Emergence of unusual vanA/vanB2 genotype in a highly mutated vanB2-vancomycin-resistant hospital-associated E. faecium background in Vietnam

Abstract Enterococcus faecium has become a globally disseminated nosocomial pathogen mainly because of acquisition and diffusion of virulence factors and multidrug resistance determinants, including glycopeptides, which are some of the last resort antimicrobials used to treat more serious infections common in high-risk patients. In this study we investigated and characterized hospital-associated (HA) E. faecium isolates collected at Hue Central Hospital, Vietnam. Our results highlighted the spread among hospital wards of a surprisingly heterogeneous multidrug-resistant E. faecium population comprising five different CC17-related sequence types (STs), of which 46% VREf carry the vanB gene. Whole genome sequencing of selected E. faecium isolates showed that VREf from different STs carried the same chromosomal integrated Tn1549-like transposon, with a highly mutated vanB2-operon, showing an increased level of vancomycin resistance (VanB phenotype) and able, in one isolate, to confer resistance to teicoplanin (VanA incongruent phenotype). Two unusual vanA/vanB 2 -type strains were detected within the vanB 2 -type ST17 population, harbouring a Tn 1546- vanA-like transposon in pJEG40-like plasmids. Wg-SNPs-based analysis showed the genetic relatedness of VSEf/VREf of the same STs and indicated lateral exchange of the Tn 1549 -like element among isolates followed by clonal expansion. Microevolution among ST17 isolates, including the vanA/vanB 2 -type strains, and inter-wards VREf transmission, were highlighted. The use of teicoplanin is strongly discouraged in the study hospital because of the spreading of Tn 1549 – vanB 2 associated to teicoplanin resistance. A rational use of glycopeptides and effective surveillance measures are required to reduce nosocomial VSEF/VREf spread and to avoid the rise of unusual and misleading VREf genotypes.