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Introduction Care home residents are at increased risk of infections and antibiotic prescription. Reduced antibiotic use from fewer infections would improve quality of life. The Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS) trial aims to determine the efficacy and investigate mechanisms of daily probiotics on antibiotic use and incidence of infections in care home residents. Methods and analysis PRINCESS is a double-blind, individually randomised, placebo-controlled trial that will assess the effect of a daily oral probiotic combination of Lactobacillus rhamnosus, GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) on cumulative antibiotic administration days (CAADs) (primary outcome) for infection in up to 330 care home residents aged ≥65 years over up to 12 months. Secondary outcomes include: Infection: Total number of days of antibiotic administration for each infection type (respiratory tract infection, urinary tract infection, gastrointestinal infection, unexplained fever and other); number, site, duration of infection; estimation of incidence and duration of diarrhoea and antibioticassociated diarrhoea; Stool microbiology: Clostridium difficile infection; Gram-negative Enterobacteriaceae and vancomycin-resistant enterococci; LGG and BB-12. Oral microbiology: Candida spp. Health and well-being: Self and/or proxy health-related quality of life EQ5D (5 L); selfand/ or proxy-reported ICEpop CAPability measure for older people. Hospitalisations: number and duration of all-cause hospital stays. Mortality: deaths. Mechanistic immunology outcomes: influenza vaccine efficacy (haemagglutination inhibition assay and antibody titres); full blood count and immune cell phenotypes, plasma cytokines and chemokines; cytokine and chemokine response in whole blood stimulated ex vivo by toll-like receptor 2 and 4 agonists; monocyte and neutrophil phagocytosis of Escherichia coli; serum vitamin D. Ethics and dissemination Ethics approval is from the Wales Research Ethics Committee 3. Findings will be disseminated through peer-reviewed journals and conferences; results will be of interest to patient and policy stakeholders. [ABSTRACT FROM AUTHOR]

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.