Title: Ambulatory Strategies in Pleural Infection.
Funder: Department of Health and Social Care

Abstract: Background Pleural infection affects 15,000 adults in the UK every year. It is characterised by the accumulation of infected fluid within the pleural space, which must be drained for optimal resolution. Currently, patients are admitted to hospital for chest tube insertion and intravenous antibiotics. The average hospital length of stay (LOS) in previous trials was 13 days. Given many patients are stable for much of their admission, there are opportunities for reducing LOS and improving patient experience.There are two significant barriers to hospital discharge in pleural infection;1. Conventional chest tubes require inpatient care for the duration of their insertion.2. Uncertainty about the ability of antibiotics to penetrate the pleural space, so patients often receive protracted intravenous courses.Therapeutic thoracentesis (TT) is an ambulatory alternative to a chest tube, which involves draining the pleural space using a small catheter which is then removed. This can be repeated if fluid reaccumulates, but the patient is able to mobilise or even be discharged between procedures. Case series report the safe use of TT in pleural infection, but no randomised trial data exists.The majority of literature on antibiotic concentrations within the infected pleural space is from rabbit models. There are no studies of current antibiotics' ability to penetrate the infected pleural space in adults. Aims This research will address the necessity of hospital-centric management of pleural infection using 3 workstreams (WS). Methods WS1-Pleural Infection Ambulatory Management Strategies (PIMS) trial This is a single-centre randomised trial in which 30 participants will be allocated to receive chest tube or TT. The trial will recruit for 15 months with 3 months for follow-up. The primary outcome is feasibility (randomisation rate). Secondary outcomes will include number of procedures, hospital LOS, health related quality of life, and patient activity monitoring.WS2-Qualitative study As well as patient and public involvement (PPI) prior to the PIMS trial, afterwards we will perform semi-structured interviews with participants and health professionals. These will focus on their experiences of participating in the trial, to inform the feasibility of a full-scale trial in the future.WS3-Antibiotics concentrations study Pleural fluid samples from WS1 will be analysed to assess the ability of antibiotics to penetrate the pleural space. The concentration of antibiotics will be measured and compared to the minimum inhibitory concentrations of known causative bacteria.Benefits to patients and NHS within 5 years This research aims to improve the current management of pleural infection by addressing some of the current barriers to hospital discharge. This would benefit patients and have clear cost-saving benefits for the health service. Specifically; If successful, the PIMS trial (WS1) will improve current management of pleural infection by demonstrating the utility of an ambulatory approach and helping to design a full-scale trial. The qualitative work (WS2) will provide information on the patient experience of pleural infection, as well helping to design future trials. The antibiotic concentration study (WS3) will inform antibiotic delivery and stewardship, potentially reducing intravenous prescribing and development of resistant organisms.

Lay abstract: Introduction When people get chest infections, fluid can sometimes build up around the lung. This is called a pleural effusion. In about 1 in 10 cases, the fluid itself becomes infected. This is called pleural infection, and affects 15,000 adults in the UK every year.Pleural infection is treated by removing the infected fluid, and using antibiotics to mop up the left-over infection. The most common method of removing the fluid is to insert a chest tube (about 6mm across) through the chest wall, to allow fluid to drain into a collection bottle. This tube stays in until all the fluid has come out, usually between 3-5 days, although it can be much longer. The tube can be sore, and prevents people moving around normally. Patients need to stay in hospital whilst the tube is in position, and whilst receiving intravenous antibiotics. The average hospital stay for pleural infection is 13 days, placing a significant burden on patients, their families, and the health service.An alternative to chest tube drainage is a procedure called therapeutic thoracentesis (TT). This involves inserting a smaller (3mm) tube into the fluid and drawing off as much as possible, over 20 minutes or so, before removing the tube. This can be repeated if the fluid builds up again. This method allows patients to move around freely between procedures and even be managed out of hospital. For this reason, it is called ambulatory management'. However, we do not know whether TT might mean it takes longer for the infection to fully clear. Although some hospitals in Europe use TT for pleural infection, no studies have ever directly compared chest tubes to TT.Aim and methods This research will look at the use of ambulatory management of pleural infection using 3 workstreams (WS);WS1- Test trial of TT in pleural infection (PIMS Trial). We will perform a feasibility trial to assess whether a full-scale trial would be possible, safe and acceptable for patients. Before starting, we will involve people who have had pleural infection to get their input on trial design and processes.In the trial, information will be collected on all patients who are admitted to Southmead hospital with pleural infection. Provided they don't have a particularly complicated pleural infection they will be invited to participate. Thirty participants will be randomly allocated to have either chest tube or TT. Information on hospital stay, participant mobility and quality of life will be collected. However, the main outcome will be whether a full-scale trial would be possible (i.e.were participants willing to take part).WS2- Interviews with patients and health professionals. A trial of ambulatory management will only be feasible if the approach is acceptable to patients and health professionals. After the trial, we will interview the patients, doctors and nurses who participated, about their experiences, and whether they feel a larger trial would be possible.WS3- Antibiotic concentrations in pleural fluid. Patients with pleural infection often receive long courses of intravenous antibiotics because doctors are uncertain of how well antibiotics reach the infected pleural fluid. To answer this, we will collect samples of pleural fluid from participants who take part in WS1. This fluid will be tested to measure how much antibiotic has managed to get into it. We can then tell if the antibiotics are reaching high enough concentrations to kill bacteria. This information may shorten the time patients are treated with intravenous antibiotics.Dissemination We will present the results to patient-support groups and publish them in the British Lung Foundation patient newsletter. The final write-up will be submitted to peer-reviewed medical journals and presented at conferences.

Research activity codes: 6.3 MEDICAL DEVICES;6.4 SURGERY
Health categories: INFECTION