Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus

Vance G. Fowler, Helen W. Boucher, G. Ralph Corey, Elias Abrutyn, Adolf W. Karchmer, Mark E. Rupp, Donald P. Levine, Henry F. Chambers, Francis P. Tally, Gloria A. Vigliani, Christopher H. Cabell, Arthur Stanley Link, Ignace DeMeyer, Scott G. Filler, Marcus Zervos, Paul Cook, Jeffrey Parsonnet, Jack M. Bernstein, Connie Savor Price, Graeme N. ForrestGerd Fätkenheuer, Marcelo Gareca, Susan J. Rehm, Hans Reinhardt Brodt, Alan Tice, Sara E. Cosgrove

Research output: Contribution to journalArticle

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Abstract

Background: Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. Methods: We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. Results: Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). Conclusions: Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis.

Original languageEnglish (US)
Pages (from-to)653-665
Number of pages13
JournalNew England Journal of Medicine
Volume355
Issue number7
DOIs
StatePublished - Aug 17 2006

ASJC Scopus subject areas

  • Medicine(all)

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    Fowler, V. G., Boucher, H. W., Corey, G. R., Abrutyn, E., Karchmer, A. W., Rupp, M. E., Levine, D. P., Chambers, H. F., Tally, F. P., Vigliani, G. A., Cabell, C. H., Link, A. S., DeMeyer, I., Filler, S. G., Zervos, M., Cook, P., Parsonnet, J., Bernstein, J. M., Price, C. S., ... Cosgrove, S. E. (2006). Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. New England Journal of Medicine, 355(7), 653-665. https://doi.org/10.1056/NEJMoa053783