The oxazolidinones as a new family of antimicrobial agent

Abstract

The oxazolidinones are a new chemical class of synthetic antimicrobials characterized by a unique mechanism of protein synthesis inhibition. Linezolid is the first compound of this class and has recently received approval for the treatment of community- and hospital-acquired pneumonia and skin and skin structure infections. In vitro tests demonstrate that linezolid possesses a significant activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), vancomycin-intermediate strains (VISA) and penicillin-resistant pneumococci (PRPN). Combined with other drugs linezolid interacts favourably against many important pathogens and it is able to affect some bacterial virulence factors as well as produce a postantibiotic effect. Results from experimental models of infection reveal linezolid to be highly active in vivo against infections due to Gram-positive pathogens. Linezolid may be administered either intravenously or orally with oral bioavailability of approximately 100% and limited adverse effects. The clinical efficacy of linezolid has been investigated in several phase II and III trials. Linezolid has been proved to be useful in severe infections sustained by multiresistant Gram-positive micro-organisms. Synthesis of the second-generation oxazolidinones with improved potency against Gram-positive and negative bacteria is currently under way.