Abstract
Pseudomonas aeruginosa (P. aeruginosa) is a common cause of airway infections in people with cystic fibrosis (pwCF). Nebulised levofloxacin is the latest inhaled antibiotic available to manage chronic P. aeruginosa infections in pwCF. Little data is currently available on how this therapy is practically used in CF clinics or how P. aeruginosa isolates respond to levofloxacin exposure and the impact of antibiotic rotation during the administration of long-term inhaled antibiotic regimens. This thesis aimed to (i) determine how inhaled antibiotics are currently used in CF centres across Europe and the place of nebulised levofloxacin in the treatment of chronic P. aeruginosa infections, (ii) the impact of in vitro levofloxacin exposure and subsequent antibiotic rotation on levofloxacin resistance development in clinical P. aeruginosa isolates from pwCF, and (iii) the underlying genomic mechanisms contributing to levofloxacin resistance. The results of this thesis aim to provide an insight into the current use of nebulised levofloxacin in the clinic as well as a better understanding of the development of in vitro levofloxacin resistance in P. aeruginosa and the genetic mechanisms contributing to this. These results could inform the design of future inhaled antibiotic regimens to reduce the risk of resistance development in P. aeruginosa and ensure continued efficacy for current and future pwCF.Thesis is embargoed until 31st December 2027.
| Date of Award | Dec 2024 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Sponsors | Chiesi Ltd |
| Supervisor | Damian Downey (Supervisor) & Laura Sherrard (Supervisor) |
Keywords
- Levofloxacin
- Pseudomonas aeruginosa
- cystic fibrosis
- antimicrobial resistance
- inhaled antibiotics
- respiratory pathogens
- in vitro evolution
- whole genome sequencing
- antimicrobial prescribing