BACKGROUND:

Pseudomonas aeruginosa (P. aeruginosa) infections are associated with worse outcomes and increased disease severity in bronchiectasis. These infections are extremely challenging to treat, with antibiotic treatments often failing to eradicate infections.

There have been multiple studies and meta-analyses suggesting antibiotics are effective in a subset of patients for treating these chronic infections and reducing the burden of disease. However, there are no licenced antibiotics for the treatment of these infections largely due to inconsistent results between replicate randomized controlled trials of antibiotics.

The ORBIT-3 and ORBIT-4 trials were replicate trials investigating the therapeutic benefit of inhaled liposomal ciprofloxacin (an inhaled antibiotic) in patients with bronchiectasis with chronic P. aeruginosa infection. ORBIT-3 showed a benefit of ciprofloxacin, while ORBIT-4 failed to show the same positive results, and it is unclear why there was a difference in response between the two trials.  

STUDY OVERVIEW:

EMBARC is currently utilising samples collected during the trial to try to:

• Explain these inconsistent trial results.
• Identify a subset of patients who are more likely to benefit from inhaled antibiotic therapy.
• Understand the heterogeneity of P. aeruginosa infections in bronchiectasis.
• Define variations in patients with chronic P. aeruginosa infection. 

To do this, EMBARC is performing multi-omic analyses, looking at the immune responses among patients, and examining differences in the bacteria present in these patients.