Objectives To develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers.
Design Prospective observational study.
Setting 12 emergency departments (EDs) in 8 European countries.
Patients Febrile children aged 0–18 years.
Main outcome measures IBI, defined as bacteraemia, meningitis and bone/joint infection. We derived and cross-validated a model for IBI using variables from the Feverkidstool (clinical symptoms, C reactive protein), neurological signs, non-blanching rash and comorbidity. We assessed discrimination (area under the receiver operating curve) and diagnostic performance at different risk thresholds for IBI: sensitivity, specificity, negative and positive likelihood ratios (LRs).
Results Of 16 268 patients, 135 (0.8%) had an IBI. The discriminative ability of the model was 0.84 (95% CI 0.81 to 0.88) and 0.78 (95% CI 0.74 to 0.82) in pooled cross-validations. The model performed well for the rule-out threshold of 0.1% (sensitivity 0.97 (95% CI 0.93 to 0.99), negative LR 0.1 (95% CI 0.0 to 0.2) and for the rule-in threshold of 2.0% (specificity 0.94 (95% CI 0.94 to 0.95), positive LR 8.4 (95% CI 6.9 to 10.0)). The intermediate thresholds of 0.1%–2.0% performed poorly (ranges: sensitivity 0.59–0.93, negative LR 0.14–0.57, specificity 0.52–0.88, positive LR 1.9–4.8) and comprised 9784 patients (60%).
Conclusions The rule-out threshold of this model has potential to reduce antibiotic treatment while the rule-in threshold could be used to target treatment in febrile children at the ED. In more than half of patients at intermediate risk, sensitive biomarkers could improve identification of IBI and potentially reduce unnecessary antibiotic prescriptions.
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Correction notice This paper has been amended since it was published online. The data sharing statement has been updated.
Contributors Conceptualisation: NNH, DB, RGN, DN, JAH, AB, UvB, EC, IE, ME, MvdF, RdG, BK, EL, IM, FM-T, MP, FS, MT, DZ, WZ, ML, CV, HAM. Data curation: NNH, DB, RGN, JAH, AB, UvB, EC, IE, ME, MvdF, RdG, JAH, BK, EL, IM, FM-T, MP, FS, MT, DZ, WZ, ML, CV, HAM. Formal analysis: NNH, DN. Methodology: NNH, DB, RGN, DN, JAH, AB, UvB, EC, IE, ME, MvdF, RdG, BK, EL, FM-T, DN, MP, MT, DZ, CV, WZ, ML, HAM. Supervision: CV, HAM. Writing—original draft: NNH. Writing—review and editing: NNH, DB, RN, DN, JAH, AB, UvB, EC, IE, ME, MvdF, RdG, BK, EL, IM, FM-T, MP, FS, MT, DZ, WZ, ML, CV, HAM.
Funding This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 668303. The research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University.
Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Competing interests None declared.
Patient and public involvement statement The design of the study did not involve patients. The study results will be disseminated to members of the public, patients and experts through social media and networks.
Patient consent for publication Not required.
Ethics approval The study was approved by all the participating hospitals. No informed consent was needed for this study. Austria (Ethikkommission Medizinische Universitat Graz, ID: 28-518 ex 15/16), Germany (Ethikkommission Bei Der LMU München, ID: 699-16), Greece (Ethics committee, ID: 9683/18.07.2016), Latvia (Centrala medicinas etikas komiteja, ID: 14.07.201 6. No. Il 16-07-14), Slovenia (Republic of Slovenia National Medical Ethics Committee, ID: ID: 0120-483/2016-3), Spain (Comité Autonómico de Ética de la Investigación de Galicia, ID: 2016/331), The Netherlands (Commissie Mensgebonden onderzoek, ID: NL58103.091.16), UK (Ethics Committee, ID: 16/LO/1684, IRAS application no. 209035, confidentiality advisory group reference: 16/CAG/0136).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement An anonymized data set containing individual participant data is available in a public data repository: https://data.hpc.imperial.ac.uk/resolve/?doi=7549. DOI: 10.14469/hpc/7549. For inquiries to obtain the full dataset, please contact the data manager of the PERFORM consortium (Tisham.firstname.lastname@example.org. uk).
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