Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE): A multicentre observational study

Autoři: Nienke N. Hagedoorn aff001;  Dorine M. Borensztajn aff001;  Ruud Nijman aff002;  Anda Balode aff003;  Ulrich von Both aff004;  Enitan D. Carrol aff006;  Irini Eleftheriou aff008;  Marieke Emonts aff009;  Michiel van der Flier aff012;  Ronald de Groot aff012;  Jethro Herberg aff002;  Benno Kohlmaier aff015;  Emma Lim aff009;  Ian Maconochie aff016;  Federico Martinon-Torres aff017;  Daan Nieboer aff018;  Marko Pokorn aff019;  Franc Strle aff019;  Maria Tsolia aff008;  Shunmay Yeung aff020;  Dace Zavadska aff003;  Werner Zenz aff015;  Clementien Vermont aff021;  Michael Levin aff002;  Henriette A. Moll aff001
Působiště autorů: Department of General Paediatrics, Erasmus MC–Sophia Children’s Hospital, Rotterdam, The Netherlands aff001;  Section of Paediatric Infectious Disease, Imperial College London, London, United Kingdom aff002;  Department of Paediatrics, Children’s Clinical University Hospital, Rīgas Stradiņa Universitāte, Riga, Latvia aff003;  Division of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig Maximilian University, Munich, Germany aff004;  Partner Site Munich, German Center for Infection Research (DZIF), Munich, Germany aff005;  Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom aff006;  Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom aff007;  Second Department of Paediatrics, P. & A. Kyriakou Children’s Hospital, National and Kapodistrian University of Athens, Athens, Greece aff008;  Paediatric Immunology, Infectious Diseases & Allergy, Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom aff009;  NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, Newcastle upon Tyne, United Kingdom aff010;  Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom aff011;  Paediatric Infectious Diseases and Immunology, Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, the Netherlands aff012;  Section of Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands aff013;  Paediatric Infectious Diseases and Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands aff014;  Department of General Paediatrics, Medical University of Graz, Graz, Austria aff015;  Paediatric Emergency Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom aff016;  Genetics, Vaccines, Infections and Paediatrics Research Group (GENVIP), Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain aff017;  Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands aff018;  Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia aff019;  Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom aff020;  Department of Paediatric Infectious Diseases and Immunology, Erasmus MC–Sophia Children’s Hospital, Rotterdam, the Netherlands aff021
Vyšlo v časopise: Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE): A multicentre observational study. PLoS Med 17(8): e32767. doi:10.1371/journal.pmed.1003208
Kategorie: Research Article



The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe.

Methods and findings

Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country.


In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.

Klíčová slova:

Antibiotics – Bacterial diseases – C-reactive proteins – Critical care and emergency medicine – Fevers – Lower respiratory tract infections – Respiratory infections – Viral transmission and infection


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