BOSTON—Daptomycin is well tolerated and effective for treating Staphylococcus aureus bacteremia (SAB) in patients with renal insufficiency but not on dialysis, new findings suggest.
Researchers presented findings from the ongoing CORE (Cubicin Outcomes Registry and Experience) study, which showed that the overall clinical success rate was 81%.
Investigators observed lower success rates for patients with a creatinine clearance below 30 mL/min compared with patients who had a creatinine clearance of 30-50 mL/min (70% vs. 94%), a finding consistent with other antimicrobial regimens.
Daptomycin is a lipopeptide antibiotic with bactericidal activity against methicillin-resistant S. aureus (MRSA) and other clinically relevant gram positive pathogens. It is approved by the FDA for the treatment of skin and skin structure infections (at a dose of 4 mg/kg) and for SAB, including right-sided endocarditis (at a dose of 6 mg/kg).
“Renal failure patients actually have a higher risk for invasive Staphylococcus aureus infections,” said lead author Pamela Moise, PharmD, a Clinical Scientific Director with Cubist Pharmaceuticals, Inc., in the Southern California Region. “However, the daptomycin registrational trials did not capture patients with renal insufficiency.” Dr. Moise presented study findings at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy.
The CORE study evaluated daptomycin in SAB management in non-dialysis patients with a creatinine clearance below 50 mL/min. From 2005 to 2009, 106 patients were enrolled. All were evaluable for safety, but only 80 (75%) were evaluable for efficacy. Among the 106 patients, 50 (47%) were female and 56 (53%) were male. Seventy-six (72%) of SAB cases were caused by MRSA.
In the current study, the median daptomycin dose was 6 mg/kg and the median duration of treatment was 11 days. The daptomycin dose was less than the recommended 6 mg/kg in 18 of the 59 patients (31%) with a creatinine clearance less than 30 mL/min and in seven of 47 patients (15%) with a creatinine clearance of 30-50 mL/min.
Four of the 106 patients experienced an adverse event or abnormal laboratory value possibly related to daptomycin, she said, adding that 2% of patients had an elevation in creatine phosphokinase.
Risk factors for invasive S. aureus disease include diabetes and renal failure, Dr. Moise said. These risk factors are becoming more prevalent in the United States because of the increasing obesity epidemic. Consequently, demand is growing for the development of novel, potent, and effective therapies for S. aureus disease.
“Although this is the largest study of daptomycin use for the management of S. aureus bacteremia in patients with a creatinine clearance of less than 50 mL/min,” Dr. Moise said, “we feel a larger study of this type may yield additional information.”