September 4, 2006|
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