Linezolid:U-100766

Linezolid (previously U-100766) is the first in a new class of completely synthetic antimicrobial agents, the oxazolidinones. It was approved for clinical use in the USA in April 2000 after a priority review by the US Food and Drug Administration (FDA). Initial indications for therapy included vancomycin-resistant Enterococcus faecium infection, nosocomial pneumonia, and complicated skin and skin structure infection. The E I du Pont de Nemours company developed the early oxazolidinones in the late 1980s; however, toxicity prevented further development. 

Linezolid, a (S)-5-acetamidomethyl-2 derivative, was later developed by Upjohn (later Pharmacia and Upjohn) and was released for clinical use after phase I clinical trials demonstrated no major toxic effects. 

Pfizer now markets linezolid under the trade name Zyvoxs. It is available as an intravenous suspension for injection, and as tablets and liquid suspension for oral administration. The oxazolidinones have a unique mechanism of action to inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit, thereby precluding cross-resistance with other currently available antimicrobial agents. 

Linezolid has activity against all major Grampositive pathogens of humans (including staphylococci, enterococci, streptococci, Bacillus species, Corynebacterium, and Listeria monocytogenes), good activity against many Gram-positive anaerobes, and activity against a number of mycobacteria and Nocardia species. Linezolid has no useful clincial activity against Gram-negative bacteria. Linezolid has been used primarily for treatment of resistant Gram-positive infections; however, hematologic and neurologic toxicity related to inhibition of mitochondrial protein synthesis has become an issue, particularly with prolonged therapy.