Genomic Insights of two Acinetobacter non-baumannii strains with uncommon mechanisms of resistance leading to cefiderocol resistance

The emergence of antimicrobial resistance in Acinetobacter species poses a significant clinical challenge, particularly in non-baumannii species, which are often overlooked in healthcare settings. In this study, we characterized two Acinetobacter clinical isolates, AMA204 and AMA207—identified as A. junii and A. haemolyticus, respectively—which exhibit uncommon resistance mechanisms that enable survival in the presence of cefiderocol, regardless of their initial minimum inhibitory concentration values. Whole-genome sequencing and comparative genomic analyses were performed to investigate the genetic determinants associated with their resistance profiles. Antimicrobial susceptibility testing confirmed multidrug resistance, with both isolates harboring key β-lactamase genes, including blaOXA-58, and blaNDM-1 in AMA204, and blaOXA-58 and blaPER-2 in AMA207. Phylogenomic analyses revealed genetic relatedness to geographically diverse isolates, suggesting possible evolutionary trends and transmission dynamics. Additionally, iron uptake systems were analyzed, highlighting potential mechanisms contributing to cefiderocol resistance together with the presence of listed β-lactamase. This study underscores the clinical relevance of non-baumannii Acinetobacter species in antimicrobial resistance and emphasizes the need for continued surveillance and novel therapeutic strategies to combat these emerging threats.