Cellulitis Optimal Antibiotic Treatment: COAT study

Research question: Is a short course (5d) of flucloxacillin non-inferior to a standard course (7d) in terms of pain over days 6-14, in patients with leg cellulitis in primary care? Background: Cellulitis is a common, and potentially serious, deep skin infection. It is particularly common in older people, and most commonly occurs in the legs. NICE recommend 5-7 days of the oral antibiotic flucloxacillin for most patients managed in primary care, but over 90% of patients are treated for 7 days or more. Shorter courses of antibiotics have been shown to be as effective as longer courses for many infections and have the potential to reduce adverse effects and the development of antimicrobial resistance. A small number of studies suggest that short courses are as effective as longer courses for cellulitis, but there have been no trials of short courses of oral flucloxacillin for cellulitis. Aims and objectives: 1. Assess the effectiveness and safety of 5 days vs 7 days of flucloxacillin for lower leg cellulitis. 2. Evaluate the cost-consequences of a shorter course from an NHS and personal perspective. Methods: A blinded, non-inferiority trial comparing 5 vs 7 days of flucloxacillin. Participants will be adults presenting in primary care with unilateral leg cellulitis associated with a pain score of 3 or more. Participants will be prescribed flucloxacillin 500mg four times a day (QDS) for 5 days and sent a blinded study pack containing placebo QDS for 2 days (total 5d antibiotic) or flucloxacillin 500mg QDS for 2 days (total 7d antibiotic). Following baseline data collection participants will be asked to rate pain and how unwell they feel using numeric rating scores (0-10), complete EQ-5D, and report antibiotic and analgesic use daily for 14 days using a simple online form and daily SMS links (or paper diary) supported by phone calls. Additional questions on days 7, 14, 21 and 28 will include DLQI, leg tenderness and swelling, use of additional antibiotics, day extent of cellulitis starts to reduce, and day recovered. D28 questions will also include complications, healthcare consultations and costs. Recurrent episodes and long-term complications will be assessed by searching their GP record after 12 months. The primary outcome of pain over days 6-14 will be assessed using repeated measures and the between group difference compared to a non-inferiority margin of 1. Secondary outcomes include recurrent symptoms requiring additional antibiotics, feeling unwell, EQ5D, mobility, self-care, recovery complications and recurrence. Economic effects will be explored by a cost-consequences analysis over the 12-month horizon. Timelines for delivery: Setup: m1-9 Internal pilot: m10-15 Participant recruitment: m10-29 28d follow-up complete: m30 28d follow-up analysis: m32-37 12m follow-up note searches: m30-42 Final analysis and dissemination: m43-48 Anticipated impact and dissemination: The results will inform the management of leg cellulitis in primary care and either support or reject a change to use of a 5-day course of flucloxacillin as standard treatment. If our findings support a change then this will lead to a meaningful reduction in overall antibiotic use, leading to reduced antimicrobial resistance and therefore benefit for patients. Evidence that 5-days is inferior will lead to increased certainty, changes to NICE guidance, and a change in treatment for the minority who currently receive a 5-day course.