An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection

Abstract

Background: Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers.

Methods: The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge.

Results: No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05).

Conclusion: This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI.

Trial registration: ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011).

Figures

Fig. 1

Mean inpatient costs by components. Drug cost calculation assumes waste of partial daptomycin vials. P = NS for all. Ward/unit cost was defined as the cost care in a particular unit or ward. Adjunctive procedures included incision/drainage, surgical debridement/excision, amputation, device removal/replacement, wound specialist services, and physical therapy. Radiology tests included radiography, medical resonance imaging, ultrasound, and computed tomography. WAC, wholesale acquisition cost

Fig. 2

Proportion of patients achieving clinical success by day 2 and day 3: overall (a), by infection type (b), and by pathogen (c). Clinical success was defined as improvement or cure. a Odds ratio (OR) for vancomycin compared with daptomycin. b Clinical success rates by infection type, excluding the 4 daptomycin and 4 vancomycin patients with “other” infection types. c Clinical success rates by pathogen, includr known S. aureus infection for those patients with a culture. MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus. See Table 3 for sample sizes