Development of Linezolid and Daptomycin resistance in Vancomycin Resistant Enterococcus Faecium During Antibiotic Treatment
The increasing incidence of vancomycin-resistant enterococci (VRE) over the past decade has reduced treatment options largely to linezolid and daptomycin. However, the emergence of re-sistance to both agents further complicates the management of VRE infections. While the mecha-nisms of linezolid resistance are relatively well understood, those underlying daptomycin resistance remain less clearly defined. In this study, we analyzed genomic changes associated with the devel-opment of linezolid and daptomycin resistance in initially susceptible isolates following treatment. Phenotypic susceptibility testing and whole-genome sequencing (WGS) were performed on eight isolates obtained from the same patient. We identified two distinct E. faecium clones with different mechanisms of linezolid resistance. One clone also developed daptomycin resistance during thera-py. Linezolid resistance was associated with a G2676T mutation in the 23S rRNA gene (clone 1) and a mutation in the poxtA gene (clone 2). Daptomycin resistance appeared to result from either a G173R substitution in a gene annotated as an ABC transporter ATP-binding protein (LolD) or a nonsense mutation (Q58*) in phosphoketolase, with both alterations potentially acting synergistical-ly. Together with these findings, the study demonstrate that a single patient may harbor multiple E. faecium clones simultaneously, highlighting the risk of treatment failure if all clones are not accu-rately identified.