Daptomycin for Bacteremia and Endocarditis Caused by Staphylococcus Aureus - Daptomycin for Bacteremia and Endocarditis


The goal of the trial was to evaluate treatment with daptomycin compared with standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.

Study Design

Study Design:

Patients Enrolled: 124
Mean Follow Up: 42 days
Female: 40

Patient Populations:

≥1 blood culture positive for S. aureus within 2 days of randomization


Creatinine clearance <30 ml/min, known osteomyelitis, polymicrobial bacteremia, or pneumonia

Primary Endpoints:

Treatment success 42 days after the end of therapy, evaluated for noninferiority; failure was defined as clinical failure, microbiologic failure, death, failure to obtain blood culture, receipt of potentially effective nonstudy antibiotics, or adverse event leading to premature discontinuation of study medication

Drug/Procedures Used:

Patients with S. aureus bacteremia with or without endocarditis were randomized to daptomycin (6 mg/kg intravenously) (n = 120) or standard therapy (n = 115) with either vancomycin (1 g every 12 hours with dose adjustment) or an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) (2 g every 4 hours).

Principal Findings:

Median duration of therapy was 14 days in the daptomycin group and 15 days in the standard therapy group. Methicillin-resistant S. aureus (MRSA) was isolated in 38% of patients. Injection drug use was reported in 21% of patients.

The primary endpoint of treatment success 42 days after end of therapy in the modified intent-to-treat population occurred in 44.2% of the daptomycin group and 41.7% of the standard therapy group, a 2.4% absolute difference (95% confidence interval [CI] -10.2% to 15.1%) meeting the prespecified criteria for noninferiority. In the subgroup of patients with MRSA, treatment success trended in favor of daptomycin (44.4% for daptomycin vs. 31.8% for standard therapy, p = 0.28), but did not differ in the subgroup of patients with methicillin-susceptible S. aureus (MSSA) infection (44.6% vs. 48.6%, p = 0.74).

Reason for treatment failure was more often microbiologic failure in the daptomycin group (15.8% vs. 9.6%, p = 0.17) and more often due to an adverse event in the standard therapy group (14.8% vs. 6.7%, p = 0.06). There was no difference in survival at study end (85% for daptomycin vs. 84% for standard therapy, p = 0.98).


Among patients with Staphylococcus aureus bacteremia with or without endocarditis, treatment with daptomycin was noninferior with regard to treatment success compared with standard therapy with either vancomycin or an antistaphylococcal penicillin.


Fowler VG Jr, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 2006;355:653-65.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism

Keywords: Treatment Failure, Bacteremia, Floxacillin, Oxacillin, Vancomycin, Staphylococcus aureus, Daptomycin, Penicillins, Nafcillin, Endocarditis, Staphylococcal Infections, Methicillin Resistance, Confidence Intervals

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