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Background: Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here., Methods/design: Patients will be randomised to either orally administered flucloxacillin 500 mg four times daily and placebo or orally administered 500 mg of flucloxacillin four times daily and phenoxymethylpenicillin 500 mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper., Discussion: This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin/phenoxymethylpenicillin dual therapy for the ED-directed outpatient treatment of cellulitis. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines. The SAP for the PEDOCELL trial was developed a priori in order to minimise analysis bias., Trial Registration: EU Clinical Trials Register (EudraCT number: 2016-001528-69). Registered on 5 April 2016. ClinicalTrials.gov, ID: NCT02922686 . Registered on 9 August 2016.

Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The objectives of this systematic review and meta-analysis were to identify and appraise all controlled observational studies that have examined risk factors for the development of nonpurulent cellulitis of the leg (NPLC). A systematic literature search of electronic databases and grey literature sources was performed in July 2015. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality of included studies. Of 3059 potentially eligible studies retrieved and screened, six case-control studies were included. An increased risk of developing NPLC was associated with previous cellulitis [odds ratio (OR) 40·3, 95% confidence interval (CI) 22·6-72·0], wound (OR 19·1, 95% CI 9·1-40·0), current leg ulcers (OR 13·7, 95% CI 7·9-23·6), lymphoedema/chronic leg oedema (OR 6·8, 95% CI 3·5-13·3), excoriating skin diseases (OR 4·4, 95% CI 2·7-7·1), tinea pedis (OR 3·2, 95% CI 1·9-5·3) and body mass index > 30 kg m -2 (OR 2·4, 95% CI 1·4-4·0). Diabetes, smoking and alcohol consumption were not associated with NPLC. Although diabetics may have been underrepresented in the included studies, local risk factors appear to play a more significant role in the development of NPLC than do systemic risk factors. Clinicians should consider the treatment of modifiable risk factors including leg oedema, wounds, ulcers, areas of skin breakdown and toe-web intertrigo while administering antibiotic treatment for NPLC., (© 2016 British Association of Dermatologists.)

Objectives: There is a lack of evidence to guide the management of cellulitis in the emergency department (ED). The primary aim of this study was to characterize antibiotic-prescribing practices for the treatment of cellulitis in Irish EDs. Secondary aims were to identify patient variables associated with the prescription of intravenous (i.v.) antibiotics and to describe the utility of three published guidelines for the management of cellulitis in the ED., Methods: This was a multicentre, prospective, observational cross-sectional study of consecutive patients presenting to six EDs in Ireland over a 1-month period (June 2012)., Results: In total, 117 patients were enrolled. Fifty-five percent of all patients (n=65) were referred from primary care, and emergency physicians prescribed i.v. therapy in 50% of patients (n=59) overall. Nonpurulent cellulitis accounted for 96.5% of cases (n=113). Flucloxacillin, either alone or with penicillin V, is the most commonly prescribed oral antibiotic in patients both referred from primary care and discharged from the ED. Flucloxacillin with benzylpenicillin is the most commonly prescribed i.v., Treatment: Fever, increasing diameter of infection, and tinea pedis were associated with prescription of i.v. antibiotics by emergency physicians. The three guidelines examined in this study recommended oral antibiotic treatment for between 33-44% of patients who were treated with i.v. antibiotics by emergency physicians., Conclusion: In Ireland, current prescribing practices for CREST 1 and modified CREST 1 and 2 patients are poorly adherent to guideline recommendations.

Introduction: Assessment of cellulitis severity in the emergency department (ED) setting is problematic. Given the lack of research performed to describe the epidemiology and management of cellulitis, it is unsurprising that heterogeneous antibiotic prescribing and poor adherence to guidelines is common. It has been shown that up to 20.5% of ED patients with cellulitis require either a change in route or dose of the initially prescribed antibiotic regimen. The current treatment failure rate for empirically prescribed oral antibiotic therapy in Irish EDs is unknown. The association of patient risk factors with treatment failure has not been described in our setting. Lower prevalence of community-acquired methicillin-resistant Staphylococcus aureus-associated infection, differing antibiotic prescribing preferences and varying availability of outpatient intravenous therapy programmes may result in different rates of empiric antibiotic treatment failure from those previously described., Methods and Analysis: Consecutive ED patients with cellulitis will be enrolled on a 24/7 basis from 3 Irish EDs. A prespecified set of clinical variables will be measured on each patient discharged on empiric oral antibiotic therapy. A second independent study recruiter will assess at least 10% of cases for each of the predictor variables. Follow-up by telephone call will occur at 14 days for all discharged patients where measurement of the primary outcome will occur. Our primary outcome is treatment failure, defined as a change in route of antibiotic administration from oral to intravenous antibiotic. Our secondary outcome is change in dose or type of prescribed antibiotic. A cohort of approximately 152 patients is required to estimate the proportion of patients failing oral antibiotic treatment with a margin of error of 0.05 around the estimate., Ethics and Dissemination: Full ethics approval has been granted. An integrated dissemination plan, involving diverse clinical specialties and enrolled patients, is described., Trial Registration Number: NCT 02230813., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

To characterise the Emergency Department (ED) prevalence of cellulitis, factors predicting oral antibiotic therapy and the utility of the Clinical Resource Efficiency Support Team (CREST) guideline in predicting patient management in the ED setting, a prospective, cross-sectional study of consecutive adult patients presenting to 3 Irish EDs was performed. The overall prevalence of cellulitis was 12 per 1,000 ED visits. Of 59 patients enrolled, 45.8% were discharged. Predictors of treatment with oral antibiotics were: CREST, Class 1 allocation (odds ratio (OR) 6.81, 95% Cl =1.5-30.1, p=0.012), patient self-referral (OR= 6.2, 95% Cl 1.9- 20.0, p=0.03) and symptom duration longer than 48 hours (OR 1.2, 95% Cl = 1.0-1.5,p=0.049). In conflict with guideline recommendation, 43% of patients in CREST Class 1 received IV therapy. Treatment with oral antibiotics was predicted by CREST Class 1 allocation, self-referral, symptom duration of more than 48 hours and absence of pre-EO antibiotic therapy.

Background: Flucloxacillin either alone or combined with penicillin V is still the first-line antibiotic drug of choice for the treatment of cellulitis in emergency departments (EDs) in Ireland. The rationale for this antibiotic regimen is their anti-staphylococcal and anti-streptococcal activity., Objective: To determine the clinical efficacy, tolerability and safety of oral flucloxacillin alone (monotherapy) compared with a combination of flucloxacillin with penicillin V (dual therapy) in the ED-directed outpatient treatment of cellulitis., Methods: We searched the following electronic databases: MEDLINE (1950 to August 2011), EMBASE (1980 to August 2011), Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue), OpenGrey, Current Controlled Trials metaRegister of Clinical Trials (August 2011) and reference lists and websites of potential trials. We performed cross-referencing from the reference lists of major articles on the subject. We imposed no language restriction., Results: Despite a comprehensive literature search to identify relevant studies, no randomized-controlled trials that fulfilled the inclusion criteria were found., Conclusions: Despite its common use, there are no published randomized-controlled trials comparing flucloxacillin monotherapy with a combination of flucloxacillin and penicillin V in the ED management of cellulitis. We discuss existing European and North American prescribing rationale and current guidelines.

Background: Oral flucloxacillin, either alone or in combination with phenoxymethylpenicillin, is a commonly prescribed antibiotic for the treatment of cellulitis, particularly in Ireland and the United Kingdom. This study aims to establish the non-inferiority of oral monotherapy (flucloxacillin alone) to dual therapy (flucloxacillin and phenoxymethylpenicillin) for the outpatient treatment of cellulitis in adults., Methods/design: This study is a multicentre, randomised, double-blind, placebo-controlled trial of adults who present to the emergency department (ED) with cellulitis that is deemed treatable on an outpatient basis with oral antibiotics. After fulfilling specified inclusion and exclusion criteria, informed consent will be taken. Patients will be given a treatment pack containing 7 days of treatment with flucloxacillin 500 mg four times daily and placebo or flucloxacillin 500 mg four times daily and phenoxymethylpenicillin 500 mg four times daily. The primary outcome measure under study is the proportion of patients in each group in which there is greater than or equal to a 50% reduction in the area of diameter of infection from the area measured at enrolment at the end-of-treatment visit (7 to 10 days). Secondary endpoints include a health-related quality of life measurement as rated by the SF-36 score and the Extremity Soft Tissue Infection Score (not validated), compliance and adverse events. Patients will be followed up by telephone call at 3 days, end-of-treatment visit (EOT) at 7 to 10 days and test-of-cure (TOC) visit at 30 days. To achieve 90% power, a sample size of 172 patients per treatment arm is needed. This assumes a treatment success rate of 85% with oral flucloxacillin and phenoxymethylpenicillin, an equivalence threshold Δ = 12.5% and an α = 0.025. Non-inferiority will be assessed using a one-sided confidence interval on the difference of proportions between the two groups. Standard analysis including per-protocol and intention-to-treat will be performed., Discussion: This trial aims to establish the non-inferiority of flucloxacillin monotherapy to dual therapy in the treatment of uncomplicated cellulitis among ED patients. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines.