This study evaluates the role of AZLI in the treatment of acute pulmonary exacerbations of CF. For consecutive exacerbations patients will receive AZLI + IV Colistin, or two IV anti-pseudomonals.

AZLI, marketed as Cayston, is an inhaled beta-lactam antibiotic. It has a license for the chronic suppression of Pseudomonas aeruginosa (PA). Current standard practice dictates the use of two IV antipseudomonal antibiotics for the treatment of acute pulmonary exacerbations. The increasing survival, and hence population, in CF means that newer antimicrobial strategies are required in order to manage antimicrobial resistance, minimise adverse systemic effects of heavy antimicrobial exposure and also make effective use of resources. Inhaled antibiotics are commonly used in the chronic suppression of PA yet their use has not been thoroughly investigated in acute pulmonary exacerbation. Inhaled antibiotics deliver their drugs directly to the target-site with minimal systemic absorbance, making them an attractive candidate for treatment of acute exacerbations.

Recently, it has become apparent that the bacterial community is much more complex than initially thought. The microbiome, a term used to describe the polymicrobial community in the lungs, has become apparent due to the use of modern culture-independent methods to detect bacteria. The microbiome changes in composition and structure around the time of exacerbations and in response to treatment, although these changes have not been prospectively characterised.

We have designed an open-label randomised, controlled cross-over trial to investigate the clinical effectiveness of of AZLI in the treatment of acute pulmonary exacerbation, whilst simultaneously comparing the effect inhaled and intravenous antibiotics have on the microbiome.

Inclusion Criteria:

1. Confirmed diagnosis of CF
2. Patients aged 18 - 65 years of age who can give informed consent
3. FEV1 >25% or <75% predicted (in keeping with Cayston® license)
4. Admitted to the Liverpool Heart & Chest Hospital with an exacerbation of CF pulmonary disease
5. Presence of PA in lower respiratory tract cultures in the 6 months prior

Exclusion Criteria:

1. Documented allergy to beta-lactam antibiotics or IV Colistin
2. Growth of Burkholderia Cepacia Complex (BCC) within 2 years
3. Pregnancy
4. Previous organ transplant
5. Receiving other clinical trial medication
6. Already prescribed regular Cayston®