Exploring Bacteriophage Therapy Against Pseudomonas aeruginosa in Paediatric Cystic Fibrosis: Early-Phase Clinical Trial Implementation

Abstract

This thesis investigates bacteriophage therapy as a treatment for Pseudomonas aeruginosa infections in children with cystic fibrosis (CF). Despite significant advances in CF, P. aeruginosa remains an important pathogen, especially during pulmonary exacerbations, where it contributes to significant lung function decline. In a study of CF children with exacerbations, P. aeruginosa was isolated in a large proportion, with many not returning to baseline lung function and requiring readmission, despite antibiotic therapy. This highlights the ongoing challenge of managing chronic P. aeruginosa infections in CF.

The thesis also examines the process of isolating and purifying P. aeruginosa bacteriophages for therapeutic use. A nebulisation protocol was developed to preserve bacteriophage integrity during delivery, ensuring that bacteriophages remain viable for effective treatment. The first clinical trial of personalised bacteriophage therapy through bronchoscopic instillation followed by nebulisation in children and adolescents with CF is reported within, shows promising results, with no adverse effects and improvements in lung function. One participant achieved complete eradication of P. aeruginosa for the first time in six years, despite prior antibiotic treatments.

This research emphasises the need for innovative treatments to combat persistent P. aeruginosa infections and lays the groundwork for future clinical trials in bacteriophage therapy particularly in the battle againsts multi-drug resistant bacterial pathogens. The CHIP-CF study has expanded its criteria to include children as young as six, expanded indications to include all patients with suppurative lung disease, and plans to move to phase 2 trials, with international collaborations to further integrate bacteriophage therapy into clinical practice.