Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments: MOFICHE, a prospective observational study
Nienke N. Hagedoorn, Dorine Borensztajn, Ruud Nijman, Daan Nieboer, Jethro Herberg, Anda Balode, Ulrich von Both, Enitan D. Carrol, Irini Eleftheriou, Marieke Emonts, Michiel van der Flier, Ronald de Groot, Benno Kohlmaier, Emma Lim, Ian Maconochie, Federico Martinón‐Torres, Marko Pokorn, Franc Strle, Μαρία Τσολιά, Dace Zavadska, Werner Zenz, Michael Levin, Clementien L. Vermont, Henriëtte A. Moll
Abstract
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.