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There are limited therapeutic options to treat infections caused by vancomycin-resistant Enterococcus faecium (VREfm). The lipoglycopeptide oritavancin exhibits in vitro activity against this pathogen, although its utility against infections caused by VREfm has not been clinically established. In this study, the pharmacodynamic activity of free-drug levels associated with 12 mg/kg/day of daptomycin and a single 1,200-mg dose of oritavancin were determined against three VanA VREfm isolates in an in vitro pharmacokinetic/pharmacodynamic model., (Copyright © 2017 American Society for Microbiology.)

Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The phase 3 studies SOLO I and SOLO II demonstrated comparable efficacy and safety of a single dose of oritavancin compared with 7-10 days of twice-daily vancomycin in adults with acute bacterial skin and skin-structure infections (ABSSSIs). The present analysis assessed clinical responses by pathogen at 48-72 h and at study days 14-24 in SOLO patients within the pooled data set. Of the 1959 patients in the pooled SOLO studies, 1067 had at least one baseline Gram-positive pathogen and 405 had MRSA. Clinical response rates were similar for oritavancin- and vancomycin-treated patients by pathogen, including Staphylococcus aureus with or without the Panton-Valentine leukocidin (pvl) gene and from different clonal complexes, and were similar for pathogens within each treatment group. Oritavancin exhibited potent in vitro activity against all baseline pathogens, with MIC 90 values (minimum inhibitory concentration required to inhibit 90% of the isolates) of 0.12 µg/mL for Staphylococcus  aureus, 0.25 µg/mL for Streptococcus pyogenes and 0.06 µg/mL for Enterococcus faecalis. Whereas both oritavancin and vancomycin achieved similarly high rates of clinical response by pathogen, including methicillin-susceptible and -resistant Staphylococcus aureus, oritavancin provides a single-dose alternative to 7-10 days of twice-daily vancomycin to treat ABSSSIs., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: Oritavancin is a lipoglycopeptide antibiotic with rapid bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and long half-life allow for single-dose treatment., Methods: In a randomized, double-blind trial, adults with acute bacterial skin and skin structure infections (ABSSSIs) received either a single intravenous 1200-mg dose of oritavancin or 7-10 days of twice-daily vancomycin. Three efficacy endpoints were tested for noninferiority: (1) primary composite endpoint at 48-72 hours (cessation of spreading or reduction in lesion size, absence of fever, and no rescue antibiotic); (2) investigator-assessed clinical cure 7-14 days after end of treatment; and (3) ≥20% reduction in lesion area at 48-72 hours., Results: A total of 503 and 502 patients comprised the modified intent-to-treat population for oritavancin and vancomycin, respectively. All 3 efficacy endpoints met the 10% noninferiority margin: the primary composite endpoint (80.1% vs 82.9%; 95% confidence interval [CI], -7.5 to 2.0), investigator-assessed clinical cure (82.7% vs 80.5%; 95% CI, -2.6 to 7.0), and proportion of patients attaining ≥20% reduction in lesion area (85.9% vs 85.3%; 95% CI, -3.7 to 5.0) for oritavancin vs vancomycin, respectively. Efficacy outcomes by pathogen, including methicillin-resistant Staphylococcus aureus and the frequency of adverse events, were similar between treatment groups., Conclusions: A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens, and was well tolerated. Oritavancin provides a single-dose alternative to multidose therapies for the treatment of ABSSSIs. Clinical Trials Registration. NCT01252732., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

A letter to the editor is presented which discusses the in vitro activity of oritavancin and other lipoglycopeptides against vancomycin-susceptible and -resistant Enterococcus faecalis.