Abstract
Abstract Background Antimicrobial resistance has evolved into a complex global issue involving many clinically relevant organisms. Among these pathogens, carbapenem-resistant organisms (CROs) are of particular concern due to their limited treatment options and high mortality rates. In collaboration with Solu, whole-genome sequencing (WGS) was performed on clinical isolates recovered from our patient population to gain a better insight into resistance mechanisms present and their direct effect on clinical outcomes. Methods For genomic characterization (WGS), a total of 109 carbapenem resistant isolates across three clinically relevant bacterial groups (Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii complex) were sequenced. Solu utilized a hybrid assembly approach utilizing both long reads generated with Oxford Nanopore Technologies (ONT) complemented by Illumina short reads for the reconstruction of bacterial genomes. Results Multilocus sequence typing (MLST) revealed genetic diversity among all three groups of bacterial isolates. Among members of the family Enterobacterales, there were eight distinct sequence types: ST-131, ST-1431, ST-167, ST-2155, ST-361, ST-410, ST-685 and ST-405. A. baumannii complex strains mostly comprised of ST-2 and ST-1022. The presence of numerous sequence types was observed with the P. aeruginosa isolates, highlighting the biocomplexity within our patient population. Furthermore, genomic analysis of these isolates disclosed a broad range of antimicrobial resistance genes that span across several classes of antibiotics. Isolates across all genera harbored plasmid-mediated carbapenemase genes bla-NDM-5, bla-NDM1, bla-OXA-48 and bla-OXA23. Interestingly, cefiderocol resistance was primarily associated with the Escherichia coli ST-405 strain containing AMR gene bla-NDM5. Patients associated with a carbapenemase-producing strain were observed to have higher mortality rates (12.8%) and longer length of hospital stay (25.6%). Conclusion By having a comprehensive insight into the genomic composition of isolates that make up our patient population, we can provide a more targeted medical treatment approach and investigate and better prevent transmission events. Disclosures All Authors: No reported disclosures
Published Version
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