Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.
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].).
Fowler
Vance G
VG
Duke University Medical Center, Durham, NC 27710, USA. vance.fowler@duke.edu
Boucher
Helen W
HW
Corey
G Ralph
GR
Abrutyn
Elias
E
Karchmer
Adolf W
AW
Rupp
Mark E
ME
Levine
Donald P
DP
Chambers
Henry F
HF
Tally
Francis P
FP
Vigliani
Gloria A
GA
Cabell
Christopher H
CH
Link
Arthur Stanley
AS
DeMeyer
Ignace
I
Filler
Scott G
SG
Zervos
Marcus
M
Cook
Paul
P
Parsonnet
Jeffrey
J
Bernstein
Jack M
JM
Price
Connie Savor
CS
Forrest
Graeme N
GN
Fätkenheuer
Gerd
G
Gareca
Marcelo
M
Rehm
Susan J
SJ
Brodt
Hans Reinhardt
HR
Tice
Alan
A
Cosgrove
Sara E
SE
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
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010406:Penicillins; D014640:Vancomycin; D017576:Daptomycin