Clonal spread of linezolid-, tigecycline-, and vancomycin-resistant Enterococcus faecium isolates co-harbouring transferable optrA, vanA and tet(M) variant.

OBJECTIVES: This study investigated the clonal dissemination and molecular basis of linezolid-, tigecycline- and vancomycin-resistant E. faecium (LTVRE) isolates in a surgical intensive care unit (SICU) of a Chinese hospital.

METHODS: Three LTVRE isolates collected from patients in the SICU were subjected to antimicrobial susceptibility testing and whole-genome sequencing analysis. S1 nuclease pulsed-field gel electrophoresis was performed to verify the topology of plasmids. Conjugation experiments were conducted to evaluate the transferability of resistance determinants.

RESULTS: WGS analysis demonstrated that the three LTVRE belonged to the same clone (Sequence Type 78). The optrA and vanA genes were co-located on a transferable large linear plasmid (327.5 kb in size) and contributed resistance to linezolid and vancomycin. A tet(M) variant carrying a phenylalanine-to-isoleucine substitution at Position 473 (F473I) was identified within a Tn916-like transposon. Although chromosomally encoded, this element retains the capacity for horizontal transfer to E. faecium BM4105RF and conferred tigecycline resistance.

CONCLUSIONS: Our findings reveal a resistance dissemination strategy in which plasmid-borne and chromosomal mobile genetic elements independently or cooperatively drive the spread of resistance to last-line antibiotics and highlight the urgent need for enhanced surveillance of multidrug-resistant E. faecium, such as LTVRE.