Why carry out this study?

Enterococcus faecium is one of the two clinically important enterococcal species, causing an increasing number of hospital-acquired infections (HAIs). Although isolates with both vanA and vanB vancomycin-resistance determinants as well as isolates resistant to “last resort” drugs linezolid and tigecycline have been reported, they remain rare or even very rare, and this combination of resistance phenotypes is very unusual.

The study was performed on a clinical E. faecium isolate demonstrating a concomitant resistance to vancomycin, linezolid and tigecycline and reduced susceptibility to daptomycin. We aimed at answering the question of what the character and possible origins of resistance determinants to antimicrobials in this isolate were and what the possibility of their further horizontal dissemination.

What was learned from the study?

We established the complete genome of the isolate, and on this basis we identified it as a representative of sequence type 18, typical for hospital meroclone of E. faecium. The vanA determinant was located in Tn1546 in a 39.5-kb transferable plasmid while vanB resided in Tn1549 on a chromosome. Linezolid and tigecycline resistance was due to the acquisition of a 42.4-kb transferable plasmid, carrying poxtA and tet(M)/tet(L) genes.

Although E. faecium is well known for accumulation of various antimicrobial resistance determinants, the studied isolate was a particularly striking example of this phenomenon. Genomic analyses revealed different mechanisms beyond acquisition of a plethora of antimicrobial resistance determinants, in several cases facilitated by mobile genetic elements.

Appearance of a strain with extremely limited treatment options and ability to further disseminate genes conferring resistance to glycopeptides, linezolid and tigecycline are particularly worrisome.