Unexpected severe malaria in a postoperative patient, New York, USA.

Severe malaria is not routinely considered when evaluating a febrile patient in the postoperative setting. Common bacterial infections, along with adverse drug reactions, are the usual differential concerns. We present a case of severe malaria emerging unexpectedly eight days after routine craniotomy.

Protocol for the diagnostic performance of C reactive protein, procalcitonin and interleukin-6 for serious bacterial infections among children ≤36 months old presenting with fever without source: a systematic review and meta-analysis.

INTRODUCTION: The management of fever without source in children ≤36 months old remains a diagnostic challenge as the underlying aetiologies can vary from self-limiting viral infections to serious bacterial infections (SBIs). Biomarkers such as C reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) have varying thresholds in the prediction of SBIs due to differences in SBI definitions, SBI prevalence, patient characteristics and timing of presentation. This protocol describes a systematic review and meta-analysis that aims to determine the thresholds at which CRP, PCT and IL-6 can perform optimally in distinguishing the presence of SBIs in children ≤36 months old, as well as to determine their performances in early detection of bacterial infections within 48 hours of fever onset. METHODS AND ANALYSIS: We will systematically search electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane CENTRAL, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Science Citation Index from 1 July 2023 to 31 July 2023. We will include studies that report the diagnostic accuracy of CRP, PCT and IL-6 in detecting SBIs in children aged ≤36 months presenting with fever without apparent source. Randomised controlled trials (RCTs) and non-randomised studies including non-RCTs and controlled before-and-after studies will be included. A meta-analysis will be performed and diagnostic performances of these biomarkers will be reported. ETHICS AND DISSEMINATION: The results of this study will provide guidance on clinical decision-making in young children presenting with fever without source. Ethics approval will not be required for this study. The authors aim to publish the findings in a peer-reviewed journal as well as present at international conferences. PROSPERO REGISTRATION NUMBER: CRD42023439093.

Estimated C-reactive protein (CRP) velocity for rapidly distinguishing bacterial from other etiologies in children presenting to emergency department with remarkably elevated CRP levels.

The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults. This study aims to investigate the association between eCRPv and bacterial etiologies among pediatric patients with very elevated CRP levels. We conducted a retrospective analysis of patients under 18 years of age who had been admitted to our Pediatric Emergency Department from 2018 to 2020 with a fever and CRP levels ≥ 150 mg/L. Bacterial and non-bacterial etiologies were determined from hospital discharge diagnoses, which were monitored independently by three physicians from the research team. The records of 495 suitable patients (51.2% males, median age 3.2 years) were retrieved of whom 444 (89.7%) were eventually diagnosed with bacterial infections. The mean CRP levels were significantly higher for bacterial etiologies compared with other causes (209.2 ± 59.8 mg/L vs. 185.6 ± 35.8 mg/L, respectively, p < .001), while the mean eCRPv values did not differ significantly (p = .15). In a time course analysis, we found that specifically in patients presenting ≥ 72 h after symptom onset, only a eCRPv1 level > 1.08 mg/L/h was an independent predictor of bacterial infection (aOR = 5.5 [95% CI 1.7-17.8], p = .004).   Conclusion: Pediatric patients with very high CRP levels and fever mostly have bacterial infections. eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset, warranting further prospective investigations into CRP kinetics in pediatric patients. What is Known: • The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. • Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults, but data on CRP kinetics in pediatric patients is sparse. What is New: • eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset in pediatric patients with remarkably elevated CRP levels.

Monitoring the efficacy of antibiotic therapy in febrile pediatric oncology patients with bacteremia using infrared spectroscopy of white blood cells-based machine learning.

Bacteremia refers to the presence of bacteria in the bloodstream, which can lead to a serious and potentially life-threatening condition. In oncology patients, individuals undergoing cancer treatment have a higher risk of developing bacteremia due to a weakened immune system resulting from the disease itself or the treatments they receive. Prompt and accurate detection of bacterial infections and monitoring the effectiveness of antibiotic therapy are essential for enhancing patient outcomes and preventing the development and dissemination of multidrug-resistant bacteria. Traditional methods of infection monitoring, such as blood cultures and clinical observations, are time-consuming, labor-intensive, and often subject to limitations. This manuscript presents an innovative application of infrared spectroscopy of leucocytes of pediatric oncology patients with bacteremia combined with machine learning to diagnose the etiology of infection as bacterial and simultaneously monitor the efficacy of the antibiotic therapy in febrile pediatric oncology patients with bacteremia infections. Through the implementation of effective monitoring, it becomes possible to promptly identify any indications of treatment failure. This, in turn, indirectly serves to limit the progression of antibiotic resistance. The logistic regression (LR) classifier was able to differentiate the samples as bacterial or control within an hour, after receiving the blood samples with a success rate of over 95 %. Additionally, initial findings indicate that employing infrared spectroscopy of white blood cells (WBCs) along with machine learning is viable for monitoring the success of antibiotic therapy. Our follow up results demonstrate an accuracy of 87.5 % in assessing the effectiveness of the antibiotic treatment.

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.

Diagnosis of urinary tract infection in infants under 3 months with fever without a source: reliability of urinalysis and urine culture.

BACKGROUND: Urinary tract infection (UTI) is infants' most common serious bacterial infection. This study aimed to investigate the reliability of urianalysis (UA) to predict UTI, to specify the colony forming units (CFU)/ml threshold for diagnosis, and to identify variables that help suspect bacteremia in infants under 3 months with UTI. METHODS: We reviewed clinical records of children under 3 months hospitalized for a fever without source and recorded age, sex, days of fever pre-consultation, temperature and severity at admission, discharge diagnoses, laboratory tests, and treatments. According to the discharge diagnosis, we divided them into UTIs (-) and (+) with or without bacteremia. RESULTS: A total of 467 infants were admitted: 334 with UTI and 133 without UTI. In UTIs (+), the pyuria had a sensitivity of 95.8% and bacteria (+) 88.3%; specificity was high, especially for nitrites (96.2%) and bacteria (+) (92.5%). Positive predictive value (PPV) for nitrites was 95.9%, for bacteria 96.7%, and oyuria 92.5%. Escherichia coli was present in 83.8% of urine and 87% of blood cultures. UTIs with bacteremia had inflammatory urinalysis, urine culture > 100,000 CFU/ml, and higher percentage of C reactive protein (CRP) > 50 mg (p= 0.002); 94.6% of the urine culture had > 50,000 CFU. CONCLUSIONS: The pyuria and bacteria (+) in urine obtained by catheterization predict UTI. The cut-off point for diagnosis was ≥ 50,000 CFU/ml. No variables to suspect bacteremia were identified in this study.

INTRODUCCIÓN: La infección del tracto urinario (ITU) es una infección bacteriana grave frecuente en lactantes. El objetivo de este trabajo fue investigar la fiabilidad del análisis de orina (AO) para predecirla, precisar el umbral de unidades formadoras de colonias (UFC)/ml para el diagnóstico y buscar variables que ayuden a sospechar de bacteriemia en lactantes menores de 3 meses con ITU. MÉTODOS: Se revisaron fichas clínicas de lactantes menores de 3 meses hospitalizados por fiebre sin foco evidente, registrando edad, sexo, días de fiebre preconsulta, temperatura y gravedad al ingreso, diagnósticos de egreso, exámenes de laboratorio y tratamientos. Según diagnóstico de egreso, se separaron en ITU (-) y (+), con o sin bacteriemia. RESULTADOS: Ingresaron 467 lactantes: 334 con ITU y 133 sin ITU. En ITU (+), la sensibilidad de la piuria fue de 95.8% y bacterias (+) 88.3%; la especificidad fue alta para nitritos (96.2%) y bacterias (+) (92.5%). El valor predictivo positivo (VPP) fue de 95.9% para nitritos, 96.7% para bacterias y 92.5% para piuria. Escherichia coli se encontró en el 83.8% de los urocultivos (UC) (+) y en el 87% de los hemocultivos (+). Las ITU con bacteriemia presentaron elementos inflamatorios, UC con ≥ 100,000 UFC/ml y mayor porcentaje de proteína C reactiva (PCR) > 50 mg/l (p= 0.002); el 94.6% de los UC (+) tuvo ≥ 50,000 UFC/ml. CONCLUSIONES: La piuria y bacterias (+) en el AO son excelentes para pronosticar ITU en orina obtenida con sonda vesical y el punto de corte para el diagnóstico debe ser ≥ 50,000 UFC/ml. No encontramos señales que ayudaran a sospechar ITU con bacteriemia.

External validation of a multivariable prediction model for identification of pneumonia and other serious bacterial infections in febrile immunocompromised children.

OBJECTIVE: To externally validate and update the Feverkids tool clinical prediction model for differentiating bacterial pneumonia and other serious bacterial infections (SBIs) from non-SBI causes of fever in immunocompromised children. DESIGN: International, multicentre, prospective observational study embedded in PErsonalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union (PERFORM). SETTING: Fifteen teaching hospitals in nine European countries. PARTICIPANTS: Febrile immunocompromised children aged 0-18 years. METHODS: The Feverkids clinical prediction model predicted the probability of bacterial pneumonia, other SBI or no SBI. Model discrimination, calibration and diagnostic performance at different risk thresholds were assessed. The model was then re-fitted and updated. RESULTS: Of 558 episodes, 21 had bacterial pneumonia, 104 other SBI and 433 no SBI. Discrimination was 0.83 (95% CI 0.71 to 0.90) for bacterial pneumonia, with moderate calibration and 0.67 (0.61 to 0.72) for other SBIs, with poor calibration. After model re-fitting, discrimination improved to 0.88 (0.79 to 0.96) and 0.71 (0.65 to 0.76) and calibration improved. Predicted risk <1% ruled out bacterial pneumonia with sensitivity 0.95 (0.86 to 1.00) and negative likelihood ratio (LR) 0.09 (0.00 to 0.32). Predicted risk >10% ruled in bacterial pneumonia with specificity 0.91 (0.88 to 0.94) and positive LR 6.51 (3.71 to 10.3). Predicted risk <10% ruled out other SBIs with sensitivity 0.92 (0.87 to 0.97) and negative LR 0.32 (0.13 to 0.57). Predicted risk >30% ruled in other SBIs with specificity 0.89 (0.86 to 0.92) and positive LR 2.86 (1.91 to 4.25). CONCLUSION: Discrimination and calibration were good for bacterial pneumonia but poorer for other SBIs. The rule-out thresholds have the potential to reduce unnecessary investigations and antibiotics in this high-risk group.

[Neoehrlichiosis has entered the Stockholm region]. / Ovanlig fästingsjukdom har gjort sitt intåg i Stockholmsregionen.

The number of cases diagnosed with neoehrlichiosis in Stockholm has increased over the last years. PCR analysis is needed for the detection of the intracellular bacterium Neoehrlichia mikurensis. The real number of cases in the area is unknown since the specific PCR for N mikurensis is not routinely included in the workup for unknown fever in Stockholm. By describing three cases, we want to increase the awareness of neoehrlichiosis among clinicians. Symptoms of prolonged fever, myalgia and thrombosis among immunocompromised patients should raise the suspicion of neoehrlichiosis and the specific PCR analysis should be performed. The diagnosed patients were all treated with doxycycline; the fever disappeared within a few days, and clinical improvement was observed. After treatment no relapses were noticed, despite immunological deficiencies in the patients.

CA FIRST (California Febrile Infant Risk Stratification Tool) Algorithm Development in a Learning Health System.

Introduction There is considerable variation in the approach to infants presenting to the emergency department (ED) with fever. The authors' primary aim was to develop a robust set of algorithms using community ED data to inform modifications of broader clinical guidance. Methods The authors report the development of California Febrile Infant Risk Stratification Tool (CA FIRST) using key components of the Roseville Protocol (ROS) and American Academy of Pediatrics (AAP) Clinical Practice Guideline (CPG). Expanded guidance was derived using a retrospective analysis of a cohort of 3527 febrile infants aged 7-90 days presenting to any Kaiser Permanente Northern California ED between 2010 and 2019 who underwent a core febrile infant evaluation. Results Melding ROS and AAP CPG algorithms in infants 7-60 days old, CA FIRST Algorithms had comparable performance characteristics to ROS and AAP CPG. CA FIRST enhancements included guidance on febrile infants 61-90 days old, high-risk infants, infants with bronchiolitis, and infants who received immunizations within the prior 48 hours. This retrospective analysis revealed that of 235 febrile infants 22-90 days old with respiratory syncytial virus and 221 who had fever in the 48 hours following vaccination, there were no cases of invasive bacterial infection. Discussion CA FIRST is a set of 13 algorithms providing a thoughtful and flexible approach to the febrile infant while minimizing unnecessary interventions. Conclusions CA FIRST Algorithms empower clinicians to manage most febrile infants. Algorithms are being modified as new data become available, imparting useful and ever-current educational information within a learning health care system.

Bacterial Infections and Clinical Outcomes Among Febrile Infants up to 90 Days Old With SARS-CoV-2 Infection: A Multicenter Cohort Study.

We present a large, multicenter, cohort study that aimed to assess bacterial infection rates among febrile infants up to 90 days old presenting to the pediatric emergency department with severe acute respiratory syndrome coronavirus 2 infection during 2021-2022 throughout successive variant waves. Overall, 417 febrile infants were included. Twenty-six infants (6.2%) had bacterial infections. All bacterial infections consisted of urinary tract infections, and there were no invasive bacterial infections. There was no mortality.

A Novel Combination of Host Protein Biomarkers to Distinguish Bacterial From Viral Infections in Febrile Children in Emergency Care.

BACKGROUND: Distinguishing bacterial and viral infections based on clinical symptoms in febrile children attending the emergency department (ED) is challenging. The aim of this study is to determine a novel combination of host protein biomarkers and to assess its performance in distinguishing between bacterial and viral infection in febrile children attending EDs. METHODS: A literature search was performed to identify blood protein biomarkers able to distinguish bacterial and viral infections (May 2015-May 2019). We selected 7 protein biomarkers: Procalcitonin, TNF-related apoptosis-inducing ligand (TRAIL), interleukin (IL)-4, IL-6, Interferon gamma-induced protein-10 (CXCL-10), interferon-gamma and lipocalin 2 (LCN2). These were measured in blood plasma using a bead-based immunoassay in children with a confirmed bacterial or viral infection attending EDs in the Netherlands. We used generalized linear modeling to classify bacterial and viral infections and applied a previously developed feature selection algorithm to select the optimal combination of proteins. We performed a subgroup analysis of this protein signature in patients with C-reactive protein <60 mg/L, representing a clinically challenging diagnostic group. RESULTS: In total 102 children were included (N = 67 bacterial; N = 35 viral). Individual performance of the 7 biomarkers in classifying bacterial versus viral infections ranged from 60.8%-74.5% area under the receiver operator curve (AUC). TRAIL, LCN2 and IL-6 were identified as the best 3-protein signature with an AUC of 86% (95% CI: 71.3%-100%). In 57 patients with C-reactive protein levels <60 mg/L, the 3-protein signature had an AUC of 85.1% (95% CI: 75.3%-94.9%). CONCLUSION: We demonstrate a promising novel combination of 3 host protein biomarkers; TRAIL, LCN2 and IL-6, which performs well in classifying bacterial and viral infections in febrile children in emergency care.

Invasive bacterial infection in children with fever and petechial rash in the emergency department: a national prospective observational study.

OBJECTIVE: To determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae. DESIGN: A prospective, observational, multicentre study was conducted in 18 hospitals between November 2017 and October 2019. PATIENTS: A total of 688 patients were recruited. MAIN OUTCOME MEASURES: The primary outcome was the presence of IBI. Clinical features and laboratory test results were described and related to the presence of IBI. RESULTS: Ten IBIs were found (1.5%), comprising eight cases of meningococcal disease and two of occult pneumococcal bacteraemia. Median age was 26.2 months (IQR 15.3-51.2). Blood samples were obtained from 575 patients (83.3%). Patients with an IBI had a shorter time from fever to ED visit (13.5 hours vs 24 hours) and between fever and rash onset (3.5 hours vs 24 hours). Values for absolute leucocyte count, total neutrophil count, C reactive protein and procalcitonin were significantly higher in patients with an IBI. Significantly fewer patients with a favourable clinical status while in the observation unit were found to have an IBI (2/408 patients, 0.5%) than when clinical status was unfavourable (3/18, 16.7%). CONCLUSIONS: The incidence of IBI among children with fever and petechial rash is lower than previously reported (1.5%). The time from fever to ED visit and to rash onset was shorter in patients with an IBI. Patients with a favourable clinical course during observation in the ED are at lower risk of IBI.

Subcutaneous Microabscesses and Myositis as Part of Immune Reconstitution Inflammatory Syndrome due to Chronic Disseminated Candidiasis in a Child With Acute Lymphoblastic Leukemia.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) occurs when there is immune recovery after a prolonged period of leucopenia as a response to an underlying latent or chronic infection due to a proinflammatory cascade. It can occur in a child on chemotherapy for acute lymphoblastic leukemia (ALL) with underlying chronic disseminated candidiasis (CDC). OBSERVATION: We present a 7-year-old girl with pre-B ALL on chemotherapy who had prolonged febrile neutropenia and CDC with microabscesses in the liver, spleen, and kidney and a prolonged intensive care unit stay. Upon neutrophil recovery, she continued to have high-grade fever (blood and urine cultures negative). She also presented severe myositis of bilateral thigh muscles and developed unusual granulomas in the subcutaneous region of the lower back and right thigh. Although IRIS was suspected, she could not be initiated on steroids due to right upper lobe collapse consolidation due to multidrug-resistant Acinetobacter baumanni, which was treated with sensitive antibiotics. Treatment with steroids resolved her fever and normalized inflammatory markers. She is currently well on maintenance chemotherapy. CONCLUSIONS: IRIS can complicate the treatment of ALL in children. Diagnosing it while having a concurrent bacterial infection is challenging. Rarely CDC can present with subcutaneous granulomas. Treatment with steroids at the right time is very crucial.

Clinical and microbiological profiles in post-chemotherapy neutropenic fever in hematological malignancy: exploration of clinical phenotype patterns by two-step cluster analysis.

BACKGROUND: Epidemiology of infectious diseases causing febrile illness varies geographically with human attributes. Periodic institutional surveillance of clinical and microbiological profiles in adding data to updating trends, modulating pharmatherapeutics, signifying possible excessive treatments and risk of drug resistance in post-chemotherapy neutropenic fever (NF) in hematological malignancy (HM) is limited. We aimed to review institutional clinical and microbiological data and explore clinical phenotype pattern groups among data. METHODS: Available data from 372 NF episodes were included. Demographics, types of malignancies, laboratory data, antimicrobial treatments and febrile-related outcome data such as predominant pathogens and microbiological diagnosed infections (MDIs) were collected. Descriptive statistics, two-step cluster analysis and non-parametric tests were employed. RESULTS: The occurrences of microbiological diagnosed bacterial infections (MDBIs; 20.2%) and microbiological diagnosed fungal infections (MDFIs; 19.9%) were almost equal. Gram-negative pathogens (11.8%) were comparable with gram-positive pathogens (9.9%), with gram-negative being slightly predominant. Death rate was 7.5%. Two-step cluster analysis yielded four distinct clinical phenotype pattern (cluster) groups: cluster 1 'lymphomas without MDIs', cluster 2 'acute leukemias MDBIs', cluster 3 'acute leukemias MDFIs' and cluster 4 'acute leukemias without MDIs'. Considerable NF events with antibiotic prophylaxis being not identified as MDI might have cases in low-risk with non-infectious reasons causing febrile reactions that might possibly not require prophylaxis. CONCLUSIONS: Regular institutional surveillance with active parameter assessments to signify risk levels in the post-chemotherapy stage, even prior to the onset of fever, might be an evidence-based strategy in the management of NF in HM.

Explainable deep learning model to predict invasive bacterial infection in febrile young infants: A retrospective study.

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.

Chronic Disseminated Candidiasis in Children and the Role of Corticosteroids Therapy.

BACKGROUND: Little is known about chronic disseminated candidiasis (CDC) in children. This study was done to describe the epidemiology, risk factors and outcome of CDC in children managed at Sultan Qaboos University Hospital (SQUH), Oman, and to describe the role of corticosteroids in the management of immune reconstitution inflammatory syndrome (IRIS) complicating CDC. METHODS: We retrospectively reported demographic, clinical and laboratory data of all children managed in our center for CDC between January 2013 and December 2021. In addition, we discuss the available literature on the role of corticosteroids for management of CDC-related IRIS in children since 2005. RESULTS: Between January 2013 and December 2021, 36 immunocompromised children were diagnosed with invasive fungal infection at our center, of whom 6 had CDC (all with acute leukemia). Their median age was 5.75 years. Prolonged fever despite broad-spectrum antibiotics (6/6) followed by skin rash (4/6) were the most common clinical features of CDC. Four children grew Candida tropicalis from blood or skin. CDC-related IRIS was documented in 5 children (83%) and 2 received corticosteroids. Our literature review revealed that 28 children were managed with corticosteroids for CDC-related IRIS since 2005. The majority of these children had defervescence of fever within 48 hours. Prednisolone of 1-2 mg/kg/day for 2-6 weeks was the most common regimen used. No major side effects reported in these patients. CONCLUSION: CDC is more common in children with acute leukemia and CDC-related IRIS is not uncommon. Corticosteroid therapy looks effective and safe as adjunctive therapy for CDC-related IRIS.

Bacterial vs viral etiology of fever: A prospective study of a host score for supporting etiologic accuracy of emergency department physicians.

BACKGROUND: A host-protein score (BV score) that combines the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10) and C-reactive protein (CRP) was developed for distinguishing bacterial from viral infection. This study assessed the potential of the BV score to impact decision making and antibiotic stewardship at the emergency department (ED), by comparing BV score's performance to physician's etiological suspicion at patient presentation. METHODS: Rosetta study participants, aged 3 months to 18 years with febrile respiratory tract infection or fever without source, were prospectively recruited in a tertiary care pediatric ED. 465 patients were recruited, 298 met eligibility criteria and 287 were enrolled. ED physician's etiological suspicion was recorded in a questionnaire. BV score was measured retrospectively with results interpreted as viral, bacterial or equivocal and compared to reference standard etiology, which was adjudicated by three independent experts based on all available data. Experts were blinded to BV scores. RESULTS: Median age was 1.3 years (interquartile range 1.7), 39.7% females. 196 cases were reference standard viral and 18 cases were reference standard bacterial. BV score attained sensitivity of 88.9% (95% confidence interval: 74.4-100), specificity 92.1% (88.1-96.0), positive predictive value 53.3% (35.5-71.2) and negative predictive value 98.8% (97.1-100). Positive likelihood ratio was 11.18 (6.59-18.97) and negative likelihood ratio was 0.12 (0.03-0.45). The rate of BV equivocal scores was 9.4%. Comparing physician's suspicion to BV score and to the reference standard, and assuming full adoption, BV score could potentially correct the physician's diagnosis and reduce error ~2-fold, from 15.9% to 8.2%. CONCLUSIONS: BV score has potential to aid the diagnostic process. Future studies are warranted to assess the impact of real-time BV results on ED practice.

Temperature threshold in the screening of bacterial infections in young infants with hypothermia.

BACKGROUND: Young infants with hypothermia presenting to the emergency department (ED) are at risk for serious bacterial infections (SBI), however there is no consensus temperature to prompt evaluation for SBI among these children. We sought to statistically derive a temperature threshold to guide detection of SBI in young infants with hypothermia presenting to the ED. METHODS: We performed a cross-sectional study of infants ≤90 days old presenting to four academic paediatric EDs in the United States of America from January 2015 through December 2019 with a rectal temperature of ≤36.4°C. Our primary outcomes were SBI, defined as urinary tract infection (UTI), bacteraemia and/or bacterial meningitis, and invasive bacterial infections (IBI, limited to bacteraemia and/or bacterial meningitis). We constructed receiver operating characteristic (ROC) curves to evaluate an optimally derived cutpoint for minimum ED temperature and presence of SBI or IBI. RESULTS: We included 3376 infants, of whom SBI were found in 62 (1.8%) and IBI in 16 (0.5%). The most common infection identified was Escherichia coli UTI. Overall, cohort minimum median temperature was 36.2°C (IQR 36.0°C-36.4°C). Patients with SBI and IBI had lower median temperatures, 35.8°C (IQR 35.8°C-36.3°C) and 35.4°C (IQR 35.7°C-36.3°C), respectively, compared with those without corresponding infections (both p<0.05). Using an outcome of SBI, the area under the ROC curve (AUROC) was 61.0% (95% CI 54.1% to 67.9%). At a cutpoint of 36.2°C, sensitivity was 59.7% and specificity was 59.2%. When using an outcome of IBI, the AUROC was 65.9% (95% CI 51.1% to 80.6%). Using a cutpoint of 36.1°C in this model resulted in a sensitivity of 68.8% and specificity of 60.1%. CONCLUSION: Young infants with SBI and IBI presented with lower temperatures than infants without infections. However, there was no temperature threshold to reliably identify SBI or IBI. Further research incorporating clinical and laboratory parameters, in addition to temperature, may help to improve risk stratification for these vulnerable patients.

[An intracranial haemorrhage in a febrile newborn]. / L'image du mois. Une hémorragie intracrânienne chez un nouveau-né fébrile.

A 15 days old newborn was admitted to the emergency room for a recent fever onset. In newborns, the priority is to rule out any bacterial infection and initiate broad spectrum antibiotics. The hemorrhagic appearance of the cerebrospinal fluid after lumbar puncture can sometimes be the only sign to suspect, other than obvious infectious aetiology, an intracranial haemorrhage.

: Un nouveau-né de 15 jours est admis en salle d'urgence pour de la fièvre. Au vu de l'immaturité immunitaire des nouveau-nés et selon les recommandations internationales, la priorité est d'exclure une infection d'origine bactérienne et d'administrer une antibiothérapie intraveineuse empirique. Lors de la réalisation du bilan étiologique, l'aspect hémorragique du liquide céphalo-rachidien peut être le témoin d'un syndrome méningé d'étiologie autre qu'infectieuse, et notamment d'une hémorragie intracérébrale.

Trends in Prevalence of Bacterial Infections in Febrile Infants During the COVID-19 Pandemic.

OBJECTIVES: Our objective was to describe the prevalence of urinary tract infection (UTI) and invasive bacterial infection (IBI) in febrile infants during the coronavirus disease 2019 pandemic. METHODS: We conducted a multicenter cross-sectional study that included 97 hospitals in the United States and Canada. We included full-term, well-appearing infants 8 to 60 days old with a temperature of ≥38°C and an emergency department visit or hospitalization at a participating site between November 1, 2020 and March 31, 2022. We used logistic regression to determine trends in the odds of an infant having UTI and IBI by study month and to determine the association of COVID-19 prevalence with the odds of an infant having UTI and IBI. RESULTS: We included 9112 infants; 603 (6.6%) had UTI, 163 (1.8%) had bacteremia without meningitis, and 43 (0.5%) had bacterial meningitis. UTI prevalence decreased from 11.2% in November 2020 to 3.0% in January 2022. IBI prevalence was highest in February 2021 (6.1%) and decreased to 0.4% in January 2022. There was a significant downward monthly trend for odds of UTI (odds ratio [OR] 0.93; 95% confidence interval [CI]: 0.91-0.94) and IBI (OR 0.90; 95% CI: 0.87-0.93). For every 5% increase in COVID-19 prevalence in the month of presentation, the odds of an infant having UTI (OR 0.97; 95% CI: 0.96-0.98) or bacteremia without meningitis decreased (OR 0.94; 95% CI: 0.88-0.99). CONCLUSIONS: The prevalence of UTI and IBI in eligible febrile infants decreased to previously published, prepandemic levels by early 2022. Higher monthly COVID-19 prevalence was associated with lower odds of UTI and bacteremia.