospective study of infants ≤60 days of age who were febrile to assess the diagnostic accuracy of automated vs manual immature neutrophils for invasive bacterial infections. Although manual counts were superior compared with automated counts, bands had suboptimal accuracy overall and had significant variability in test characteristics based on methodology.

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BACKGROUND: The Surviving Sepsis Campaign (SSC) recommends that intravenous antimicrobials be administered within one hour to treat sepsis in both adult and pediatric patients. However, most studies on the timing of antibiotics have been based on adults so far. Therefore, the goal of this study was to clarify the clinical outcomes of the timing of antibiotics use in young infants diagnosed with invasive bacterial infections. METHODS: We conducted this retrospective, cohort study at a single tertiary medical center during the period of 2007-2013 and included young infants visiting the PED diagnosed with an invasive bacterial infection. Early antibiotics use is defined as broad-spectrum intravenous antibiotics given within one hour of a patient's triage at PED. In this study, we have analyzed the factors associated with early antibiotics use and measured such primary outcomes as mortality, ICU admission, ventilation support, and length of hospital stay. RESULTS: A total of 1231 visits of young infants with fever occurred during our study period, and we included 41 patients in our study; 29 of them were diagnosed with bacteremia and the remaining 12 with bacterial meningitis. Early antibiotics use was also associated with a shortened hospital stay (14 ± 8.5 vs. 24 ± 19.6; p = 0.043). However, no statistical differences were observed with regard to mortality, ICU admission, or ventilation support. CONCLUSION: Among young infants that visited the pediatric department with an invasive bacterial infection, early broad-spectrum antibiotics use was not associated with reduced mortality rate, ICU admission, or ventilator support. However, it may have advantages regarding hospital length of stay.

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AIM: Our aim was to determine the effectiveness and safety of a procalcitonin-guided protocol to decrease antibiotic use in infants with severe bronchiolitis. METHODS: This prospective, observational study was conducted at the Hospital Sant Joan de Déu from 2010 to 2017. Patients under the age of one were included if they were diagnosed with bronchiolitis, had a suspected bacterial infection and were admitted to the paediatric intensive care unit. A procalcitonin-guided protocol was established in 2014, and two cohorts were compared before and after implementation: 340 in 2010-2014 and 366 in 2015-2017. RESULTS: We recruited 706 patients (58.6% male) with a median age of 47 days and an interquartile range of 25.0-100.2. The rate for antibiotic use was 79.9%, and this differed before and after implementation (88.2% vs 72.1%, P = .003). Antibiotic stewardship and withdrawal decisions were higher after implementation (22.3% vs 36.4%, P = .005). The length of antibiotic treatment was also different between the two periods (8.65 ± 4.8 days vs 5.05 ± 3.18 days, P = .023). No adverse outcomes were observed due to the implementation of the protocol. CONCLUSION: The implementation of a procalcitonin-guided protocol seems to lead to a safe and general decrease in antibiotic use in paediatric patients with severe bronchiolitis.

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