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

BackgroundSecondary 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.ObjectiveTo 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.DesignMulticentre randomised, double-blind, placebo-controlled trial.SettingGeneral practices and dermatology clinics in England, Wales and Scotland.ParticipantsChildren (aged 3 months to < 8 years) with a diagnosis of eczema (according to U.K. Working Party definition) and clinical suspicion of infection.Interventions(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.Main outcome measuresPatient-Orientated Eczema Measure (POEM) at 2 weeks (assessing subjective severity in the week following treatment).ResultsWe 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 hadStaphylococcus aureuscultured 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.ConclusionsOur 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 andS. aureuson 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.Trial registrationEuropean Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420.FundingThe National Institute for Health Research Health Technology Assessment programme.

Oral and Topical Antibiotics for Clinically Infected Eczema in Children: A Pragmatic Randomized Controlled Trial in Ambulatory Care

“…Participating sites were slightly larger than non-participating practices (mean practice list size 9,452 vs 6,451), but there were no significant differences in number of partners, proportion of list aged 8 years or less, or proportion of children aged 8 years or less who have eczema. 22 One hundred thirteen participants were randomized (Supplemental Appendix 5, available at http://www. AnnFamMed.org/content/15/2/124/suppl/DC1/), which was less than the target sample size.…”

Understanding economic evidence for the prevention and treatment of atopic eczema

“…Francis et al . tested the construct and face validity of the ADQoL completed by parents of children with eczema vs. the clinical measures Patient Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI) and Infants’ Dermatitis Quality of Life Index (IDQoL) . This study supported the use of ADQoL but noted that parents of the youngest participants found it harder to complete.…”

“…Moisturizers or barrier creams were evaluated in six studies . Other preparations evaluated included fluticasone propionate ointment; topical prednicarbate; and some oral preparations, including montelukast, bacterial lysate, ciclosporin A and antibiotics (vs. an antibiotic cream) for infected eczema . Homeopathic interventions were evaluated in three studies .…”

“…Six studies that just considered outcomes were identified . These studies may help to inform the design of future economic evaluations or to parameterize economic models.…”

“…ADQoL has been used in few trial evaluations, although the estimates in the paper have been more widely used in economic modelling studies. Only three trial‐based full‐ or feasibility‐stage economic evaluations in this review used the ADQoL descriptive system to elicit a health state description for each participant . Francis et al .…”