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Daptomycin may be an Alternative to Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus aureus

September 4, 2006

By Sahar Bedrood B.S. and Asher Kimchi M.D.

Durham, NC - Staphylococcus Aureus is a leading cause of bacteremia and endocarditis. Gentamicin plus penicillin or vancomycin is standard therapy for S. Aureus bacteremia. Vancomycin is the standard therapy for blood-stream infections attributable to methicillin-resistant S. aureus (MRSA). The standard therapy has been associated with suboptimal outcomes. Vance G. Fowler, Jr., MD, MHS, et al from Duke University Medical Center set out to establish whether daptomycin is an effective and safe treatment for S. aureus bacteremia and endocarditis. The study, published in the August 17, 2006 issue of The New England Journal of Medicine found that Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis.

The study was a open-label, randomized trial that 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 anti-staphylococcal penicillin or vancomycin.

Forty-two days after the end of the therapy, a successful outcome was noted for 53 out of 120 patients who received daptomycin as compared to 48 of 115 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). The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis and methicilin-resistant S. aureus. Daptomycin was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). As compared to daptomycin therapy, standard therapy was associated with a non-significantly higher rate of adverse events that led to treatment failure due to discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004).

The growing problem of MRSA bacteremia and endocarditis is due to clinical failure and resistance to vancomycin. This study demonstrates that daptomycin is not inferior to standard therapy for the treatment of S. aureus bacteremia and right-sided endocarditis caused by MRSA.

Co-authors: Vance G. Fowler, Jr., M.D., M.H.S., Helen W. Boucher, M.D., G. Ralph Corey, M.D., Elias Abrutyn, M.D., Adolf W. Karchmer, M.D., Mark E. Rupp, M.D., Donald P. Levine, M.D., Henry F. Chambers, M.D., Francis P. Tally, M.D., Gloria A. Vigliani, M.D., Christopher H. Cabell, M.D., M.H.S., Arthur Stanley Link, M.D., Ignace DeMeyer, M.D., Scott G. Filler, M.D., Marcus Zervos, M.D., Paul Cook, M.D., Jeffrey Parsonnet, M.D., Jack M. Bernstein, M.D., Connie Savor Price, M.D., Graeme N. Forrest, M.D., Gerd Fätkenheuer, M.D., Marcelo Gareca, M.D., Susan J. Rehm, M.D., Hans Reinhardt Brodt, M.D., Alan Tice, M.D., Sara E. Cosgrove, M.D., for the S. aureus Endocarditis and Bacteremia Study Group

 


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