• 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 Forrest, Gerd Fätkenheuer, Marcelo Gareca, Susan J Rehm, Hans Reinhardt Brodt, Alan Tice, Sara E Cosgrove, and S. aureus Endocarditis and Bacteremia Study Group.
• Duke University Medical Center, Durham, NC 27710, USA. vance.fowler@duke.edu
• N. Engl. J. Med. 2006 Aug 17; 355 (7): 653665653-65.

BackgroundAlternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed.MethodsWe 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.ResultsForty-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).ConclusionsDaptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).Copyright 2006 Massachusetts Medical Society.

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