Febrile Children Research Articles

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

ObjectiveTo 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.DesignInternational, multicentre,...

Fever in focus: Symptoms, diagnoses and treatment of febrile children in Ghana-A longitudinal hospital study.

Healthcare resources are often limited in areas of sub-Saharan Africa. This makes accurate and timely diagnoses challenging and delays treatment of childhood febrile illness. We explored longitudinal characteristics related to symptoms, diagnosis and treatment of hospitalised febrile children in a rural area of Ghana highly endemic for malaria. Febrile children under 15 years, admitted to the study hospital paediatric ward, were recruited to the study and clinical data were collected throughout hospitalisation. Descriptive statistics were reported for all cases; for longitudinal analyses, a subset of visits with limited missing data was used. There were 801 hospitalised children included in longitudinal analyses. Malaria (n = 581, 73%) and sepsis (n = 373, 47%) were the most prevalent suspected diagnoses on admission. One-third of malaria suspected diagnoses (n = 192, 33%) were changed on the discharge diagnosis, compared to 84% (n = 315) of sepsis suspected diagnoses. Among malaria-only discharge diagnoses, 98% (n/N = 202/207) received an antimalarial and 33% (n/N = 69/207) an antibiotic; among discharge diagnoses without malaria, 28% (n/N = 108/389) received an antimalarial and 83% (n/N = 324/389) an antibiotic. Suspected diagnoses were largely based on clinical presentation and were frequently changed; changed diagnoses were associated with lingering symptoms, underscoring the need for faster and more accurate diagnostics. Medications were over-prescribed regardless of diagnosis stability, possibly because of a lack of confidence in suspected diagnoses. Thus, better diagnostic tools are needed for childhood febrile illnesses to enhance the accuracy of and confidence in diagnoses, and to cut down unjustified medication use, reducing the risk of antimicrobial and malaria resistance.

Prognostic performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal procalcitonin

IntroductionIt is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT. MethodsThis was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia. ResultsIn total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia. ConclusionsIL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.

EaveTubes for control of vector-borne diseases in Côte d’Ivoire: study protocol for a cluster randomized controlled trial

BackgroundVector control tools, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), have significantly contributed to malaria prevention efforts in sub-Saharan Africa. However, insecticide resistance has seriously hampered their efficacy in recent years and new tools are essential to further progress. In2Care® EaveTubes (ETs) are an inexpensive, new resistance-breaking vector control product under World Health Organization (WHO) evaluation informed by mosquito ecology to efficiently target malaria vectors. By installing ETs in the walls of the house at the eave level that funnel the natural airflow, mosquitoes are drawn in by the same heat and odor cues that typically attract them through open eaves. Once inside an ET, mosquitoes are exposed to insecticide-treated netting placed inside the ET. The aim of this study is to test whether ETs as stand-alone tool have an effect on the epidemiology of malaria in villages where houses have been modified with the ET intervention.MethodsA two-armed, cluster randomized controlled trial will be conducted to evaluate the effect of ETs on clinical malaria incidence in children living in Côte d’Ivoire. Thirty-four villages will be selected based on population size and the proportion of houses suitable for modification with ETs (17 treatment arms (ETs + LLINs, 17 control arms (LLINs only)). Based on the population census, 55 households per cluster with eligible children (i.e., between the ages of 6 months to 8 years old at the start of the study) will be randomly selected for recruitment into the active detection cohorts. In the treatment arm, we will enroll eligible children who reside in ET-treated houses. The intervention and control cohorts will be followed for 4 months for baseline covariate measurements and 24 months with intervention. During case detection visits, blood samples will be taken from all febrile children and tested for malaria infection with rapid diagnostic tests (RDTs). All positive clinical malaria infections will be treated. To estimate the impact of the ET on malaria vector densities, entomological measurements (indoor sampling with CDC traps) will be conducted monthly in 20 clusters (10 ET, 10 Control) in 10 randomly selected households per cluster. To estimate the infectiousness of malaria vectors, sporozoite rates will be measured in subsets of the collected mosquito samples.DiscussionFindings will serve as an efficacy trial of ETs and will be submitted to the WHO Vector Control Advisory Group (VCAG) for assessment of public health value. Entomological outcomes will also be measured as proxies of malaria transmission to help develop guidelines for the evaluation of future In2Care® ETs products.Trial registrationClinicalTrials.gov NCT05736679. Registered on 10 February 2023.

Diagnostic Accuracy of a Real-Time Host-Protein Testfor Infection.

Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV's diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician's discretion. Patients aged 3 months to 18 years were retrospectively recruited (NCT03075111; SPIRIT study; 2014-2017). Emergency department physician's etiological suspicion and certainty level were recorded in a questionnaire at blood-draw. MMBV results are based on predefined score thresholds: viral/non-bacterial etiology (0 ≤ score <35), equivocal (35 ≤ score ≤65), and bacterial or coinfection (65 < score ≤100). Reference standard etiology (bacterial/viral/indeterminate) was adjudicated by 3 independent experts based on all available patient data. Experts were blinded to MMBV. MMBV and physician's etiological suspicion were assessed against the reference standard. Of 3003 potentially eligible patients, the physicians were uncertain about infection etiology for 736 of the cases assigned a reference standard (128 bacterial, 608 viral). MMBV performed with sensitivity 89.7% (96/107; 95% confidence interval 82.4-94.3) and specificity 92.6% (498/538; 95% confidence interval 90.0-94.5), significantly outperforming physician's etiological suspicion (sensitivity 49/74 = 66.2%, specificity 265/368 = 72.0%; P < .0001). MMBV equivocal rate was 12.4% (91/736). MMBV was more accurate in determining etiology compared with physician's suspicion and had high sensitivity and specificity according to the reference standard.

Kawasaki Disease Associated Acute Abdomen: Most Require No Surgery.

To summarize the clinical features and treatment experiences of patients with Kawasaki disease (KD)-associated acute abdomen (KD-AA). We conducted a retrospective case-control study of patients with KD-AA treated at our hospital between January 2006 and November 2022. Of the 917 children with KD, 43 (4.7%) presented with AA. Of these, 33 with complete information were included in the KD-AA group. Patients with KD-AA were significantly older, with higher neutrophil rate, C-reactive protein, procalcitonin, and alanine transaminase levels and lower hemoglobin, albumin, and serum sodium levels. Additionally, more patients with KD-AA presented with aseptic meningitis and KD shock syndrome than those with KD alone (all p<0.05). The two groups did not differ in the incidence of intravenous immunoglobulin (IVIG) resistance, incomplete KD, or coronary artery abnormalities. All patients received aspirin and IVIG therapy, with nine receiving a second dose of IVIG and 11 receiving corticosteroids. Only two patients with KD-AA underwent surgery, and the prognosis of all patients with KD-AA was good. KD-AA should be suspected in febrile children with abdominal symptoms. Prompt diagnosis of KD-AA is important for early effective treatment to avoid unnecessary surgical harm. KD, complicated by acute abdomen, has a good prognosis.

Heliotrope like rash in a febrile child: think of Kawasaki disease.

Heliotrope like rash in a febrile child: think of Kawasaki disease.

Development and validation of a predictive model for febrile seizures

Febrile seizures (FS) are the most prevalent type of seizures in children. Existing predictive models for FS exhibit limited predictive ability. To build a better-performing predictive model, a retrospective analysis study was conducted on febrile children who visited the Children's Hospital of Shanghai from July 2020 to March 2021. These children were divided into training set (n = 1453), internal validation set (n = 623) and external validation set (n = 778). The variables included demographic data and complete blood counts (CBCs). The least absolute shrinkage and selection operator (LASSO) method was used to select the predictors of FS. Multivariate logistic regression analysis was used to develop a predictive model. The coefficients derived from the multivariate logistic regression were used to construct a nomogram that predicts the probability of FS. The calibration plot, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were used to evaluate model performance. Results showed that the AUC of the predictive model in the training set was 0.884 (95% CI 0.861 to 0.908, p < 0.001) and C-statistic of the nomogram was 0.884. The AUC of internal validation set was 0.883 (95% CI 0.844 to 0.922, p < 0.001), and the AUC of external validation set was 0.858 (95% CI 0.820 to 0.896, p < 0.001). In conclusion, the FS predictive model constructed based on CBCs in this study exhibits good predictive ability and has clinical application value.

A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM): a multi-cohort machine learning study

Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. 376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma samples for the MS-A dataset, and 150 plasma samples for the MS-B dataset. Differential abundance analysis, and the first round of feature selection using FS-PLS identified 35 protein biomarker candidates, of which 13 had commercial ELISA or Luminex tests available. 16 proteins with ELISA or Luminex tests available were identified by literature review. Further evaluation via Luminex and ELISA and the second round of feature selection using FS-PLS revealed a six-protein signature: three of the included proteins are elevated in bacterial infections (SELE, NGAL, and IFN-γ), and three are elevated in viral infections (IL18, NCAM1, and LG3BP). Performance testing of the signature using Luminex assays revealed area under the receiver operating characteristic curve values between 89·4% and 93·6%. This study has led to the identification of a protein signature that could be ultimately developed into a blood-based point-of-care diagnostic test for rapidly diagnosing bacterial and viral infections in febrile children. Such a test has the potential to greatly improve care of children who are febrile, ensuring that the correct individuals receive antibiotics. European Union's Horizon 2020 research and innovation programme, the European Union's Seventh Framework Programme (EUCLIDS), Imperial Biomedical Research Centre of the National Institute for Health Research, the Wellcome Trust and Medical Research Foundation, Instituto de Salud Carlos III, Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Grupos de Refeencia Competitiva, Swiss State Secretariat for Education, Research and Innovation.

Microbiological Profiles and Inflammatory Biomarkers of Bacteremia in Children in a Teaching Hospital in Kuwait: An 8-Year Retrospective Study

Objectives: The objectives of this study were to determine the bacterial profiles and prevalence of antibiotic resistance patterns of bacteria causing bacteremia in febrile children and to compare levels of inflammatory markers between children with and without bacteremia in Kuwait from 2015 to 2022. Materials and Methods: Isolates from all episodes of significant bacteremia (n = 96) during the study period were recorded and evaluated. Microorganisms were identified using standard microbiological methods. Antimicrobial susceptibility testing was carried out using the VITEK2 system and Etest method. Extended-spectrum β-lactamase (ESBL) production by Enterobacterales was detected by the double-disk diffusion method and VITEK2 system. Patient age, gender, and inflammatory markers were collected at admission and compared between patients with and without bacteremia. Results: A majority of the patients were infants (37, 40%) and newborns (13, 14%). The main ports of entry were the lower respiratory tract, the genitourinary tract, and the gastrointestinal tract. Streptococcus pneumoniae was the most common pathogen (16, 16.7%) followed by Escherichia coli (12, 12.5%), Staphylococcus aureus (10, 10.4%), and Streptococcus agalactiae (9, 9.4%). High rates of resistance to ampicillin, cefuroxime, ciprofloxacin, and trimethoprim-sulfamethoxazole were observed among the Enterobacterales. The prevalence of ESBL-producing E. coli and K. pneumoniae were 45% and 29%, respectively. The prevalence of methicillin-resistant S. aureus was 30%. Patients with bacteremia had significantly higher white blood cell (WBC) counts, absolute neutrophil count (ANC), C-reactive protein (CRP), and neutrophil-lymphocyte ratio (NLR). Conclusion: Continuous surveillance of the prevalence and antimicrobial susceptibility patterns of blood isolates is imperative for the formulation of antibiotic policy. WBC, ANC, CRP, and NLR could be valuable indicators of bacteremia in febrile children.

Raising AWaRe-ness of Antimicrobial Stewardship Challenges in Pediatric Emergency Care: Results from the PERFORM Study Assessing Consistency and Appropriateness of Antibiotic Prescribing Across Europe.

Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final "bacterial" or "viral" phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/β-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the "Watch" category. Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics. A significant proportion of patients with a viral phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology could significantly improve antimicrobial stewardship.

The CD19+ B cell as a marker for the febrile children infected with influenza A and Omicron variant.

H3N2 and Omicron are common pathogens of respiratory infections in children. This study aimed to explore dynamic changes of lymphocyte subsets and the diagnostic value of CD19+ B cell in children infected with influenza A and Omicron. One hundred and sixty-five in-patients with H3N2, 175 in-patients with Omicron variant, and 50 age-matched healthy children from Children's Hospital of Soochow University were included in this study. The participants underwent 13 respiratory pathogens by DNA polymerase chain reaction (PCR), sputum culture, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) DNA PCR, routine blood, and lymphocyte subset assays within 24 h of admission. The neutrophils, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in the H3N2 and Omicron groups were significantly higher than in the control groups (p < 0.05). However, the lymphocytes and eosinophils in the H3N2 and Omicron groups were lower than the control groups (p < 0.05). The CD3+ T cell, CD3+ CD4+ T cell, CD3+ CD8+ T cell, CD3- CD19+ B cell, and natural killer cell were lower in the H3N2 and Omicron groups than in the control group (p < 0.05). The CD3- CD19+ cell in the Omicron group was higher than that in the H3N2 group but lower than that in the control group (p < 0.05). In addition, CD3- CD19+ cell had good diagnostic value for H3N2 (area under the receiver operating characteristic curve = 0.902, p < 0.05). The children with H3N2 were more likely to have lower lymphocytes than children with Omicron. Additionally, B-cell count had good diagnostic value for H3N2.

FACTORS INFLUENCING THE UTILIZATION OF MALARIA HOME-BASED MANAGEMENT IN KICUKIRO DISTRICT, RWANDA

Malaria is still one of the most critical cause of deaths globally each year. The year of 2020 was marked by the report of 627,000 deaths and 241 million cases due to malaria. Malaria home-based management (MHBM) progress was hampered while malaria-carrying vectors are still dominant with malaria incidence increase in Rwanda. This study aimed to assess the factors associated with the utilization of MHBM program among the study participants in Kicukiro District. This cross-sectional study design included 312 study respondents who were trained community health workers and their respective health care seekers (people with malaria or febrile sick children). This sample size was obtained by Yamane sample size formula. Univariate, bivariate, and multivariate data analysis were conducted with SPSS 21 version. The significance was accepted at a p-value of 0.05 with 95%CI. Overall findings revealed that the Household MHBM high utilization was (55.8%) while 44.2% had low level of MHBM utilization among study participants in Kicukiro District. Having three or more children, seeking malaria home-based treatment to the CHWs you really know, using nearest CHW were significantly associated with the MHBM with AoR=3.133, 95% CI=1.692-5.810 and p &lt;0.001; AoR=2.2, 95% CI= 1.202-4.223, p&lt;0.001; AoR =4.9, 95%CI= 2.043-7.103, p&lt;0.001. Additionally, having required materials to ease the work of CHWs which may let MHBM service seekers come, MHBM daily schedule, usual work of the CHWs which doesn’t conflict with MHBM were highly and significantly associated with MHBM utilization. Their respective adjusted odd ratios were: AoR=4.472,95% CI=2.614-9.555, p=0.007; AoR=8.787,95% CI=4.045-14.592&lt;0.001; AoR=6.362, 95% CI, 2.252-11.158, p&lt;0.001. This study concluded that strengthening the community health workers requires four essential strategic components. The training of community health workers to reach out the community in their respective operation areas, improving their social connection, constant reviewing and refill their required materials and finally, planning improvement in their service delivery.

47 Clinical Approach to Febrile Urinary Tract Infections in Young Children Presenting to the Paediatric Emergency Department: A Retrospective Study of National Guideline Compliance

Abstract Background Antimicrobial resistance is one of the greatest threats to global health. Antibiotic overuse drives antimicrobial resistance. Suspected urinary tract infection (UTI) is a key area of over-prescribing in many clinical settings but has not been investigated in the paediatric emergency department (ED). Objectives Here, we explore compliance with national UTI management guidelines in a paediatric emergency department setting and characterize patient and provider factors associated with guideline non-compliance. Design/Methods We performed retrospective chart review of patients ages 60 days to 36 months, discharged with a diagnosis of UTI from a single, urban, tertiary care paediatric emergency department (PED) with a diagnosis of UTI. Random visits were chosen using a computer algorithm. Primary outcomes were: 1) proportion of patients receiving guideline-compliant investigation and treatment, and 2) the proportion of children whose antibiotic prescriptions were appropriately adjusted upon return of urine culture and antibiotic susceptibilities (C&amp;S). The guideline was the Canadian Paediatric Society statement on management of UTI, as well as the BC Children’s Hospital institutional UTI management guideline. Descriptive statistics and odds ratios between associations were calculated. Results We reviewed 402 charts. The proportion of infants receiving guideline-compliant testing and treatment was 25.9% (95% CI: 21.8-30.4%). Of those who were prescribed antibiotics, 79.6% (95% CI: 74.7-83.8%) received a first-line recommended agent and 58.9% (95% CI: 53.8-63.8%) received fully compliant therapy with respect to agent, dose, duration, and frequency. 19.4% (15.4-24.2%) of patients who were prescribed empiric cephalexin received an inappropriately high total daily dose. The proportion of patients receiving age-appropriate testing method was 52.2% (95% CI: 47.4-57.1). Febrile children were more likely to receive age-appropriate urine sample collection by catheterized sample (OR: 2.77 95% CI: 1.81-4.25) compared with afebrile children. Ultimately, 50.7% (95% CI: 40.4-49.6%) of patients discharged with a diagnosis of UTI and prescription for antibiotic met diagnostic criteria for UTI based on urinalysis and culture results. Of patients whose C&amp;S mandated a change in therapy, 60.8% (95% CI: 55.8-65.7%) had their agent changed or discontinued. Conclusion Paediatric emergency medicine physicians frequently order inappropriate investigation and empiric treatment of UTI in young children. Discontinuation of empiric antibiotics in culture-negative children may be an impactful stewardship intervention in the PED.

Antibiotic Prescribing for Lower Respiratory Tract Infections and Community-Acquired Pneumonia: An Italian Pediatric Emergency Department's Real-Life Experience.

Lower respiratory tract infections (LRTIs) and community-acquired pneumonia (CAP) are among the most frequent reasons for referrals to the pediatric emergency department (PED). The aim of this study is to describe the management of antibiotic prescription in febrile children with LRTI or CAP admitted to a third-level PED and to investigate the different variables that can guide physicians in this decision-making. This is an observational, retrospective, monocentric study including patients < 14 years old who were presented to the PED for a febrile LRTI or CAP during the first six months of the year 2017. Demographic and clinical data, PED examinations, recommended therapy, and discharge modality were considered. Two multivariate logistic regression analyses were performed on patients with complete profiles to investigate the impact of demographic, laboratory, and clinical variables on antibiotic prescription and hospital admission. This study included 584 patients with LRTI (n = 368) or CAP (n = 216). One hundred and sixty-eight individuals (28.7%) were admitted to the hospital. Lower age, higher heart rate, and lower SpO2 were associated with an increased risk of hospitalization. Antibiotics were prescribed to 495 (84.8%) patients. According to the multivariate logistic regression, the diagnosis and duration of fever were substantially linked with antibiotic prescription. The present study reports real-life data about our PED experience. A high rate of antibiotic prescription was noted. In the future, it is necessary to improve antibiotic stewardship programs to increase clinical adherence to guidelines.

Support for the Use of a New Cutoff to Define a Positive Urine Culture in Young Children.

Conventional urine culture selects for a narrow range of organisms that grow well in aerobic conditions. In contrast, examination of bacterial gene sequences in the urine provides a relatively unbiased evaluation of the organisms present. Thus, by using 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing as the reference standard, we now have the ability to assess the accuracy of urine culture in diagnosing urinary tract infection (UTI). We enrolled febrile children 1 month to 3 years of age that underwent bladder catheterization for suspected UTI. Using 16S rRNA gene amplicon sequencing as the reference standard, we calculated the accuracy of urine culture at various cutoffs (10 000, 50 000, and 100 000 colony forming units per milliliter). Children with ≥80% relative abundance of any organism on 16S rRNA gene amplicon sequencing with elevated urinary markers of inflammation were defined as having a UTI. When using a cutoff of 10 000 CFU/mL, the sensitivity and specificity of urine culture were 98% (95% confidence interval [CI]: 93%-100%) and 99% (95% CI: 97%-100%), respectively. Using a cutoff of 50 000 colony forming units per mL decreased sensitivity to 80% (95% CI: 68%-93%) without changing the specificity. Using a cutoff of 100 000 further decreased sensitivity to 70% (95% CI: 55%-84%). Conventional culture remains an accurate method of diagnosing UTIs in young children; however, these data suggest that a cutoff of 10 000 colony forming units per mL provides the optimal balance between sensitivity and specificity for children undergoing bladder catheterization.

Rapid molecular diagnostic tests fail to PERFORM in febrile children.

Rapid molecular diagnostic tests fail to PERFORM in febrile children.

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.

The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N.meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S.pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E.coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. EU Horizon 2020 grant 668303.

Clinical relevance of blood urea nitrogen to serum albumin ratio for predicting bacteremia in very young children with febrile urinary tract infection.

Urinary tract infections (UTIs) are one of the most common bacterial infections in febrile children and a common cause of hospitalization, especially in very young children. We examined the clinical characteristics and predictive factors of concomitant bacteremia in pediatric patients with febrile UTI aged ≤24 months. This retrospective multicenter study reviewed medical data from 2,141 patients from three centers from January 2000 to December 2019. Enrolled cases were classified into the bacteremic UTI and non-bacteremic UTI groups according to the presence of blood culture pathogens. Among 2,141 patients with febrile UTI, 40 (1.9%) had concomitant bacteremia. All patients in the bacterial group were aged ≤6 months. Multivariate analysis revealed that younger age, lower blood lymphocyte counts and serum albumin levels, higher C-reactive protein (CRP) levels, blood urea nitrogen (BUN) levels, and BUN/serum albumin ratio were independent risk factors of concomitant bacteremia. The area under the receiver-operating characteristic curves predicting bacteremia were 0.668 for CRP, 0.673 for lymphocytes, and 0.759 for the BUN/albumin ratio. The present study identified the BUN/albumin ratio and lower blood lymphocyte counts as novel predictive factors for bacteremia in young infants with febrile UTI in addition to the previously identified factors of younger age and higher CRP levels. Our findings could help to identify patients at high risk of bacteremia and benefit decision-making in the management of infants with febrile UTI.

Mortality after emergency unit fluid bolus in febrile Ugandan children.

Pediatric fluid resuscitation in sub-Saharan Africa has traditionally occurred in inpatients. The landmark Fluid Expansion as Supportive Therapy (FEAST) trial showed fluid boluses for febrile children in this inpatient setting increased mortality. As emergency care expands in sub-Saharan Africa, fluid resuscitation increasingly occurs in the emergency unit. The objective of this study was to determine the mortality impact of emergency unit fluid resuscitation on febrile pediatric patients in Uganda. This retrospective cohort study used data from 2012-2019 from a single emergency unit in rural Western Uganda to compare three-day mortality for febrile patients that did and did not receive fluids in the emergency unit. Propensity score matching was used to create matched cohorts. Crude and multivariable logistic regression analysis (using both complete case analysis and multiple imputation) were performed on matched and unmatched cohorts. Sensitivity analysis was done separately for patients meeting FEAST inclusion and exclusion criteria. The analysis included 3087 febrile patients aged 2 months to 12 years with 1,526 patients receiving fluids and 1,561 not receiving fluids. The matched cohorts each had 1,180 patients. Overall mortality was 4.0%. No significant mortality benefit or harm was shown in the crude unmatched (Odds Ratio [95% Confidence Interval] = 0.88 [0.61-1.26] or crude matched (1.00 [0.66-1.50]) cohorts. Adjusted cohort analysis (including both complete case analysis and multiple imputation) and sensitivity analysis of patients meeting FEAST inclusion and exclusion criteria all also failed to show benefit or harm. Post-hoc power calculations showed the study was powered to detect the absolute harm seen in FEAST but not the relative risk increase. This study's primary finding is that fluid resuscitation in the emergency unit did not significantly increase or decrease three-day mortality for febrile children in Uganda. Universally aggressive or fluid-sparing emergency unit protocols are unlikely to be best practices, and choices about fluid resuscitation should be individualized.