Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

Key Points A novel recombinant factor VIII with prolonged half-life, rFVIIIFc, was developed to reduce prophylactic injection frequency. rFVIIIFc was well-tolerated in patients with severe hemophilia A, and resulted in low bleeding rates when dosed 1 to 2 times per week.

Prophylactic rFIXFc, administered every 1 to 2 weeks, resulted in low annualized bleeding rates in patients with hemophilia B. (Funded by Biogen Idec; ClinicalTrials.gov number, NCT01027364.).

Daptomycin, a novel lipopeptide, is bactericidal against a broad range of gram-positive strains, including methicillin-(MRSA) and vancomycin-resistant Staphylococcus aureus. Daptomycin is approved at 4 mg/kg of body weight given intravenously once daily for the treatment of complicated skin and skin structure infections and at 6 mg/kg for the treatment of S. aureus bloodstream infections (bacteremia), including right-sided endocarditis caused by methicillin-susceptible S. aureus and MRSA. The present study was designed to evaluate the multiple-dose pharmacokinetics and safety of daptomycin at doses of 6 to 12 mg/kg in healthy volunteers. Three cohorts of 12 subjects each were given daptomycin (10 mg/kg) or placebo once daily for 14 days, daptomycin (12 mg/kg) or placebo once daily for 14 days, or daptomycin (6 or 8 mg/kg) once daily for 4 days. Daptomycin produced dose-proportional increases in the area under the plasma concentration-time curve and in trough daptomycin levels and nearly dose-proportional increases in peak daptomycin concentrations. Other pharmacokinetic parameters measured on day 1 and at steady state were independent of the dose, including the half-life (approximately 8 h), weight-normalized plasma clearance (9 to 10 ml/h/kg), and volume of distribution (approximately 100 ml/kg). Plasma protein binding was 90% to 93% and was independent of the daptomycin concentration. Daptomycin did not produce electrocardiographic abnormalities or electrophysiological evidence of muscle or nerve toxicity. Daptomycin was well tolerated in subjects dosed with up to 12 mg/kg intravenously for 14 days. Doses of daptomycin higher than 6 mg/kg once daily may be considered in further studies to evaluate the safety and efficacy of daptomycin in difficult-to-treat infections.Daptomycin is the first member of the novel cyclicallipopeptide class, which provides rapid, concentration-dependent bactericidal activity against a broad range of gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) (2, 6, 9, 10). Daptomycin causes bacterial cell death by a mechanism unique among available antimicrobial agents (8,11). It binds to the cell membranes of gram-positive bacteria, thereby disrupting their membrane potential, initiating potassium efflux with rapid cell death.The safety and efficacy of daptomycin in treating complicated skin and skin structure infections were demonstrated in two randomized, controlled clinical trials (1). When administered at a dose of 4 mg/kg of body weight intravenously once daily for 7 to 14 days, daptomycin provided clinical success rates comparable to those of vancomycin and penicillinaseresistant penicillins and showed safety and tolerability similar to those of the comparators. On the basis of these studies, daptomycin was approved by the FDA and the European Medicines Agency for the treatment of complicated skin and skin structure infections caused by susceptible gram-positive strains, including MRSA (3). Because of its antibacterial profile, daptomycin may also b...

Initial low-dose gentamicin as part of therapy for S. aureus bacteremia and native valve infective endocarditis is nephrotoxic and should not be used routinely, given the minimal existing data supporting its benefit.