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Current Microbiology, vol.83, no.6, 2026 (SCI-Expanded, Scopus)
Pseudomonas aeruginosa remains one of the most formidable Gram-negative pathogens due to its extensive β-lactamase repertoire and rapidly evolving multidrug resistance. Cefiderocol, a novel siderophore cephalosporin, has emerged as a promising option against carbapenem-resistant isolates; however, its activity may be compromised in the presence of class A β-lactamases. Avibactam, a potent inhibitor of class A, class C, and selected class D β-lactamases, offers a rational strategy to restore cefiderocol efficacy. In this study, the in vitro activity of cefiderocol alone and in combination with avibactam was evaluated against 38 non-duplicate clinical carbapenem-resistant P. aeruginosa isolates collected at Hacettepe University. Antimicrobial susceptibility was assessed by disc diffusion, gradient test, and broth microdilution, while β-lactamase genes were identified by PCR and sequencing. The cefiderocol–avibactam combination was tested using a fixed avibactam concentration of 4 mg/L. Cefiderocol resistance was detected in 84.2% of isolates, with blaVEB, blaPER, and blaVIM being the most prevalent resistance determinants. Notably, the addition of avibactam produced a pronounced ≥ 8.5-fold mean reduction in cefiderocol minimum inhibitory concentrations among class A β-lactamase producers and restored susceptibility in 21 of 36 resistant isolates, whereas metallo-β-lactamase–producing strains showed minimal response. Overall, the cefiderocol–avibactam combination demonstrated significantly enhanced in vitro activity compared with cefiderocol alone (p < 0.00001), underscoring its potential clinical value as a rescue therapeutic option for infections caused by extended-spectrum β-lactamase–producing, carbapenem-resistant P. aeruginosa.