Three new antibiotics to treat serious skin infections have been recommended for approval by the European Medicines Agency.
Orbactiv (oritavancin), Sivextro (tedizolid phosphate) and Xydalba (dalbavancin) are all indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) – a group of infections of the skin and surrounding tissues. ABSSSIs include cellulitis, erysipelas, wound infections and major abscesses, usually caused by Staphylococcus aureus or Streptococcus pyogenes. Skin lesions are the primary symptom, but ABSSSIs can cause systemic symptoms that can be serious and even life-threatening.
Oritavancin is a glycopeptide that works by disrupting bacterial membrane integrity, leading to rapid cell death. It is given as a single intravenous dose, a method that could be helpful in treating patients, such as intravenous drug users, for whom compliance with treatment is a problem.
Oritavancin was tested in two double-blind clinical trials of 976 patients treated with a single 1,200mg intravenous dose and 983 patients treated with intravenous vancomycin for 7 to 10 days.
Its results were non-inferior to vancomycin in reducing the size or spread of lesions and clinical cure rates. The most common side effects were nausea, hypersensitivity reactions, infusion site reactions and headache.
The other newly-recommended antibiotic, tedizolid phosphate, is an oxazolidinone antibiotic that works by binding to the 50S ribosomal subunit, thereby inhibiting protein biosynthesis in the bacterial cell.
Tedizolid is administered at a dose of 200mg daily for six days; it is available as a tablet or as a powder for concentrate for solution for infusion. Patients who start treatment on the parenteral formulation may be switched to the oral presentation when clinically indicated.
Tedizolid has been evaluated in two pivotal trials (ESTABLISH-1 and -2) involving 1,333 patients with ABSSSIs. In these trials, it was non-inferior to twice-daily linezolid 600mg for 10 days for the primary endpoint of early clinical response. The most common side effects were nausea, headache, diarrhoea and vomiting.
Orbactiv will be marketed by The Medicines Company UK Ltd while Sivextro will be marketed by Cubist (UK) Ltd. Pharmacovigilance plans for both drugs will be implemented as part of the marketing authorisation. They were both approved by the US Food and Drug Administration (FDA) in 2014.
The third antibiotic for skin and skin structure infections – dalbavancin – was recommended for approval by the EMA in December 2014.
Like oritavancin, dalbavancin is a glycopeptide antibiotic active against Gram-positive organisms. Dalbavancin was launched in the United States in 2014 following its approval by the US FDA.
In Europe, final approval for all three antibiotics from the European Commission is expected in 2015.