BACKGROUND: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.METHODS: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.RESULTS: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.CONCLUSIONS: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.

Background The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.Methods 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.Findings 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.Interpretation 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.Funding EU Horizon 2020 grant 668303. Copyright & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability. Methods and findings A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks. Questions focused on the availability and use of currently available POCTs. Data were analysed descriptively and using Median Odds Ratio (MOR) to measure variation between countries. Multilevel regression modelling using changes in the area under the receiver operating characteristic curve of models were used to assess the contribution of individual or workplace versus country level factors, to the observed variation. The commonest POCT was urine dipsticks (UD) which were available to >80% of primary care and hospital paediatricians in 68% (13/19) and 79% (23/29) countries, respectively. Availability of all POCTs varied between countries. In primary care, the country (MOR) varied from 1.61 (95%CI: 1.04-2.58) for lactate to 7.28 (95%CI: 3.04-24.35) for UD. In hospitals, the country MOR varied from 1.37 (95%CI:1.04-1.80) for lactate to 11.93 (95%CI:3.35-72.23) for UD. Most paediatricians in primary care (69%, 795/1154) and hospital (81%, 962/1188) would use a diagnostic test in the case scenario of an infant with undifferentiated fever. Multilevel regression modelling showed that the country of work was more important in predicting both the availability and use of POCTs than individual or workplace characteristics. Conclusion There is substantial variability in the adoption of POCTs for the management of acute infections in children across Europe. To inform future implementation of both existing and innovative tests, further research is needed to understand what drives the variation between countries, the needs of frontline clinicians, and the role of diagnostic tests in the management of acute childhood infections.

Background: Current management of febrile children aims to distinguish the minority with bacterial infection from the majority with viral illness. The Personalized Risk assessment in Febrile illness to Optimise Real-life Management (PERFORM) multi-country observational study aimed to understand the microbiological causes of febrile illness in European children through comparison of molecular pathogen detection and assignment of illness based on current clinical practice.Methods: Centralized molecular tests (CMT) for 19 respiratory and 27 blood pathogens were evaluated in all children with available samples. Each child was assigned to a standardized diagnostic category, based on retrospective review of clinical data, including 'best practice' local microbiological investigations, and blinded to results from CMT.Findings: Of 4,334 febrile children, 608(14%) were classified as having definite bacterial infection (DB), 447(10%) as having definite viral infection (DV), the remaining 3,289(76%) had uncertain etiology. Additionally 944 controls were included. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (odds ratio (OR): 3.37, 95% confidence interval (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, Influenza B and RSV were more common in DV than DB cases (OR and 95%CI for detection in DB vs DV cases 0.25 [0.11-0.46], 0.12 [0.02-0.37] and 0.16 [0.06-0.36] respectively). Two of 16 blood viruses were detected more often in DV than DB cases - enterovirus and EBV (OR and 95%CI for detection in DB vs DV cases 0.43[0.23-0.72] and 0.71[0.56-0.90] respectively). Combined local diagnostics and CMT detected blood viruses in 56% of DB cases, and respiratory viruses in 25%. Detection of a virus in blood or respiratory swabs were poor predictors for ruling-out bacterial infection, with predictive values of 0.64 and 0.68 respectively.Interpretation: Viruses are detected in a high proportion of patients with bacterial infection. The data challenge the concept that bacterial and viral infections are separate pathological events that should be managed with a corresponding dichotomous approach. The sensitivity and specificity of pathogen detection as snapshots were insufficient to determine the most appropriate clinical intervention, including the need for antibiotics and highlights the need for new approaches to managing febrile children.Funding Information: PERFORM was funded by the European Union’s Horizon 2020 program under GA No 668303. Enrolment of patients in UK was supported by NIHR Biomedical Research Centres at Imperial College London, and Newcastle.Declaration of Interests: None declared.Ethics Approval Statement: Ethical approval was obtained at the coordinating site (Imperial College London, 16/LO/1684) and separately at each participating center, using a consortium-wide clinical study protocol. All patients were recruited with informed parental consent, and assent from older children.