Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus aureus
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
Background Alternative therapies for Staphylococcus aureus bacteremiaand endocarditis are needed.
Methods We randomly assigned 124 patients with S. aureus bacteremiawith or without endocarditis to receive 6 mg of daptomycin intravenouslyper kilogram of body weight daily and 122 to receive initiallow-dose gentamicin plus either an antistaphylococcal penicillinor vancomycin. The primary efficacy end point was treatmentsuccess 42 days after the end of therapy.
Results Forty-two days after the end of therapy in the modifiedintention-to-treat analysis, a successful outcome was documentedfor 53 of 120 patients who received daptomycin as compared with48 of 115 patients who received standard therapy (44.2 percentvs. 41.7 percent; absolute difference, 2.4 percent; 95 percentconfidence interval, 10.2 to 15.1 percent). Our resultsmet prespecified criteria for the noninferiority of daptomycin.The success rates were similar in subgroups of patients withcomplicated bacteremia, right-sided endocarditis, and methicillin-resistantS. aureus. Daptomycin therapy was associated with a higher rateof microbiologic failure than was standard therapy (19 vs. 11patients, P=0.17). In 6 of the 19 patients with microbiologicfailure in the daptomycin group, isolates with reduced susceptibilityto daptomycin emerged; similarly, a reduced susceptibility tovancomycin was noted in isolates from patients treated withvancomycin. As compared with daptomycin therapy, standard therapywas associated with a nonsignificantly higher rate of adverseevents that led to treatment failure due to the discontinuationof therapy (17 vs. 8, P=0.06). Clinically significant renaldysfunction occurred in 11.0 percent of patients who receiveddaptomycin and in 26.3 percent of patients who received standardtherapy (P=0.004).
Conclusions Daptomycin (6 mg per kilogram daily) is not inferiorto standard therapy for S. aureus bacteremia and right-sidedendocarditis. (ClinicalTrials.gov number, NCT00093067
[ClinicalTrials.gov]
.)
Source Information
From Duke University Medical Center, Durham, N.C. (V.G.F., G.R.C., C.H.C.); Tufts New England Medical Center (H.W.B.) and Beth Israel Deaconess Medical Center (A.W.K.) both in Boston; Drexel University College of Medicine, Philadelphia (E.A.); University of Nebraska Medical Center, Omaha (M.E.R.); Wayne State University School of Medicine, Detroit (D.P.L.); San Francisco General Hospital, San Francisco (H.F.C.); Cubist Pharmaceuticals, Lexington, Mass. (F.P.T., G.A.V.); Forsyth Medical Center, Winston-Salem, N.C. (A.S.L.); Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium (I.D.); HarborUCLA Medical Center, Torrance, Calif. (S.G.F.); William Beaumont Hospital, Royal Oak, Mich. (M.Z.); East Carolina University, Greenville, N.C. (P.C.); DartmouthHitchcock Medical Center, Lebanon, N.H. (J.P.); Veterans Affairs Medical Center, Dayton, Ohio (J.M.B.); Denver Health Medical, Denver (C.S.P.); University of Maryland School of Medicine (G.N.F.), Johns Hopkins University School of Medicine (S.E.C.) both in Baltimore; Klinikum, University of Cologne, Cologne, Germany (G.F.); Lehigh Valley Hospital Trauma and Critical Care Research, Allentown, Pa. (M.G.); Cleveland Clinic Foundation, Cleveland (S.J.R.); Johann Wolfgang Goethe Universität, Frankfurt, Germany (H.R.B.); and University of Hawaii, and Queens Medical Center both in Honolulu (A.T.).
Address reprint requests to Dr. Fowler at Box 3281, Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, or at vance.fowler{at}duke.edu.
Therapy for Methicillin-Resistant Staphylococcus aureus
Siegman-Igra Y., Torres-Tortosa M., Caballero-Granado F. J., Canueto J., Jetton L., Cosgrove S. E., Fowler V. G. Jr., Boucher H. W., Moran G. J., Talan D. A.
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N Engl J Med 2006;
355:2153-2155, Nov 16, 2006.
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