Safety and Efficacy of Daptomycin in the Treatment of Osteomyelitis: Results from the CORE^®Registry

Abstract

Antibiotic safety is a major determinant in osteomyelitis therapy. Limited data is available describing the long-term safety and efficacy of daptomycin. the safety population was drawn from CORE 2005 and 2006, a retrospective, observational, multicenter study. Clinically evaluable patients received >3 days of daptomycin appropriately adjusted for renal function. three hundred twenty-seven patients were evaluated for safety; 188 (57%) >or=6 mg/kg, 139 (43%) <6 mg/kg. Thirty-one (10%) patients experienced adverse events possibly related to daptomycin and the incidence was similar regardless of dose. No difference was observed in the rate of creatine phosphokinase elevations by dose. A trend toward higher improved rates was noted in patients receiving a final dose of >or=6mg/kg (96% vs. 90%, P=0.08). Daptomycin appeared well-tolerated at doses of 6 mg per kg or greater which were associated with greater clinical improvement. These results require verification via a prospective clinical trial.

Randomized Controlled Trial of the Safety and Efficacy of Daptomycin versus Standard-of-Care Therapy for Management of Patients with Osteomyelitis Associated with Prosthetic Devices Undergoing Two-Stage Revision Arthroplasty

“…Although the increases in CPK observed with both the 6-and 8-mg/kg doses of daptomycin in this study were numerically higher than those seen with the comparator group, they are consistent with other clinical trials of daptomycin at Ն6 mg/kg, where 2.5% to 8.3% of patients experienced CPK elevations (6,9,11,14). Most CPK elevations in our study were of short duration and did not result in musculoskeletal symptoms.…”

Towards a definition of daptomycin optimal dose: Lessons learned from experimental and clinical data

“…In the Cubicin Outcome Register and Experience (CORE), <6 mg/kg vs. ≥6 mg/kg daily doses have been compared in patients treated for osteoarticular infections mostly due to S. aureus in, respectively, 139 and 188 patients. No significant differences in terms of clinical efficacy (90% vs. 96%, respectively) were observed [58]. In the European CORE (EUCORE) study, similar results were found in patients treated for osteomyelitis with 6.2-8 mg/kg [success rate, 82% (23/28)] and 4-6.2 mg/kg and [success rate, 75% (130/174)] [59].…”

Evaluation of Daptomycin Exposure and Efficacy and Safety Endpoints To Support Risk-versus-Benefit Considerations

“…The lack of an impressive change in the mean probabilities of clinical success and decreased susceptibility was expected, as the daptomycin AUC and, thus, dose would need to more than double (e.g., the dose would need to increase from 6 to 12 mg/kg/day) to provide exposures adequate to cover a 1-dilution increase in the MIC. Increasing numbers of reports and amounts of data from clinical studies provide support for the use of higher doses of daptomycin (8 to 12 mg/kg/day) to improve outcomes among patients with serious and life-threatening infections (21)(22)(23)(24)(25)(26). The results of simulations conducted to evaluate the mean probabilities of favorable outcomes with daptomycin at 8 and 10 mg/kg/day should be interpreted with some caution since the exposures and model-predicted probabilities estimated were at or beyond those for the exposure range studied; thus, some degree of extrapolation was required.…”