Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial

Autoři: Josephine S. van de Maat aff001;  Daphne Peeters aff002;  Daan Nieboer aff003;  Anne-Marie van Wermeskerken aff004;  Frank J. Smit aff005;  Jeroen G. Noordzij aff006;  Gerdien Tramper-Stranders aff007;  Gertjan J. A. Driessen aff002;  Charlie C. Obihara aff008;  Jeanine Punt aff009;  Johan van der Lei aff010;  Suzanne Polinder aff003;  Henriette A. Moll aff001;  Rianne Oostenbrink aff001
Působiště autorů: Department of General Paediatrics, Erasmus MC–Sophia Children’s Hospital, Rotterdam, The Netherlands aff001;  Department of Paediatrics, HAGA–Juliana Children’s Hospital, Den Haag, The Netherlands aff002;  Department of Public Health, Erasmus MC, Rotterdam, The Netherlands aff003;  Department of Paediatrics, Flevoziekenhuis, Almere, The Netherlands aff004;  Department of Paediatrics, Maasstad Ziekenhuis, Rotterdam, The Netherlands aff005;  Department of Paediatrics, Reinier de Graaf Gasthuis, Delft, The Netherlands aff006;  Department of Paediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands aff007;  Department of Paediatrics, Elisabeth–TweeSteden Ziekenhuis, Tilburg, The Netherlands aff008;  Department of Paediatrics, LangeLand Ziekenhuis, Zoetermeer, The Netherlands aff009;  Department of Medical Informatics, Erasmus MC, Rotterdam, The Netherlands aff010
Vyšlo v časopise: Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial. PLoS Med 17(1): e32767. doi:10.1371/journal.pmed.1003034
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003034



Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule.

Methods and findings

In a stepped-wedge cluster randomised trial, we included children aged 1–60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently (p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study.


In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule.

Trial registration

Netherlands Trial Register NTR5326.

Klíčová slova:

Antibiotics – Critical care and emergency medicine – Fevers – Forecasting – Netherlands – Oxygen – Physicians – Bacterial pneumonia


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