Pitart Cristina, Taltavull Gabriel, López-Causapé Carla, Pulgarín Andrea, De Gea Sergi, Aguilar Mireia, Mulet Xavier, Cabot Gabriel, Vila Jordi, Roca Ignasi, Espasa Mateu, Casals-Pascual Climent, Oliver Antonio
Department of Clinical Microbiology, Biomedical Diagnostic Center, Hospital Clinic, Barcelona, Spain.
Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.
JAC Antimicrob Resist. 2025 Apr 22;7(2):dlaf063. doi: 10.1093/jacamr/dlaf063. eCollection 2025 Apr.
To analyse the intrahospital and global dissemination and resistome dynamics of the concerning NDM-1 MBL-producing ST773 high-risk clone.
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.
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.
This work evidences the transborder spread and intrahospital dissemination and evolution of the emerging ST773-NDM-1 high-risk clone.
分析产NDM-1金属β-内酰胺酶的ST773高危克隆在医院内及全球范围内的传播情况和耐药组动态变化。
对2022年至2024年期间从西班牙巴塞罗那临床医院（HCB）的10名患者中分离出的17株产NDM-1菌株进行药敏试验和全基因组测序（WGS）研究。通过定量（实时）逆转录聚合酶链反应（RT-PCR）分析耐药基因的表达情况。还将从全球分离出的40个ST773基因组纳入系统发育和耐药组分析。
除1株（ST357，还产VEB-9，且在流行病学上与印度相关联）外，所有HCB产NDM-1菌株均属于ST773。首例ST773病例是一名41岁女性，2022年2月在乌克兰接受乳腺癌手术后入住肿瘤病房。这些菌株密切相关，blaNDM-1基因位于同一个117 kb的整合接合元件中。来自HCB的所有ST773-NDM-1产菌者以及40个全球分离株共享相同的获得性耐药决定因素[如blaCTX-M-15、blaTEM-1B、blaOXA-1和armA（G）]，以及一些抗生素耐药性突变（Gly238Ser、Ser83Leu、Asn170Ser和Ala114Val）。其他特定突变，如ΔISAba125缺失，仅与转移至马德里或荷兰的乌克兰患者的分离株共享。最后，HCB分离株在医院内传播过程中出现了进一步的耐药组突变，包括AmpC（ampR）和MexAB-OprM（mexR）的调节因子，与氨曲南/阿维巴坦耐药性的获得有关，因此仅对头孢地尔和黏菌素敏感。
本研究证明了新兴的ST773-NDM-1高危克隆的跨境传播、医院内传播及进化。
