DISCOVER 1 and DISCOVER 2 are identically designed noninferiority studies. 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. The studies are two of three phase III, randomised, double-blind clinical trials reported in the New England Journal of Medicine evaluating antibiotic treatment (the other study involved oritavancin) of acute bacterial skin and skin-structure infections.
Dalbavancin and oritavancin are semisynthetic lipoglycopeptide analogues of teicoplanin and vancomycin, respectively, all of which share a similar mechanism of action and spectrum of activity. Both of these agents have terminal half-lives of approximately 2 weeks, and serum free-drug concentrations exceed MICs for a week or more. The clinical trials of dalbavancin and oritavancin were designed to take advantage of these properties by administering one or two large, pulse doses instead of smaller, closely spaced, multiple doses. Neither antibiotic was found to be more efficacious than vancomycin, but either agent was easier to administer this making it possible to treat patients with complicated skin and skin-structure infections, who might otherwise require hospitalisation, on an outpatient basis without compromising efficacy and without the need for laboratory monitoring or an indwelling intravenous catheter. This approach has the potential to reduce or in some cases eliminating costs and risks of hospitalisation.
The efficacy of these antibiotics for infections other than complicated acute bacterial skin and skin-structure infections is unknown, and although their safety profiles in patients treated thus far are similar to that of vancomycin, confirmation is required from broader clinical use. It is of concern that once administered, these drugs take weeks to clear; and moderate or severe toxic or allergic reactions, if they occur, could cause substantial morbidity or prove fatal.
In January 2014, the European Medicines Agency accepted for review a marketing authorisation application for dalbavancin for the treatment of patients with complicated skin and soft tissue infections caused by susceptible gram-positive microorganisms.