Genomic analysis of coexisting β-lactamase plasmids in Klebsiella pneumoniae from an immunocompromised patient

• A multidrug-resistant K. pneumoniae ST147 high-risk clone was isolated from an acute myeloblastic leukemia patient. • Genomic analysis identified plasmid-mediated resistance mechanisms, virulence factors, and diverse replicon types. • Coexistence of several β-lactamase–harboring plasmids highlights complex AMR evolution within the ST147 lineage. • Findings underscore the need for strengthened genomic surveillance in high-risk, immunocompromised patient populations. Infection significantly increases morbidity and mortality in hematologic malignancies due to immunosuppression, multiple risk factors, and greater susceptibility to healthcare-associated infections. We conducted a comprehensive genomic analysis of ESBL and carbapenemase co-producing K. pneumoniae (KP-JZ177) isolate recovered from a vulnerable patient with acute myeloblastic leukemia (AML) in Jazan region, Saudi Arabia. A clinical K. pneumoniae (KP-JZ177) isolate was obtained from a wound swab of a female patient with AML in the Hematology–Oncology unit of a tertiary hospital in Jazan region. Identification and AST were performed using the MicroScan WalkAway system. Whole-genome sequencing enabled comprehensive characterization of the strain’s genetic profile, resistance determinants, virulence factors, and plasmid replicons. KP-JZ177 isolate displayed resistance to all tested antimicrobials except amikacin, gentamicin, tigecycline, and colistin. The genomic features of KP-JZ177 indicate substantial adaptability and pathogenic potential. KP-JZ177 belongs to sequence type ST147, a globally recognized high-risk clone associated with carbapenem resistance and recurrent hospital outbreaks. Its extensive drug-resistant (XDR) profile is driven by the co-occurrence of carbapenemase genes bla OXA-48 and bla NDM-1 , which together confer high-level β-lactam resistance. Serotyping classified the isolate as KL64 with an O1/O2v1 O-antigen. Genomic analysis also revealed eight plasmids, many carried β-lactamase determinants and several mobile genetic elements (MGEs). Genomic profiling of KP-JZ177 reveals high-risk K. pneumoniae clone carrying extensive resistance and virulence determinants on multiple plasmids, including bla OXA-48 and bla NDM-1 . Its plasmids similarity to geographically distant strains underscore global AMR circulation, emphasizing the need for enhanced surveillance of ST147 CRKP isolates in high-risk populations.