Bloodstream infection with NDM-1/5 Enterobacter cloacae complex in China: diverse STs, multi-virulence systems and carbapenem resistance

中国NDM-1/5型阴沟肠杆菌复合群引起的血流感染:多种序列型、多重毒力系统和碳青霉烯类耐药性

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Abstract

OBJECTIVES: To elucidate the molecular epidemiology, virulence repertoire and resistance gene characteristics of carbapenem-resistant Enterobacter cloacae complex (CRECC) in bloodstream infections (BSI), thereby providing evidence for precision therapy and infection control. METHODS: We retrospectively collected 13 non-replicate CRECC-BSI isolates from January 2019 to December 2023 at a tertiary-care hospital in Shandong Province, China. Antimicrobial susceptibility was determined by broth microdilution; Illumina NovaSeq whole-genome sequencing was performed, and genomes were assembled with ABySS and GapCloser. ResFinder, VFDB, CGE and NCBI Pathogen Detection databases were used jointly to analyze resistance genes, virulence factors, plasmid replicons, MLST an SNP-based phylogenetic tree assessed inter-strain relatedness; while filter-mating assays determined the transferability of plasmids. RESULTS: A total of 13 CRECC isolates yielded five sequence types (STs), with ST171 predominating (46.2%, 6/13); all carried bla (NDM) (bla (NDM-1) in 9 isolates, bla (NDM-5) in 4), along with AmpC, ESBLs, and aminoglycoside/quinolone resistance genes. The IncX3 plasmid replicon was most frequent (46.2%, 6/13), followed by IncHI2/HI2A (38.5%, 5/13). Each strain harbored adherence, biofilm formation, iron/manganese transport and T6SS virulence genes. Antimicrobial susceptibility testing revealed complete resistance among all isolates to cephalosporins, carbapenems and β-lactam/β-lactamase-inhibitor combinations, while amikacin, tigecycline and polymyxin B remained 100% susceptible. cgMLST revealed a polyclonal population structure. Conjugation assays demonstrated transfer of bla (NDM)-bearing plasmids to recipient Escherichia coli J53. CONCLUSIONS: Our institutional CRECC-BSI is characterized by diverse sequence types, a complex plasmid profile and a high burden of virulence genes; ST171 is the dominant clone and bla (NDM-1) the principal carbapenemase. Close surveillance of this high-risk lineage and of IncX3/IncHI2-mediated horizontal gene transfer is essential, together with strengthened infection-control and antimicrobial-stewardship measures.

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