The Ambulatory Management of Pleural Infection

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Introduction
Pleural infection is a serious condition with a considerable healthcare burden given the potential requirement of chest tube drainage, intrapleural fibrinolytics or thoracic surgery. The current management strategy defaults to extended hospital admissions. This thesis evaluates the current barriers to the ambulatory management of pleural infection using mixed methodologies at different stages of the care pathway.

Methods
To establish the population at risk, the burden of pleural infection in England was assessed using validated Hospital Episode Statistics (HES) and a prospective multicentre cohort study.
To enable early decision making around management a pleural fluid biomarker, soluble urokinase Plasminogen Activator Receptor (suPAR), was investigated in a prospective cohort study.
An alternative to chest tube insertion (therapeutic thoracentesis) was assessed in a feasibility randomised controlled trial which might reduce the need for hospital admission.
Finally, a pharmacokinetic study was designed to address the uncertainty around antibiotic penetration into the pleural space that often leads to extend courses of intravenous antibiotics.

Results
HES data demonstrated that the incidence of pleural infection is increasing year on year with ‘surges’ in the winter months. These surges have been temporally linked to influenza spikes with confirmatory serological data from a prospective cohort analysis.
Pleural fluid suPAR was able to predict the need for medical/surgical rescue therapies compared to conventional markers which would allow earlier management decisions.
The feasibility randomised trial of therapeutic thoracentesis versus chest tube insertion met its pre-specified criteria on patient acceptability (91% accepting randomisation) but under-recruited for various reasons including the COVID-19 pandemic, patients being unable to consent, and complex effusions.
The preliminary results of antibiotic concentrations within the pleural space suggest that penetration is generally good with the possibility of early oral antibiotic courses to reduce the dependence on intravenous administration.

Conclusion
Pleural infection is becoming increasingly common but management defaults to extended hospital admissions. This thesis has addressed several barriers to a more ambulatory approach through improved diagnostics, a better understanding of pleural antibiotic pharmacokinetics, and developing the platform for a future randomised trial of a more ambulatory approach.
Date of Award25 Jan 2022
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorNick A Maskell (Supervisor) & Andrew J Moore (Supervisor)

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