Title: Patient-tailored antibiotic therapy in acute cellulitis
Funder: Department of Health and Social Care

Abstract: Background Cellulitis is a bacterial skin infection characterised by pain, redness, swelling and fever. The infection frequently recurs and can lead to chronic tissue damage. It is one of the commonest infections leading to hospitalisation, accounting for ~90,000 admissions in England in 2018. The incidence of cellulitis in older populations is increasing as are the associated healthcare costs. Although short treatment durations (5-7 days) are effective for most patients, some need longer to achieve sustained cure. We are currently unable to identify who these patients are, which results in many patients receiving >14 days of treatment (probably more than twice the amount necessary). This accelerates the development of antimicrobial resistance, which is a major threat to global health and is responsible for 33,000 deaths/year in Europe alone. Aim To understand how patient factors, including early clinical response to treatment, can be used to tailor antibiotic treatment duration for cellulitis, giving the best chance of achieving cure while avoiding unnecessary antibiotic exposure. Objectives: To develop a risk score to predict clinical outcome from baseline patient factors based on large-scale electronic health records (EHR). To test this risk score in a prospective cohort of patients with cellulitis and investigate whether early clinical response adds prognostic value. To identify the best technology for measuring skin temperature change as an objective marker of early clinical response. To develop an algorithm to stop antibiotics based on the risk score and clinical response.Methods Retrospective EHR analysis: Data on ~5000 patients identified from an existing database based on diagnostic codes for cellulitis will be used to develop a risk score to predict clinical outcome from baseline factors. Prospective cohort study: Adults with cellulitis receiving antibiotic treatment from a hospital will be eligible. The cohort will be used to test the risk score and investigate whether changes in affected skin temperature or other measures of early clinical response add prognostic value to the risk score. The primary outcome is sustained cure at 90 days. Secondary outcomes include cure at 28 days, patient-reported improvement in symptoms, readmissions, mortality, antibiotic-related adverse events and quality of life. Technology comparison: Three technologies will be used to measure skin temperature change (as an objective marker of early clinical response) in the cohort. The technologies will be compared in terms of repeatability, reproducibility, time and cost to establish the optimal device for measuring clinical response in cellulitis.Anticipated impact My goals are to develop a robust risk score to predict clinical outcome in cellulitis and an algorithm based on this risk score to tailor antibiotic treatment duration for patients with cellulitis. The cohort will provide estimates of the rates of my outcomes to help design a trial to compare this approach to standard of care antibiotic duration. This will enable doctors to make evidence-based, personalised decisions about antibiotic treatment. Reducing unnecessary antibiotic treatment will protect patients from antibiotic-associated adverse events and antibiotic-resistant infections. For the wider healthcare system, this will make delivery of care more efficient and reduce costs for treating cellulitis.

Lay abstract: BackgroundCellulitis is an increasingly common and unpleasant bacterial infection of the skin, usually affecting the legs. Patients experience pain and swelling, loss of mobility, fever and chills. Patients may be left with chronic skin damage and 1 in 5 experience recurrences. In 2018, ~90,000 hospital admissions in England were due to cellulitis. Cellulitis is treated with antibiotics either as tablets or injected into a vein, depending on severity. We know which antibiotics work for treating cellulitis, but we are less clear as to how long treatment should be for. There is good evidence that most patients are cured by just 5 days of treatment, but some need longer to prevent the infection recurring. At the moment doctors don't know how to identify these patients. As a result, many patients get much longer antibiotic treatment than they need. This exposes them to unnecessary risks because taking antibiotics when they are not needed can: Cause side effects (such as diarrhoea, rashes, feeling sick) Kill natural 'good' bacteria in your body that keep you healthy Cause the bacteria that your body carries to become resistant to antibiotics, meaning that common antibiotics don't work anymoreAim(s)I want to find out what features of individual patients predict how likely they are to make a good, sustained recovery from cellulitis. These may include medical conditions a patient already has and how they respond to the first few days of their antibiotic treatment, such as changes in their skin temperature. I will use this information to develop a scoring system and set of rules to guide the length of antibiotic treatment so that patients receive the amount of antibiotics they need and no more. Research methodsThree pieces of research will help me achieve these aims: I will look back at the electronic health records of a large number of patients with cellulitis (~5000). I will use these to create a scoring system to work out who might need longer antibiotic treatment for cellulitis. I will collect more detailed information on a smaller number of patients with cellulitis at the time they are being treated with antibiotics either in or from a hospital. In these patients, I will test my scoring system. I will also measure how they respond to their treatment (e.g. changes in their skin temperature) to see if this information improves my scoring system. I will follow patients up for 3-6 months to see what happens to them including whether their cellulitis returns. I will test how well three new devices work for measuring changes in skin temperature. These results will help me to decide which one is best for measuring response to treatment in cellulitis.Public involvementI have discussed my plans with a patient and public involvement group including four people with an interest in bacterial infections and how technologies could improve their diagnosis and management. They felt that this was a worthwhile research plan that would be acceptable to both patients and carers. Throughout the project I will work with a group of patients that have previously had cellulitis. They will advise me on key parts of the research including the recruitment process, data collection methods, patient information materials and dissemination activities. DisseminationThe results will be shared with the patients involved in the research through a study website. They will also be shared with the public involvement groups working on the research. I will use social media and public engagement events to communicate with the wider public. I will share the results with other healthcare professionals through scientific journals and local, regional, and national/international meetings.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION