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

Background Pseudomonas aeruginosa is a key pathogen in cystic fibrosis (CF), driving pulmonary decline and exhibiting resistance through virulence factors and adaptive mutations. Cefiderocol (FDC) is a novel siderophore cephalosporin with activity against Gram-negative bacteria. We aimed to assess the in vitro efficacy of FDC against P. aeruginosa isolates in a CF population.     Methods The study was conducted in a tertiary hospital with a specialist adult CF service. All first isolates of significant respiratory pathogens among this cohort are cryopreserved at -80°C. Antimicrobial susceptibility testing to FDC was performed as per European Committee on Antimicrobial Susceptibility Testing (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 included. Resistance phenotypes comprised 19% (n=16) multidrug-resistant (MDR), 16% (n=14) extensively drug-resistant (XDR) and 24% (n=20) pandrug-resistant (PDR); with 24% (n=20) exhibiting the mucoid phenotype. Overall, 85% of isolates were susceptible to FDC, with a mean inhibition zone of 25.2 mm. Antimicrobial activity was retained in 81% of MDR, 86% of XDR, 60% of PDR and 90% of mucoid isolates. 74% of meropenem-non-susceptible isolates remained susceptible to FDC, compared with lower susceptibility to ceftolozane–tazobactam (42%), tobramycin (36%) and ciprofloxacin (22%).   Conclusion FDC exhibited excellent in vitro activity against P. aeruginosa from adults with CF, including highly resistant and mucoid phenotypes. These findings highlight its potential as a salvage option in this high-risk population and provide the first Irish surveillance data to inform antimicrobial stewardship and future clinical use.