sharon sanders
Editor-in-Chief & President
ORIGINAL ARTICLE
Single-Dose Oritavancin in the Treatment of Acute Bacterial Skin Infections
G. Ralph Corey, M.D., Heidi Kabler, M.D., Purvi Mehra, M.D., Sandeep Gupta, M.D., J. Scott Overcash, M.D., Ashwin Porwal, M.D., Philip Giordano, M.D., Christopher Lucasti, M.D., Antonio Perez, M.D., Samantha Good, Ph.D., Hai Jiang, Ph.D., Greg Moeck, Ph.D., and William O'Riordan, M.D. for the SOLO I Investigators
N Engl J Med 2014; 370:2180-2190June 5, 2014DOI: 10.1056/NEJMoa1310422
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BACKGROUND
Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and prolonged half-life allow for single-dose treatment.
METHODS
We conducted a randomized, double-blind trial in which adults with acute bacterial skin and skin-structure infections received either a single intravenous dose of 1200 mg of oritavancin or a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy end points were tested for noninferiority. The primary composite end point was defined as cessation of spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic 48 to 72 hours after administration of oritavancin. Secondary end points were clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator, and a reduction in lesion size of 20% or more 48 to 72 hours after administration of oritavancin.
RESULTS
The modified intention-to-treat population comprised 475 patients who received oritavancin and 479 patients who received vancomycin. All three efficacy end points met the prespecified noninferiority margin of 10 percentage points for oritavancin versus vancomycin: primary end point, 82.3% versus 78.9% (95% confidence interval [CI] for the difference, −1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95% CI for the difference, −5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for the difference, −0.5 to 8.6 percentage points). Efficacy outcomes measured according to type of pathogen, including methicillin-resistant Staphylococcus aureus, were similar in the two treatment groups. The overall frequency of adverse events was also similar, although nausea was more common among those treated with oritavancin.
CONCLUSIONS
A single dose of oritavancin was noninferior to twice-daily vancomycin administered for 7 to 10 days for the treatment of acute bacterial skin and skin-structure infections caused by gram-positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov number, NCT01252719.)
http://www.nejm.org/doi/full/10.1056/NEJMoa1310422?query=featured_home&
Single-Dose Oritavancin in the Treatment of Acute Bacterial Skin Infections
G. Ralph Corey, M.D., Heidi Kabler, M.D., Purvi Mehra, M.D., Sandeep Gupta, M.D., J. Scott Overcash, M.D., Ashwin Porwal, M.D., Philip Giordano, M.D., Christopher Lucasti, M.D., Antonio Perez, M.D., Samantha Good, Ph.D., Hai Jiang, Ph.D., Greg Moeck, Ph.D., and William O'Riordan, M.D. for the SOLO I Investigators
N Engl J Med 2014; 370:2180-2190June 5, 2014DOI: 10.1056/NEJMoa1310422
Share:
BACKGROUND
Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and prolonged half-life allow for single-dose treatment.
METHODS
We conducted a randomized, double-blind trial in which adults with acute bacterial skin and skin-structure infections received either a single intravenous dose of 1200 mg of oritavancin or a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy end points were tested for noninferiority. The primary composite end point was defined as cessation of spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic 48 to 72 hours after administration of oritavancin. Secondary end points were clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator, and a reduction in lesion size of 20% or more 48 to 72 hours after administration of oritavancin.
RESULTS
The modified intention-to-treat population comprised 475 patients who received oritavancin and 479 patients who received vancomycin. All three efficacy end points met the prespecified noninferiority margin of 10 percentage points for oritavancin versus vancomycin: primary end point, 82.3% versus 78.9% (95% confidence interval [CI] for the difference, −1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95% CI for the difference, −5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for the difference, −0.5 to 8.6 percentage points). Efficacy outcomes measured according to type of pathogen, including methicillin-resistant Staphylococcus aureus, were similar in the two treatment groups. The overall frequency of adverse events was also similar, although nausea was more common among those treated with oritavancin.
CONCLUSIONS
A single dose of oritavancin was noninferior to twice-daily vancomycin administered for 7 to 10 days for the treatment of acute bacterial skin and skin-structure infections caused by gram-positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov number, NCT01252719.)
http://www.nejm.org/doi/full/10.1056/NEJMoa1310422?query=featured_home&