title: A randomised placebo-controlled trial of oral and topical antibiotics for children with clinically infected eczema in the community: the ChildRen with Eczema, Antibiotic Management (CREAM) study.
abstract: BACKGROUND
  Secondary skin infection is common during eczema exacerbations and many children are treated with antibiotics when this is suspected, although there is little high-quality evidence to justify this practice.
  
  
  OBJECTIVE
  To determine the clinical effectiveness of oral and topical antibiotics, in addition to standard treatment with emollients and topical corticosteroids, in children with clinically infected eczema.
  
  
  METHODS
  Multicentre randomised, double-blind, placebo-controlled trial.
  
  
  METHODS
  General practices and dermatology clinics in England, Wales and Scotland.
  
  
  METHODS
  Children (aged 3 months to < 8 years) with a diagnosis of eczema (according to U.K. Working Party definition) and clinical suspicion of infection.
  
  
  METHODS
  (1) Oral flucloxacillin and topical placebo; (2) topical fusidic acid (Fucidin(®), Leo Laboratories Limited) and oral placebo; and (3) oral and topical placebos, all for 1 week.
  
  
  METHODS
  Patient-Orientated Eczema Measure (POEM) at 2 weeks (assessing subjective severity in the week following treatment).
  
  
  RESULTS
  We randomised 113 children (36 to oral antibiotic, 37 to topical antibiotic and 40 to placebo), which was fewer than our revised target sample size of 282. A total of 103 (92.0%) children had one or more clinical features suggestive of infection and 78 (69.6%) children had Staphylococcus aureus cultured from a skin swab. Oral and topical antibiotics resulted in a 1.52 [95% confidence interval (CI) -1.35 to 4.40] and 1.49 (95% CI -1.55 to 4.53) increase (worse subjective severity) in POEM score at 2 weeks, relative to placebo and controlling for baseline POEM score. Eczema Area and Severity Index (objective severity) scores were also higher (worse) in the intervention groups, at 0.20 (95% CI -0.12 to 0.52) and 0.42 (95% CI 0.09 to 0.75) for oral and topical antibiotics, respectively, at 2 weeks. Analyses of impact on the family, quality of life, daily symptom scores, and longer-term outcomes were all consistent with the finding of no or limited difference and a trend towards worse outcomes in the intervention groups. Sensitivity analyses, including adjusting for compliance and imputation for missing data, were consistent with the main findings.
  
  
  CONCLUSIONS
  Our data suggest that oral and topical antibiotics have no effect, or a harmful effect, on subjective eczema severity in children with clinically infected eczema in the community. The CIs around our estimates exclude a meaningful beneficial effect (published minimal clinically important difference for POEM is 3.4). Although most patients in this trial had features suggestive of infection and S. aureus on their skin, participants primarily had mild-moderate eczema and those with signs of more severe infection were often excluded. Clinicians should consider avoiding oral and topical antibiotic use in children with suspected infected eczema in the community who do not have signs of 'severe infection'. Further research should seek to understand how best to encourage the use of topical steroids and limit use of antibiotics in those with eczema flares without signs of severe infection, as well as developing tools to better phenotype eczema flares, in order to better define a population that may benefit from antibiotic treatment.
  
  
  BACKGROUND
  European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Nick A
authors.initials: NA
authors.lastname: Francis
authors.affiliation: Centre for Academic Primary Care, National Institute for Health Research School of Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ridd
authors.affiliation: South East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Thomas-Jones
authors.affiliation: South East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Shepherd
authors.affiliation: Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK.|Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Butler
authors.affiliation: South East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Kerenza
authors.initials: K
authors.lastname: Hood
authors.affiliation: South East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: South East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Katy
authors.initials: K
authors.lastname: Addison
authors.affiliation: Swansea Centre for Health Economics, Swansea University, Swansea, UK.
authors.forename: Mirella
authors.initials: M
authors.lastname: Longo
authors.affiliation: Population Health Sciences, School of Medicine, University of Dundee, Dundee, UK.
authors.forename: Charis
authors.initials: C
authors.lastname: Marwick
authors.affiliation: Specialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital Wales, Cardiff, UK.
authors.forename: Mandy
authors.initials: M
authors.lastname: Wootton
authors.affiliation: Specialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital Wales, Cardiff, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Howe
authors.affiliation: Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Roberts
authors.affiliation: South East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Mohammed Inaam-ul
authors.initials: MI
authors.lastname: Haq
authors.affiliation: Park House Surgery, Surrey, UK.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Madhok
authors.affiliation: Department of Family and Community Medicine and Dalla Lana School of Public Health, North York General Hospital University of Toronto, Toronto, ON, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Sullivan
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D004485:Eczema / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D011788:Quality of Life; D012720:Severity of Illness Index; D006113:United Kingdom
chemical_list: D000900:Anti-Bacterial Agents