Genomic epidemiology and clinical characteristics of linezolid-resistant Enterococcus faecalis in Taiwan, 2014-2020

Linezolid-resistant Enterococcus faecalis (LREfs) is emerging globally. We investigated the temporal trends and genomic architecture of LREfs through the nationwide surveillance and evaluated the predictors for LREfs bloodstream infections (BSI) in an independent clinical cohort.

Clinical isolates were collected via the Taiwan Surveillance of Antimicrobial Resistance programs (2014-2020). De novo assemblies were completed using hybrid (MinION/Illumina) or PacBio HiFi sequencing. A matched case-control BSI cohort assessed the association between prior antibiotic exposure and resistance acquisition.

LREfs prevalence rose significantly from 2014-2016 to 2018-2020 (1.5% vs 8.9%, P < 0.001). Among 54 LREfs isolates, clonal complex CC480 (37.0%) and CC16 (29.6%) predominated. The optrA gene was present in 96.3% of isolates, with 86.8% of copies chromosomally integrated within the Tn6674 transposon among two prevalent CCs and other sequence types. Conversely, plasmid-mediated resistance driven by IS1216E or other insertion sequences was sporadic. Multi-gene co-carriage (optrA, poxtA, and cfr) was rare and exclusively plasmid-borne. In the clinical cohort, prior linezolid exposure was not associated with LREfs acquisition.

E. faecalis has emerged as a primary linezolid resistance reservoir. The chromosomal fixation of Tn6674-encoded optrA facilitates the widespread distribution of these major lineages, allowing resistance to persist even in absence of recent direct linezolid exposure.