title: Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.
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. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. vance.fowler@duke.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.forename: Helen W
authors.initials: HW
authors.lastname: Boucher
authors.forename: G Ralph
authors.initials: GR
authors.lastname: Corey
authors.forename: Elias
authors.initials: E
authors.lastname: Abrutyn
authors.forename: Adolf W
authors.initials: AW
authors.lastname: Karchmer
authors.forename: Mark E
authors.initials: ME
authors.lastname: Rupp
authors.forename: Donald P
authors.initials: DP
authors.lastname: Levine
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
authors.forename: Francis P
authors.initials: FP
authors.lastname: Tally
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Vigliani
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Cabell
authors.forename: Arthur Stanley
authors.initials: AS
authors.lastname: Link
authors.forename: Ignace
authors.initials: I
authors.lastname: DeMeyer
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.forename: Marcus
authors.initials: M
authors.lastname: Zervos
authors.forename: Paul
authors.initials: P
authors.lastname: Cook
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Parsonnet
authors.forename: Jack M
authors.initials: JM
authors.lastname: Bernstein
authors.forename: Connie Savor
authors.initials: CS
authors.lastname: Price
authors.forename: Graeme N
authors.initials: GN
authors.lastname: Forrest
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Marcelo
authors.initials: M
authors.lastname: Gareca
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Rehm
authors.forename: Hans Reinhardt
authors.initials: HR
authors.lastname: Brodt
authors.forename: Alan
authors.initials: A
authors.lastname: Tice
authors.forename: Sara E
authors.initials: SE
authors.lastname: Cosgrove
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D017576:Daptomycin / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use; D006801:Humans; D008297:Male; D016106:Methicillin Resistance; D008875:Middle Aged; D010406:Penicillins / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010406:Penicillins; D014640:Vancomycin; D017576:Daptomycin