Dalbavancin is an intravenous lipoglycopeptide with activity against Gram-positive pathogens and an MIC 90 for Staphylococcus aureus of 0.06 g/ml. With a terminal half-life of >14 days, dosing regimens with infrequent parenteral administration become available to treat infectious diseases such as osteomyelitis and endocarditis that otherwise require daily dosing for many weeks. In order to support a rationale for these novel regimens, the pharmacokinetics over an extended dosing interval and the distribution of dalbavancin into bone and articular tissue were studied in two phase I trials and pharmacokinetic modeling was performed. Intravenous administration of 1,000 mg of dalbavancin on day 1 followed by 500 mg weekly for seven additional weeks was well tolerated and did not demonstrate evidence of drug accumulation. In a separate study, dalbavancin concentrations in cortical bone 12 h after infusion of a single 1,000-mg intravenous infusion were 6.3 g/g and 2 weeks later were 4.1 g/g. A twodose, once-weekly regimen that would provide tissue exposure over the dalbavancin MIC for Staphylococcus aureus for 8 weeks, maximizing the initial exposure to treatment while minimizing the frequency of intravenous therapy, is proposed. Osteomyelitis is an infection of the bone associated with either hematogenous dissemination or direct inoculation as a consequence of trauma or infection from contiguous tissues. Its presentation may be either acute or chronic. The most common pathogen responsible for acute infection in adults is Staphylococcus aureus, with Pseudomonas aeruginosa, Serratia marcescens, and Escherichia coli also involved in traumatic infections and chronic presentations. Infection in children occurs less frequently and is predominantly a result of bacteremia with S. aureus and infection in the growth plate (1). Treatment regimens extend for 4 to 6 weeks, with durations as long as 8 weeks recommended for treatment of infection due to methicillin-resistant S. aureus (MRSA) (2). Commonly used therapies include cefazolin, oxacillin, or vancomycin for coverage of Gram-positive pathogens and cephalosporins, carbapenems, and the ␤-lactamase inhibitor agents for treatment of Gram-negative pathogens (2,3). No other therapies in recent times have received FDA approval.Because the incidence of MRSA in the community in the United States is as high as 40% (4), empirical treatment of osteomyelitis now requires consideration of antimicrobial coverage of this organism, typically with vancomycin. Vancomycin has been demonstrated to be active in animal models of osteomyelitis (5). Concentrations in bone from 2.7 to 9.3 g/ml have been documented (6, 7), exceeding the vancomycin MIC 90 for S. aureus of 1 g/ml (8). Because of the wide variety of underlying etiologies and comorbidities associated with osteomyelitis, it is difficult to generalize the rates of clinical success from clinical trials, but one study documented a clinical response in 10/15 patients after continuous intravenous (i.v.) infusion of vancomycin (9). Long-term d...

Dalbavancin when delivered as a single 1500-mg infusion is noninferior to the same total dose given as a 2-dose regimen, removing the logistical constraints related to the second dose while improving compliance and patient convenience.

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We thank all participants, investigators, and trial teams for their participation in the trial. The CREDENCE study was sponsored by Janssen Research & Development, LLC, and was conducted collaboratively by the sponsor, an academic-led Steering Committee, and an Academic Research Organization, George Clinical. Analyses were performed by George Clinical and independently confirmed by the sponsor. Technical editorial assistance was provided by Kimberly Dittmar, PhD, of MedErgy, and was funded by Janssen Global Services, LLC.