Persistent Enterococcus faecium bacteremia with emergence of daptomycin resistance and unexpected resistance...

Persistent bacteremia due to Enterococcus spp., without an identifiable source of infection, is a well described phenomenon. Although often the preferred therapeutic agent, daptomycin resistance may develop resulting in clinical failure. In North American isolates, mutations in the LiaFSR gene complex (specifically LiaR W73C and LiaS T120A) are associated with daptomycin resistance; however these mutations also correlate with daptomycin-β-lactam synergistic activity. The case presented in this report had persistent vancomycin-resistant E. faecium bacteremia despite 26 days of daptomycin and β-lactam therapy. Initial daptomycin MICs were 2-4 µg/ml, and rose to 8 µg/ml during therapy. Whole genome sequencing revealed a mutation in the LiaFSR gene complex (S19F of LiaR) previously reported only in Australian isolates. While other mutations involving LiaFSR are associated with synergy between daptomycin and β-lactams, clinical failure of combination therapy was observed in this case. Whenever possible, additional microbiological and genomic testing should be performed on isolates of E. faecium presenting with refractory bacteremia.