Clinical outcomes of patients receiving daptomycin for the treatment of Staphylococcus aureus infections and assessment of clinical factors for daptomycin failure: a retrospective cohort study utilizing the Cubicin Outcomes Registry and Experience.
BACKGROUND
Daptomycin is most commonly used as a second-line treatment. Previous studies have not differentiated the effect of prior antibiotic therapy on daptomycin clinical outcomes.


OBJECTIVE
The primary objective of this study was to compare clinical outcomes of patients treated with daptomycin as first-line therapy versus after prior antibiotic therapy (specifically, vancomycin). A secondary objective was to identify other factors associated with the clinical failure of daptomycin therapy.


METHODS
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.
Division of Infectious Diseases, New York Medical College, Valhalla, New York, USA. george.sakoulas@sharp.com
George
G
Sakoulas
Jack
J
Brown
Kenneth C
KC
Lamp
Lawrence V
LV
Friedrich
Kimberly C
KC
Lindfield
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D017576:Daptomycin / Q000627:therapeutic use*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012042:Registries; D012044:Regression Analysis; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017576:Daptomycin