Randomised Controlled Trial of Intravenous Antibiotics on OPAT Versus Hospital for Cellulitis in Children: Comparison of Efficacy, Safety and Antibiotic Resistance

Background The dramatic increase of outpatient parenteral antimicrobial therapy (OPAT) in children, commonly using ceftriaxone, has no trial-based evidence to support it. We aimed to compare the efficacy and safety of treatment with intravenous antibiotics at home versus standard treatment in hospital, in children with moderate/severe cellulitis. Methods In a non-inferiority randomised controlled trial, children aged 6 months-18 years with uncomplicated moderate/severe cellulitis were randomised to receive either intravenous ceftriaxone at home or intravenous flucloxacillin in hospital. Patients were randomised 1:1, stratified by age and presence of periorbital cellulitis. The primary outcome was treatment failure defined as lack of clinical improvement or adverse event, resulting in change of antibiotics within 48 hours. For home treatment to be non-inferior, the difference was designated as less than 15%, with a sample size of 188 providing 80% power. ClinicalTrials.gov: NCT02334124. Results Between 9th January, 2015 and 15th June, 2017, 188 children were randomised, 93 to home treatment and 95 to hospital treatment. In the intention-to-treat population, 2/93 (2%) patients in the home group had treatment failure compared to 7/95 (7%) in the hospital group (risk difference [RD] -5·2%; 95% confidence interval [CI] -11·3 to 0·8, p=0·09). In other words, the results of this non-inferiority randomised trial significantly reject the null hypothesis that home treatment is inferior to hospital treatment. In the per-protocol analysis, the difference was significantly higher in favour of the home group (RD -6·5%; 95% CI -12·4 to -0·7, p=0·03). Adverse events occurred less with home treatment (2% vs 10%, p=0·048) and complications were similar. There was no difference in the rates of acquisition of nasal methicillin-resistant Staphylococcus aureus, or gastrointestinal extended spectrum beta-lactamase-producing bacteria or Clostridium difficile at 3 months after enrolment. Interpretation Home treatment of cellulitis in children with intravenous ceftriaxone is not inferior to treatment in hospital with intravenous flucloxacillin. Intravenous ceftriaxone at home did not show a signal of increased acquisition of resistant bacteria, although larger studies are needed. Trial Registration Number: ClinicalTrials.gov: NCT02334124. Funding: This study was funded in part by grants from the RCH Foundation, the Murdoch Children's Research Institute (MCRI), the Victorian Department of Health, Melbourne Australia. LFI was supported in part by a scholarship from AVANT Mutual Group Ltd, Melbourne, the Melbourne Children’s Campus Postgraduate Health Research Scholarship and the Doctor Nicholas Collins Fellowship. PAB was in part supported by a Melbourne Campus Clinician Scientist Fellowship, Melbourne, Australia. FEB was supported in part by a grant from the RCH Foundation and a Melbourne Campus Clinician Scientist Fellowship, Melbourne, Australia and a National Health and Medical Research Council (NHMRC) Practitioner Fellowship, Canberra, Australia. The emergency research group, MCRI, is in part supported by an NHMRC Centre for Research Excellence Grant for Paediatric Emergency Medicine, Canberra, Australia and the Victorian government infrastructure support program. Declaration of Interest: The authors listed above certify that they have no affiliations with any organisation or entity with any financial or non-financial interest on the materials discussed in this manuscript. The authors declare there are no competing interests of note. Funding organisations had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Ethical Approval: Ethics approval was obtained from the institutional human research and ethics committee. The study protocol was previously published.