Author Identifier

Estee Lau's ORCID record ORCID Logo

Date of Award

2026

Keywords

pleural infection, empyema, tPA, DNase, indwelling pleural catheter

Document Type

Thesis

Publisher

Edith Cowan University

Degree Name

Doctor of Philosophy

School

School of Medical and Health Sciences

First Supervisor

Carolyn McIntyre ORCID iD 0000-0001-9913-4022

Second Supervisor

Y C Gary Lee ORCID iD 0000-0002-0036-511X

Third Supervisor

Natalia Popowicz

Abstract

Introduction: Pleural infection remains a major clinical concern, with an increasing incidence worldwide. The use of intrapleural tissue plasminogen activator (tPA) with deoxyribonuclease (DNase) therapy represents a major breakthrough as it offers an effective alternative to surgery for patients who fail conventional treatment. However, the optimal dosage of tPA is yet to be established. Indwelling pleural catheter (IPC)-related infections, especially IPC-related pleural infections are a significant concern and a barrier to the uptake of IPC. The development of a long-term preventative strategy is imperative to promote uptake and improve the quality of life of patients, particularly in those who have limited life expectancy.

Aims: This thesis aims to address two primary objectives.

Part 1: Optimising the dosage of intrapleural tPA (with DNase) therapy for pleural infection

To establish the efficacy and safety of a dosing strategy using a lower starting intrapleural dose of 1mg tPA, with dose-escalation as necessary for pleural infection.

Part 2: Addressing concerns associated with IPC-related infections using a long-term topical antibacterial preventative strategy

To assess the impact of mupirocin application on the structural integrity of IPC.

To establish the feasibility of mupirocin exit-site application in patients with an indwelling pleural/peritoneal catheter.

To develop the study protocol for the first randomised controlled trial to evaluate the efficacy of mupirocin prophylaxis in patients with an IPC for malignant pleural effusion (MPE).

Results: Part 1: The Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) study-3 was an observational cohort study including consecutive 100 patients who required intrapleural tPA/DNase therapy whom all received a starting dose of 1mg tPA, with dose-escalation as needed. This dosing strategy successfully treated 94% of patients with a favourable safety profile, demonstrating that lower tPA doses may achieve similar efficacy while facilitating an individualised management.

Part 2: The Topical Antibiotic Prophylaxis for Infections of indwelling Pleural/peritoneal Catheters (TAP-IPC) study was the first pilot feasibility study to investigate the use of mupirocin prophylaxis in patients with an IPC/IPeC (n=50) for malignant effusions. Mupirocin did not alter the structural integrity of the IPC, and its application was feasible and well-tolerated in this patient population. The findings from this study provided the platform for the design of a randomised trial to evaluate its efficacy.

The Australasian Malignant PLeural Effusion (AMPLE)-4 study protocol describes the first randomised trial, currently underway, to evaluate if mupirocin prophylaxis reduces IPC-related infections in patients with an IPC for MPE. The primary outcome is the percentage of patients who develop an IPC-related infection, employing standardised definitions. Secondary outcomes include analyses of infection (types, episodes, microbiology), length of stay, resource utilisation, adverse events and survival. This study is crucial for enhancing our understanding of IPC-related infections and will provide valuable information towards the development of a long-term preventative strategy.

Conclusion: Pleural infection remains an area of many unmet needs. The studies presented in this thesis have contributed new information to the existing knowledge gap by demonstrating the efficacy of a very low starting dose of tPA for managing pleural infection and represent the first effort towards finding a long-term preventative strategy for IPC-related infections, which will provide the foundation for further research.

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Link to publisher version (DOI)

10.25958/zw7p-hd64