Emergence of a daptomycin-non-susceptible Enterococcus faecium strain that encodes mutations in DNA repair genes after high-dose daptomycin therapy.

BMC Res Notes, 2016/4/01;9:197.

Matono T[1], Hayakawa K[2], Hirai R[3], Tanimura A[3], Yamamoto K[1], Fujiya Y[1], Mawatari M[1], Kutsuna S[1], Takeshita N[1], Mezaki K[4], Ohmagari N[1], Miyoshi-Akiyama T[5]

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PMID: 27036708DOI: 10.1186/s13104-016-2003-9

Abstract
background: An increasing number of reports have documented the emergence of daptomycin-nonsusceptible Enterococcus in patients during daptomycin therapy. Even though several mechanisms for daptomycin-nonsusceptibility have been suggested, the potential genetic mutations which might contribute to the daptomycin-nonsusceptibility are not fully understood.
case presentation: We isolated a vancomycin-susceptible, daptomycin nonsusceptible Enterococcus faecium strain from a patient with acute lymphocytic leukemia who received high-dose daptomycin therapy for E. faecium endocarditis. Whole-genome sequencing analysis revealed mutations within genes encoding DNA repair proteins MutL and RecJ of the daptomycin-nonsusceptible Enterococcus strain which might have facilitated its emergence.
conclusions: We identified the mutations of DNA mismatch repair genes in a clinical isolate of daptomycin nonsusceptible E. faecium which emerged in spite of high-dose daptomycin therapy. The finding implicates the possible association of DNA repair mechanism and daptomycin resistance. Careful monitoring is necessary to avoid the emergence of daptomycin non-susceptible isolates of E. faecium and particularly in cases of long-term daptomycin use or in immunocompromised patients.

Keywords: Daptomycin; E. faecium; Whole-genome sequence

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