Daptomycin is a lipopeptide antimicrobial used for the treatment of aerobic gram-positive skin and soft tissue infections. We describe a patient with acute myeloid leukemia whose febrile neutropenia was treated with daptomycin and who later developed daptomycin-resistant Enterococcus faecium infection. Defervescence and negative blood cultures ensued after treatment with linezolid. Guidelines for testing daptomycin susceptibilities of enterococci include breakpoints only for vancomycin-susceptible Enterococcus faecalis, making interpretation of minimum inhibitory concentrations for common clinical infections difficult. No enterococcal cross-resistance has been reported among daptomycin, linezolid, or quinupristin-dalfopristin, and these agents may be viable alternatives.
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