(461) In Vitro Antibacterial Activity of Cefiderocol against a Multinational Collection of Pseudomonas aeruginosa isolates from Cystic Fibrosis Patients: SENTRY 2020-2021

Background: Pseudomonas aeruginosa is a major cause of lung infections in people with cystic fibrosis (CF). Cefiderocol is a parenteral siderophore cephalosporin with potent activity against Gram-negative pathogens, including P. aeruginosa. We evaluated the in vitro activity of cefiderocol and comparators against P. aeruginosa isolates collected from cystic fibrosis patients by the SENTRY Antimicrobial Surveillance Program.

Methods: A total of 137 P. aeruginosa isolates were consecutively collected from hospitalized CF patients in 32 US hospitals and 36 European Hospitals in 18 countries from 2020-2021. Susceptibility testing was performed using the broth microdilution method. Cefiderocol was tested in iron-depleted Mueller-Hinton broth. FDA, CLSI, and EUCAST (2022) breakpoints were applied. Other agents tested included meropenem, imipenem, ciprofloxacin, levofloxacin, amikacin, gentamicin, and the beta-lactam/beta-lactamase inhibitor (BL/BLI) combinations ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam, and piperacillin-tazobactam.

Results: Among 137 P. aeruginosa isolates, 80 were isolated in Europe and 57 from the United States. The majority of isolates were from non-ICU patients (119/137). Ten isolates were from patients in the ICU, and 8 isolates had no information available. Among antibiotics tested, cefiderocol was the most active antibiotic tested (99.3%, 97.1%, and 94.9% susceptibility by CLSI, EUCAST, and FDA breakpoints, respectively). Susceptibility to BL/BLI combinations ranged from 73.7% to 94.9% susceptibility, depending on the agent tested and the breakpoint utilized. 75.9% of isolates were susceptible to meropenem. Other susceptibility results are listed in Table 1. Thirty-three of the isolates were carbapenem non-susceptible (carb-NS) (defined as meropenem MIC > 2 mg/L). Against the carb-NS P. aeruginosa isolates, cefiderocol was the most active antibiotic tested (97.0%, 90.9%, and 84.8% susceptibility by CLSI, EUCAST, and FDA breakpoints, respectively). Susceptibility to the BL/BLI combinations ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and piperacillin-tazobactam by CLSI breakpoints were 84.4%, 66.7%, 75.8%, and 30.3%, respectively.

Conclusions: Cefiderocol demonstrated potent activity against P. aeruginosa isolates collected from CF patients. Results from these studies suggest that cefiderocol could provide an important treatment option for P. aeruginosa in CF patients.

Acknowledgements:

References: