In vitro activity of cefiderocol against Pseudomonas aeruginosa isolated from adult patients with cystic fibrosis

Background Pseudomonas aeruginosa is an opportunistic pathogen that commonly infects the cystic fibrosis (CF) lung, promoting a rapid decline in pulmonary function. It exhibits significant resistance to innate immune effectors and antimicrobials by expressing specific virulence factors and by acquiring adaptive mutations during chronic infection, often proving challenging when devising effective treatment regimens. Cefiderocol (FDC) is a novel siderophore cephalosporin with activity against Gram-negative pathogens. We aimed to assess the in vitro efficacy of cefiderocol against P. aeruginosa isolates in a CF population. Methods The study was conducted in a tertiary hospital with a specialist adult CF service caring for approximately 300 patients. All first isolates of significant respiratory pathogens among this cohort are cryopreserved at -80°C. Antimicrobial susceptibility testing to FDC was performed as per EUCAST Disk-Diffusion (Version 10) for all stored isolates of P. aeruginosa from 2017-2022 inclusive.    Results Eighty-five isolates from seventy-one patients were examined during the study period. The average age of patients was 30 years, with the average age at which P. aeruginosa was first isolated being 24 years (IQR 18-28) and the average age of isolation of a mucoid phenotype being 32 years (IQR 25-38). Forty-one percent (n=35) of isolates were classified as non-multidrug-resistant, 19% (n=16) multidrug-resistant, 16% (n=14) extensively drug-resistant and 24% (n=20) pandrug-resistant; with 24% (n=20) exhibiting the mucoid phenotype. With a zone of ≥22 mm indicating susceptibility to FDC, only 13 isolates (15%) were deemed non-susceptible, with an overall average disk-diffusion zone of 25.2 mm.   Conclusion Cefiderocol exhibited excellent in vitro anti-pseudomonal activity against isolates obtained from an adult CF population.