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

• Published in: PLoS medicine 2020-01, Vol.17 (1), p.e1003034-e1003034
• Main Authors: van de Maat, Josephine S, Peeters, Daphne, Nieboer, Daan, van Wermeskerken, Anne-Marie, Smit, Frank J, Noordzij, Jeroen G, Tramper-Stranders, Gerdien, Driessen, Gertjan J A, Obihara, Charlie C, Punt, Jeanine, van der Lei, Johan, Polinder, Suzanne, Moll, Henriette A, Oostenbrink, Rianne
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - standards; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antimicrobial Stewardship - methods; Antimicrobial Stewardship - standards; Bacterial infections; Biology and Life Sciences; Biomarkers; C-reactive protein; Child, Preschool; Children; Clinical Decision Rules; Clinical medicine; Cluster Analysis; Consent; Cough; Drug Prescriptions - standards; Dyspnea; Emergency medical care; Empyema; Female; Fever; Funding; Hospitals; Humans; Infant; Male; Medicine and Health Sciences; Netherlands - epidemiology; Pediatrics; People and Places; Physical Sciences; Pneumonia; Prediction models; Public health; Research and Analysis Methods; Respiration; Respiratory tract diseases; Respiratory tract infection; Respiratory Tract Infections - diagnosis; Respiratory Tract Infections - drug therapy; Respiratory Tract Infections - epidemiology; Risk groups
• ISSN: 1549-1676; 1549-1277; 1549-1676
• 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. 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), result