Radezolid Novel oxazolldinone Antibiotic

The oxazolidinones are a unique class of synthetic antibiotics, chemically distinct from any commercially available agent (45,136) The first oxazolidinones were reported in the late 1970s by researchers at E.I. Dupont de Nemours & Company (45,86) Further chemical modifications resulted in two 3-aryl-oxazolidinones compounds, DuP-721 and DuP-105, in 1987.

These agents demonstrated potent in vitro and in vivo activity versus a variety of antibiotic-susceptible and -resistant gram positive organisms (13,34,72,90,109) However, toxicity issues in animals led to the abandonment of further development of these compounds. Pharmacia Corporation (currently Pfizer, Inc.) revisited this class and examined hundreds of different oxazolidinone subclasses in an effort to find those with good antibacterial activity and low toxicity (134).

Two lead compounds, eperezolid (PNU-100592) and linezolid (PNU-100766), were selected for further study (20,22,136) Only linezolid continued beyond Phase I development, and is the first oxazalodinone approved for clinical use in more than 50 countries. AZD-2563 (AstraZeneca) is a newer oxazolidinone with a similar spectrum of activity to that of linezolid and completed phase I trials before it was discontinued in July 2002.

The oxazolidinones have several noteworthy attributes including 1) a novel mechanism of action, 2) a spectrum of activity that includes multidrug-resistant gram-positive bacteria, 3) excellent oral bioavailability, 4) difficulty in selecting resistance in vitro, and 5) lack of cross resistance with other antimicrobial agents