A small catheter inserted into the chest and then immediately removed could cut a patient’s hospital stay for pleural infection nearly in half, compared to the standard chest tube that stays in place for days. Pleural infection—when fluid around the lungs becomes infected—currently keeps patients in hospital for a median of two weeks, largely because guidelines default to inserting a permanent chest tube and giving prolonged intravenous antibiotics. No randomised trial has ever tested whether a simpler approach works as well. This trial will recruit 171 patients across 12 UK hospitals to compare therapeutic thoracentesis (repeated short drainage procedures) against the standard chest tube, aiming to detect a 40% reduction in hospital stay (8 versus 13 days). If the approach succeeds, it could shift treatment from hospital-centric care to a model where patients mobilise or go home between procedures, reducing bed occupancy and antibiotic use. A parallel mechanistic workstream will analyse antibiotic levels in drained pleural fluid to determine whether oral antibiotics can replace intravenous ones, and how drainage technique affects drug penetration—answers that could further shorten stays and curb broad-spectrum antibiotic overuse.
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Background: Parapneumonic pleural effusions develop in up to 50% of patients with pneumonia. The majority will resolve with antibiotic treatment of the underlying infection. However, 10% will progress to pleural infection where the pleural fluid itself becomes infected requiring pleural fluid drainage. Guidelines recommend that patients with pleural infection are admitted to hospital for chest tube insertion and intravenous antibiotics. The current median hospital length of stay is 14 days with extended use of broad-spectrum intravenous antibiotics. There are no prospective randomised trials supporting this practice. The major barriers to reducing the hospital-centric management are (i) default to chest tube insertion which limits patients’ mobility and recovery over more conservative approaches (ii) uncertainty about the penetration of antibiotics into the infected fluid leading to a reliance on extended intravenous antibiotic courses. Therapeutic thoracentesis (TT) is an 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. During my NIHR Doctoral Research Fellowship (DRF) I completed the first randomised trial comparing chest tube drainage to TT (n=10). The focus was demonstrating feasibility of recruitment and pilot proof of the protocol (both demonstrated), and secondary analysis showed hospital length of stay was reduced by 50% in the TT group. As effective antibiotic therapy is required for successful resolution of the infected pleural fluid it is vital to understand how drainage technique and antibiotic choice (drug/route/duration) impacts antibiotic pharmacokinetics/pharmacodynamics (PK/PD) . Aim: To test whether TT can reduce the hospital length of stay for patients with pleural infection and how antibiotic PK/PD is impacted, or can be optimised. Methods: During this Efficacy and Mechanism (EME) Programme Advanced Fellowship I will run a full-scale clinical trial comparing chest tube drainage to TT. The Initial Management of Pleural infection: Aspiration versus Chest Tube (IMPACT) trial will recruit 171 patients from 12 UK hospitals over 30 months. This sample size will detect a 40% reduction in hospital length of stay from the intervention (8 vs 13 days), 90% power, alpha 0.05. This would represent a clinically important reduction that would alter current treatment paradigms. To address the uncertainties around antibiotic PK/PD I have embedded a mechanistic workstream within the IMPACT trial. The pleural fluid drained from the TT and chest tubes from trial participants will be collected and correlated with antibiotic treatment. This will be analysed to address the PK/PD of antibiotics in the pleural fluid using techniques developed during my NIHR DRF. By performing this during a trial it will provide a real-world assessment of which antibiotics should be used, whether oral antibiotics are equivalent to intravenous, and how drainage strategy affects antibiotic PK/PD. Impact and dissemination: Both the clinical and mechanistic workstreams have the potential to generate practice changing findings that reduce the burden of pleural infection. I will publish results in medical journals and co-develop infographics that summarise the results for participants, charities, and the public.
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