title: Once-weekly dalbavancin versus daily conventional therapy for skin infection.
abstract: BACKGROUND
  Dalbavancin, a lipoglycopeptide antibiotic agent that is active against gram-positive pathogens, has a long plasma half-life, allowing for once-weekly dosing. DISCOVER 1 and DISCOVER 2 were identically designed noninferiority trials of dalbavancin for the treatment of acute bacterial skin and skin-structure infection.
  
  
  METHODS
  We randomly assigned patients to receive dalbavancin intravenously on days 1 and 8 or vancomycin intravenously for at least 3 days with the option to switch to oral linezolid to complete 10 to 14 days of therapy. The primary end point, early clinical response, required the cessation of spread of infection-related erythema and the absence of fever at 48 to 72 hours. Secondary end points at the end of therapy included clinical status and investigator's assessment of outcome.
  
  
  RESULTS
  Analysis of the primary end point showed noninferiority of dalbavancin in both DISCOVER 1 and DISCOVER 2. In the pooled analysis, 525 of 659 patients (79.7%) in the dalbavancin group and 521 of 653 (79.8%) in the vancomycin-linezolid group had an early clinical response indicating treatment success (weighted difference, -0.1 percentage point; 95% confidence interval, -4.5 to 4.2). The outcomes were similar in the analyses by study and the pooled analyses of clinical status at the end of therapy and the investigator's assessment of outcome. For patients infected with Staphylococcus aureus, including methicillin-resistant S. aureus, clinical success was seen in 90.6% of the patients treated with dalbavancin and 93.8% of those treated with vancomycin-linezolid. Adverse events and study days with an adverse event were less frequent in the dalbavancin group than in the vancomycin-linezolid group. The most common treatment-related adverse events in either group were nausea, diarrhea, and pruritus.
  
  
  CONCLUSIONS
  Once-weekly intravenous dalbavancin was not inferior to twice-daily intravenous vancomycin followed by oral linezolid for the treatment of acute bacterial skin and skin-structure infection. (Funded by Durata Therapeutics; DISCOVER 1 and DISCOVER 2 ClinicalTrials.gov numbers, NCT01339091 and NCT01431339.).
authors.affiliation: From the Division of Infectious Diseases and Geographic Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston (H.W.B.); the Department of Microbiology, Leeds Teaching Hospital and University of Leeds, Old Medical School, Leeds, United Kingdom (M.W.); Talbot Advisors, Anna Maria, FL (G.H.T.); Durata Therapeutics, Branford, CT (S.P., M.W.D.); and InClin, San Mateo, CA (A.F.D.).
authors.forename: Helen W
authors.initials: HW
authors.lastname: Boucher
authors.forename: Mark
authors.initials: M
authors.lastname: Wilcox
authors.forename: George H
authors.initials: GH
authors.lastname: Talbot
authors.forename: Sailaja
authors.initials: S
authors.lastname: Puttagunta
authors.forename: Anita F
authors.initials: AF
authors.lastname: Das
authors.forename: Michael W
authors.initials: MW
authors.lastname: Dunne
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects; D017192:Skin Diseases, Bacterial / Q000188:drug therapy*; D017334:Teicoplanin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D017334:Teicoplanin; D014640:Vancomycin; C469289:dalbavancin; D000069349:Linezolid