Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial

Abstract

Background Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups.Methods ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298).Findings Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1•13 [95% CI 0•90-1•42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis.Interpretation Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.

Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT

“…Several other trials have generated results that complement CAP-IT findings, or are expected to in the near future. In the UK, this includes the primary care-based ARTIC PC (Antibiotics for lower Respiratory Tract Infection in Children presenting in Primary Care) study, 99 a randomised placebo-controlled trial investigating the benefit of a 7-day course of oral amoxicillin in children with possible lower respiratory tract infection (but not considered to have pneumonia clinically). The SAFER (Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia) trial 100 in Canada and SCOUT-CAP (Short Course Outpatient Therapy of Community Acquired Pneumonia) study in the USA both target children presenting to EDs but not admitted to hospital, the former comparing 5-and 10-day treatment courses with amoxicillin and the latter a selection of beta-lactams.…”

Antibiotics for lower respiratory tract infection in children presenting in primary care (ARTIC-PC): the predictive value of molecular testing

“…Overview of methods. The main trial results and methods have been published elsewhere 15 . Where parents and clinicians were willing for children to be randomised, children aged 6 months to 12 years were randomised to receive amoxicillin 50mg/kg/day in three divided doses for 7 days, or placebo, using pre-prepared packs randomised using computer generate random number by an independent statistician.…”

Antibiotic prescribing rate after optimal near-patient C-reactive protein testing in acutely ill children presenting to ambulatory care (ARON project): protocol for a cluster-randomized pragmatic trial

“…Children become ill quite often, mainly because of infections which can be managed in the community in most cases. Children are often prescribed antibiotics (AB) unnecessarily, 1 which contributes to antimicrobial Strengths and limitations of this study ► ARON will be the first pragmatic cluster-randomized controlled superiority trial with nested process evaluation assessing the clinical effectiveness of a diagnostic algorithm on the management of acutely ill children in ambulatory care. ► Linkage with administrative datasets (including data on required hospitalisations, consultations and pharmaceuticals, as well as parental productivity losses) will allow us to identify significant cost drivers and evaluate the cost effectiveness of the intervention.…”

“…25 26 POC CRP testing may also reduce AB prescribing to acutely ill children in ambulatory care. 1 A relatively recent review of the literature showed that using CRP as a POC test reduces AB prescriptions in children if guidance is provided. AB prescriptions by primary care physicians decrease (up to 44%) only if clear instructions on how to interpret the result of the CRP test are provided.…”

“…Children become ill quite often, mainly because of infections which can be managed in the community in most cases. Children are often prescribed antibiotics (AB) unnecessarily, 1 which contributes to antimicrobial resistance, reinforces health-seeking behaviour and unnecessarily increases costs. 2…”