Abstract
INTRODUCTION: Acinetobacter baumannii is a leading cause of healthcare-associated infections in immunocompromised patients and frequently exhibits multidrug resistance. Cefiderocol, a siderophore cephalosporin, is among the few remaining therapeutic options for infections caused by carbapenem-resistant A. baumannii (CRAB); however, its activity may differ by clonal lineage and can be further compromised in the biofilm state. This study investigates genomic features and cefiderocol efficacy against planktonic and biofilm-associated forms of oncology-derived A. baumannii isolates. METHODS: Twenty-five non-duplicate, consecutive clinical isolates of A. baumannii from oncology patients underwent whole-genome sequencing and multilocus sequence typing. Cefiderocol activity was quantified in planktonic and biofilm-associated states using minimum bactericidal concentration (MBC) and minimum biofilm eradication concentration (MBEC) assays. RESULTS: Ten sequence types were identified, with the high-risk sequence type 2 (ST2) clone accounting for 56% (14/25) of isolates. ST2 strains showed significantly higher resistance to aminoglycosides, carbapenems, and fluoroquinolones than non-ST2 (NST) strains. The carbapenemase gene bla (OXA-23) was detected exclusively in ST2. Colistin and cefiderocol were the most active agents overall. ST2 strains showed higher cefiderocol MBC values than NST strains. However, avibactam significantly reduced cefiderocol MBC in ST2, consistent with class D β-lactamases activity. ST2 and NST isolates exhibited comparable distributions of iron acquisition genes and similar CAS-detected siderophore activity under the assay conditions tested. Cefiderocol activity was significantly reduced in biofilms relative to planktonic cells (median MBEC 2 µg/ml versus median MBC 0.5 µg/ml). NST exhibited higher MBEC/MBC ratios than ST2 isolates, indicating greater biofilm-associated tolerance to cefiderocol. DISCUSSION: Collectively, these data associate the predominance of oncology-derived ST2 with bla (OXA-23) carriage and higher cefiderocol bactericidal thresholds and show that cefiderocol activity is consistently reduced in the biofilm state. Future studies integrating functional measures of iron acquisition and β-lactamase activity will be needed to define the determinants of cefiderocol efficacy across lineages and growth states.