Molecular epidemiology and genetic determinants of β-lactam resistance in Pseudomonas aeruginosa isolates from patients with cystic fibrosis in Stockholm, Sweden

OBJECTIVES: Pseudomonas aeruginosa (PA), an opportunistic Gram-negative pathogen, is a leading cause of severe pulmonary infections in individuals with cystic fibrosis (CF). A significant proportion of patients become chronically infected, with negative consequences on respiratory function. Repeated or long-time suppressive antimicrobial treatment is often necessary, promoting development of antimicrobial resistance. Certain clones are particularly successful because of enhanced transmissibility and resistance development. We aimed to characterize the molecular epidemiology and genomic basis of β-lactam resistance in PA isolates from patients with CF in Sweden. METHODS: We performed whole genome sequencing and genomic characterization of 26 PA isolates collected from patients with CF at Karolinska University Hospital, Sweden. RESULTS: repressors were prevalent. Notably, cefiderocol-resistant CF isolates had putative loss-of-function mutations in some iron metabolism-associated genes not found in cefiderocol-susceptible isolates, suggesting their role in resistance. CONCLUSIONS: The results highlight the burden of antimicrobial resistance in CF-associated PA, distinct genetic determinants of resistance and the spread of epidemic clone AUST-03 in Swedish patients with CF. These insights can inform antimicrobial therapy and infection control measures.