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
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 antibiotic...
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| Language: | English |
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NIHR Journals Library
2016-03-01
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| Series: | Health Technology Assessment |
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| Online Access: | https://doi.org/10.3310/hta20190 |
| _version_ | 1818522298150289408 |
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| author | Nick A Francis Matthew J Ridd Emma Thomas-Jones Victoria Shepherd Christopher C Butler Kerenza Hood Chao Huang Katy Addison Mirella Longo Charis Marwick Mandy Wootton Robin Howe Amanda Roberts Mohammed Inaam-ul Haq Vishnu Madhok Frank Sullivan on behalf of the CREAM team |
| author_facet | Nick A Francis Matthew J Ridd Emma Thomas-Jones Victoria Shepherd Christopher C Butler Kerenza Hood Chao Huang Katy Addison Mirella Longo Charis Marwick Mandy Wootton Robin Howe Amanda Roberts Mohammed Inaam-ul Haq Vishnu Madhok Frank Sullivan on behalf of the CREAM team |
| author_sort | Nick A Francis |
| collection | DOAJ |
| description | 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. Design: Multicentre randomised, double-blind, placebo-controlled trial. Setting: General practices and dermatology clinics in England, Wales and Scotland. Participants: Children (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 measures: 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. Trial registration: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420. Funding: The National Institute for Health Research Health Technology Assessment programme. |
| first_indexed | 2024-12-11T05:31:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1366-5278 2046-4924 |
| language | English |
| last_indexed | 2024-12-11T05:31:24Z |
| publishDate | 2016-03-01 |
| publisher | NIHR Journals Library |
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| series | Health Technology Assessment |
| spelling | doaj.art-8dbad8a2d0544d8b966c0a4ccbc190ed2022-12-22T01:19:24ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242016-03-01201910.3310/hta2019009/118/03A 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) studyNick A Francis0Matthew J Ridd1Emma Thomas-Jones2Victoria Shepherd3Christopher C Butler4Kerenza Hood5Chao Huang6Katy Addison7Mirella Longo8Charis Marwick9Mandy Wootton10Robin Howe11Amanda Roberts12Mohammed Inaam-ul Haq13Vishnu Madhok14Frank Sullivan15on behalf of the CREAM teamCochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UKCentre for Academic Primary Care, National Institute for Health Research School of Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol, UKSouth East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UKSouth East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UKCochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UKSouth East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UKSouth East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UKSouth East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UKSwansea Centre for Health Economics, Swansea University, Swansea, UKPopulation Health Sciences, School of Medicine, University of Dundee, Dundee, UKSpecialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital Wales, Cardiff, UKSpecialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital Wales, Cardiff, UKCentre of Evidence Based Dermatology, University of Nottingham, Nottingham, UKSouth East Wales Trials Unit, School of Medicine, Cardiff University, Cardiff, UKPark House Surgery, Surrey, UKDepartment of Family and Community Medicine and Dalla Lana School of Public Health, North York General Hospital University of Toronto, Toronto, ON, CanadaBackground: 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. Design: Multicentre randomised, double-blind, placebo-controlled trial. Setting: General practices and dermatology clinics in England, Wales and Scotland. Participants: Children (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 measures: 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. Trial registration: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420. Funding: The National Institute for Health Research Health Technology Assessment programme.https://doi.org/10.3310/hta20190eczemainfectionstaphylococcus aureusoral antibioticstopical antibioticsrandomised controlled trial |
| spellingShingle | Nick A Francis Matthew J Ridd Emma Thomas-Jones Victoria Shepherd Christopher C Butler Kerenza Hood Chao Huang Katy Addison Mirella Longo Charis Marwick Mandy Wootton Robin Howe Amanda Roberts Mohammed Inaam-ul Haq Vishnu Madhok Frank Sullivan on behalf of the CREAM team 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 Health Technology Assessment eczema infection staphylococcus aureus oral antibiotics topical antibiotics randomised controlled trial |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | eczema infection staphylococcus aureus oral antibiotics topical antibiotics randomised controlled trial |
| url | https://doi.org/10.3310/hta20190 |
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