This was a retrospective cohort study using data from a postlabeling registry database. The effects of relevant patient characteristics on the clinical outcome of individuals treated for
Staphylococcus aureus infections with
daptomycin were examined in an unblinded approach using univariate and multivariate analyses. Only patients with an evaluable clinical outcome (ie, cure, improvement, failure) and culture-confirmed S aureus
infection were included in the analysis cohort.
RESULTS: Of 1227 clinically evaluable patients, 250 (20%) received
daptomycin as first-line
therapy and 977 (80%) received
daptomycin after other prior
antibiotic therapy. Overall, 53% of patients were male; 64% were aged 31 to 65 years and 26% were aged >or=66 years. Race information was collected beginning in 2007; of the patients studied, 71% were white and 18% were black. The initial
daptomycin dose (mean [SD]) overall was 5.1 (1.1) mg/kg and was highest for patients with
endocarditis (5.9 [1.2] mg/kg) and lowest for those with uncomplicated skin and skin structure
infections (4.4 [0.9] mg/kg). Clinical success, defined as an outcome of cured or improved at the end of
daptomycin therapy, was reported for 1140 (93%) of the 1227 evaluable patients. The clinical success rates for first-line
therapy with
daptomycin and after prior
antibiotics were both 93%. Using univariate analysis, 8 variables were associated with clinical failure (receipt of
daptomycin in an intensive care unit setting, severe renal dysfunction [
creatinine clearance <30 mL/min], dialysis,
diabetes mellitus (DM), concomitant
antibiotics,
bacteremia,
endocarditis, and failure of prior
vancomycin therapy) and 3 with clinical success (outpatient
daptomycin therapy and complicated and uncomplicated skin and skin structure
infections). Using the stepwise multivariate regression analysis, only the presence of
endocarditis (odds ratio [OR] = 2.56; 95% CI, 1.18-5.54; P = 0.017),
bacteremia (OR = 1.77; 95% CI, 1.04-3.02; P = 0.037), severe renal dysfunction (OR = 1.78; 95% CI, 1.05-3.03; P = 0.034), and DM (OR = 1.79; 95% CI, 1.10-2.93; P = 0.02) were identified as factors independently associated with clinical failure of
daptomycin therapy. Of the remaining patients, 9% were aged 18 to 30 years and 0.7% were aged 12 to 17 years.
CONCLUSIONS: In this retrospective study, after controlling for clinical factors that are associated with suboptimal outcomes, clinical outcomes with
daptomycin did not differ whether it was used as first-line
therapy or after other
antibiotics.
Endocarditis,
bacteremia, severe renal dysfunction, and DM were associated with higher rates of clinical failure of
daptomycin treatment.