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Phase III Study: Once-Weekly Dalbavancin as Effective as Twice-Daily Vancomycin in Treating Bacterial Skin Infections

Authors see reduced need for hospital admission

A study published in the June 5 print edition of the New England Journal of Medicine reports that the antibiotic dalbavancin (Dalvance, Durata Therapeutics) is as effective as vancomycin, the current standard-of-care antibiotic used to treat serious bacterial skin and skin-structure infections (SSSIs). The study results establish dalbavancin as a therapy for Staphylococcus aureus infections, including methicillin-resistant S. aureus (MRSA).

On May 23, 2014, the FDA approved dalbavancin for the treatment of acute bacterial SSSIs in adults. These infections are among the most common reasons for the hospitalization of adults in the U.S. today, and the associated medical costs are substantial. In 2011, the Centers for Disease Control and Prevention (CDC) identified antimicrobial resistance as a serious U.S. and global health concern.

“Dalbavancin has a great likelihood of changing our practice in caring for patients with severe skin infections. It will now be possible to treat once a week instead of several times a day and will potentially remove the need for hospital admission and long-term intravenous catheters,” said lead investigator Helen Boucher, MD, of the Tufts Medical Center.

The researchers completed two phase III noninferioity trials — Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response (DISCOVER 1 and DISCOVER 2) — comparing the efficacy of dalbavancin with that of vancomycin followed by linezolid. The randomized, double-blind, double-dummy trials were conducted in 2011–2012.

For the studies, the diagnosis of an acute bacterial SSSI required the presence of cellulitis, a major abscess, or a wound infection, all with at least 75 square centimeters of surrounding redness. Additional diagnostic criteria included an elevated body temperature and an elevated white blood cell count.

The patients were given either once-weekly intravenous dalbavancin or twice-daily intravenous vancomycin followed by oral linezolid, along with dummy infusions or pills, for 10 to 14 days. The primary endpoint of both trials was an early clinical response, defined as the cessation of the spread of infection-related reddening and inflammation of the skin and the absence of fever at 48 to 72 hours. Secondary endpoints included the patient’s clinical status and the investigator’s assessment of outcome at the end of treatment.

The data from the two DISCOVER trials were pooled. An analysis showed that 79.7% (525/659) of the patients in the dalbavancin group and 79.8% (521/653) of those in the vancomycin/linezolid group experienced an early clinical response, indicating treatment success. For patients infected with S. aureus, including MRSA, clinical success was seen in 90.6% of the dalbavancin group and in 93.8% of the vancomycin/linezolid group.

Boucher explained: “The patients in our study were very ill. More than 85% had fever at entry, and more than half had systemic inflammatory response syndrome. In addition, our patients had large infections, with median areas of over 300 square centimeters. Our results establish dalbavancin as an effective therapy and prove non-inferiority of dalbavancin to vancomycin in the treatment of these serious infections.”

For the 6-month period of January to June 2010, a projected 9.2 million patients were treated in U.S. hospitals for infections of any type, and nearly 17% of the diagnostic category presentations were for SSSI. Of these presentations, approximately 74% were disease types included in acute bacterial SSSI. This category of infection increased by 176% from 1997 to 2009 in hospitalized patients. Most SSSIs in hospitalized patients are caused by S. aureus, and approximately 59% of these infections are estimated to be caused by MRSA in the U.S. Effective early treatment of acute bacterial SSSIs is critical to prevent wound expansion and to avoid lengthy and costly hospital stays.

Dalbavancin is a second-generation, semi-synthetic lipoglycopeptide consisting of lipophilic side-chains attached to glycopeptides. It is the only intravenous antibiotic approved for the treatment of acute bacterial SSSIs, with a two-dose regimen of 1,000 mg followed 1week later by 500 mg, each administered over 30 minutes. Dalbavancin has demonstrated bactericidal activity in vitro against a broad range of bacteria, such as S. aureus (including methicillin-resistant strains) and Streptococcus pyogenes, as well as certain other streptococcal species.

Sources: NEJM; June 5, 2014; Durata Therapeutics; June 4, 2014; and Medical Xpress; June 4, 2014.

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