Analysis of intrahospital and global dissemination and resistome dynamics of NDM-1-producing ST773 high-risk clone.

Objectives: To analyse the intrahospital and global dissemination and resistome dynamics of the concerning NDM-1 MBL-producing ST773 high-risk clone.

Methods: A total of 17 NDM-1-producing isolates recovered in 2022-24 from 10 patients at Hospital Clinic of Barcelona (HCB), Spain, were studied through susceptibility testing and WGS. Expression of resistance genes was analysed through quantitative (real-time) RT-PCR. Forty ST773 genomes from isolates recovered worldwide were also incorporated in the phylogenetic and resistome analysis.

Results: All HCB NDM-1-producing isolates were assigned to ST773 except one (ST357 additionally producing VEB-9 and linked epidemiologically to India). The index ST773 case was a 41-year-old woman admitted to the oncology ward in February 2022 after breast cancer surgery in Ukraine. These isolates were closely related and the gene was located in the same 117 kb integrative conjugative element. All ST773-NDM-1 producers from HCB and the 40 worldwide isolates shared the same acquired resistance determinants [like, , and (G)], as well as some of the antibiotic resistance mutations (, , and ). Other specific mutations such as an deletion were shared only with isolates from Ukrainian patients transferred to Madrid or the Netherlands. Lastly, HCB isolates evolved further resistome mutations during intrahospital dissemination, including regulators of AmpC () and MexAB-OprM (), linked to the acquisition of aztreonam/avibactam resistance, and thus remaining only susceptible to cefiderocol and colistin.

Conclusions: This work evidences the transborder spread and intrahospital dissemination and evolution of the emerging ST773-NDM-1 high-risk clone.