Injections using hypodermic needles cause pain, discomfort, localised trauma and apprehension. Additionally, careful use and disposal of needles is required to avoid transmission of blood-borne pathogens. As an alternative, microneedles can facilitate drug delivery without significantly impacting on pain receptors or blood vessels that reside beneath the skin outer layers. In this study we aim to determine the pain and sensory response to the application of wet-etch silicon microneedles, when used in such a way as to reliably penetrate skin, and provide a preliminary indication of how skin responds to microneedle injury with time. Twelve subjects received single-blinded insertions of a 25-G hypodermic needle and two microneedle arrays (36 needles of 180 and 280 mum height). The optimal method for microneedle application was determined in a pilot study. Pain intensity was scored using a visual analogue scale (VAS) and sensory perception determined using an adapted McGill Pain Questionnaire Short Form. Skin penetration was determined by external staining and measurement of trans-epidermal water loss (TEWL). Mean VAS scores, verbal descriptions and questionnaire responses showed that the 180 and 280 mum microneedles caused significantly less pain and discomforting sensation in participants than the hypodermic needle. Methylene blue staining and TEWL analysis confirmed that microchannels were formed in the skin following microneedle application. Evidence of microchannel repair and resealing was apparent at 8-24 h post-application. In summary, this study shows that pyramidal wet-etch microneedles can penetrate human skin with minimal pain and sensory discomfort, creating transient pathways for potential drug, vaccine and DNA delivery.

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.