Helen W Boucher1, Mark Wilcox, George H Talbot, Sailaja Puttagunta, Anita F Das, Michael W Dunne. 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.).
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.).
RCT Entities:
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: Manu N Capoor; Jan Lochman; Andrew McDowell; Jonathan E Schmitz; Martin Solansky; Martina Zapletalova; Todd F Alamin; Michael F Coscia; Steven R Garfin; Radim Jancalek; Filip Ruzicka; A Nick Shamie; Martin Smrcka; Jeffrey C Wang; Christof Birkenmaier; Ondrej Slaby Journal: Eur Spine J Date: 2018-12-01 Impact factor: 3.134
Authors: John H Powers; Donald L Patrick; Marc K Walton; Patrick Marquis; Stefan Cano; Jeremy Hobart; Maria Isaac; Spiros Vamvakas; Ashley Slagle; Elizabeth Molsen; Laurie B Burke Journal: Value Health Date: 2017-01-10 Impact factor: 5.725
Authors: Abraham Pulido-Cejudo; Mario Guzmán-Gutierrez; Abel Jalife-Montaño; Alejandro Ortiz-Covarrubias; Jose Luis Martínez-Ordaz; Héctor Faustino Noyola-Villalobos; Luis Mauricio Hurtado-López Journal: Ther Adv Infect Dis Date: 2017-08-31
Authors: Michael W Dunne; Sailaja Puttagunta; Craig R Sprenger; Chris Rubino; Scott Van Wart; James Baldassarre Journal: Antimicrob Agents Chemother Date: 2015-01-05 Impact factor: 5.191