Ciprofloxacin resistance in <i>Pseudomonas aeruginosa</i> from people with bronchiectasis

Ciprofloxacin, a key antibiotic for P. aeruginosa eradication and managing pulmonary exacerbations, has also been studied as a long-term treatment via liposomal inhalation in chronic infections (ORBIT-3/ORBIT-4). This thesis investigates ciprofloxacin resistance in clinical P. aeruginosa isolates from bronchiectasis patients enrolled in the iBEST-1 trial.

Phenotypic, DNA- and RNA-based analyses, combined with experimental evolution studies under planktonic and biofilm growth conditions, had been carried out. Resistance correlated with fluoroquinolone prescriptions and was driven by mutations in quinolone resistance-determining regions (QRDR) of gyrA and parC, along with mexEF-OprN efflux pump overexpression. These mutations also coincided with impaired motility (swimming and swarming), reduced pyocyanin production, and slower growth, characteristic of chronic respiratory adaptations.