Once-weekly dalbavancin versus daily conventional therapy for skin infection.
Author(s): Boucher HW(1), Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW.
Affiliation(s): Author information:
(1)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.).
Publication date & source: 2014, N Engl J Med. , 370(23):2169-79
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.).
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