Cefiderocol nonsusceptibility among carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: data from the 2024 Antimicrobial Testing Leadership and Surveillance (ATLAS) program.

We evaluated cefiderocol activity against carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB), characterized the β-lactamase gene profiles of cefiderocol-nonsusceptible CRPA by metallo-β-lactamase (MBL) subtype, and assessed cross-resistance with comparator agents. Cefiderocol minimum inhibitory concentrations (MICs) for 890 CRPA and 1,063 CRAB isolates from the 2024 Antimicrobial Testing Leadership and Surveillance (ATLAS) program were determined by broth microdilution using iron-depleted cation-adjusted Mueller-Hinton broth. Cefiderocol nonsusceptibility was defined as MIC ≥ 8 mg/L per CLSI (intermediate + resistant). DTRPA was defined as nonsusceptible to all anti-pseudomonal β-lactams and fluoroquinolones; DTRAB was defined as nonsusceptible to carbapenems, ampicillin-sulbactam, and fluoroquinolones, reflecting species-specific susceptibility panels. CRPA isolates underwent molecular screening for blaNDM, blaVIM, blaIMP, serine carbapenemase, and ESBL genes; genotype data were not available for A. baumannii. Cefiderocol susceptibility was 93.9% for CRPA and 88.5% for CRAB, respectively (nonsusceptibility 6.1% and 11.5%, respectively; OR = 2.01, P < 0.001); nonsusceptibility among DTRPA and DTRAB was 8.1% and 11.7%, respectively. Among 54 cefiderocol-nonsusceptible CRPA, 41 (76%) harbored no detectable carbapenemase gene. Nonsusceptibility among MBL-positive CRPA was exclusively attributable to blaNDM producers (27.7%, 13/47); blaVIM-positive (n = 68) and blaIMP-positive (n = 21) isolates were uniformly susceptible. Among cefiderocol-nonsusceptible CRPA, 98.1% were co-resistant to ceftazidime-avibactam and 96.3% to ceftolozane-tazobactam.