Oritavancin: a novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains

Abstract

Oritavancin is a lipoglycopeptide antibiotic under investigation for the treatment of serious infections caused by Gram-positive bacteria. Oritavancin has demonstrated rapid dose-dependent bactericidal activity towards vancomycin-susceptible and -resistant enterococci, meticillin-susceptible and -resistant Staphylococcus aureus, vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), vancomycin-resistant S. aureus (VRSA) and small-colony variants of S. aureus. It is also active against Clostridium difficile. Upon intravenous administration, oritavancin displays a three-compartment pharmacokinetic model, dose proportionality, a distribution volume of ca. 110 L, a terminal elimination half-life in excess of 2 weeks and it is not metabolised. Its pharmacodynamic properties make it an ideal antibiotic for a once-daily or even single-dose regimen. Oritavancin is currently under review by the US Food and Drug Administration. So far, oritavancin has demonstrated efficacy in two pivotal Phase III trials conducted in patients with complicated skin and skin-structure infections in which oritavancin was compared with vancomycin plus cefalexin. In both trials, the primary endpoint (clinical cure in clinically evaluable patients at first follow-up with a 10% non-inferiority margin) was met, with the advantages of shorter duration of therapy and fewer adverse events. Further results indicating its activity against bacteria growing in biofilms as well as stationary-phase bacteria open the way for its use to treat prosthetic device infections, which is to be investigated in upcoming trials.