Linezolid inhibits translation at the first step of protein synthesis, initiation, unlike most other protein synthesis inhibitors, which inhibit elongation. It does so by preventing the formation of the initiation complex, composed of the 30S and 50S subunits of the ribosome, tRNA, and mRNA. Linezolid binds to the 23S portion of the 50S subunit (the center of peptidyl transferase activity), close to the binding sites of chloramphenicol, lincomycin, and other antibiotics. Due to this unique mechanism of action, cross-resistance between linezolid and other protein synthesis inhibitors is highly infrequent or nonexistent.In 2008, the crystal structure of linezolid bound to the 50S subunit of a ribosome from the archaean Haloarcula marismortui was elucidated by a team of scientists from Yale University and deposited in the Protein Data Bank. Another team in 2008 determined the structure of linezolid bound to a 50S subunit of Deinococcus radiodurans. The authors proposed a refined model for the mechanism of action of oxazolidinones, finding that linezolid occupies the A site of the 50S ribosomal subunit, inducing a conformational change that prevents tRNA from entering the site and ultimately forcing tRNA to separate from the ribosome. Pharmacokinetics
One of the advantages of linezolid is that it has an absolute oral bioavailability of 100% due to its rapid and complete absorption after oral administration; in other words, the entire dose reaches the bloodstream, as if it had been given intravenously.
The guidelines of the British Thoracic Society do not recommend it as first-line treatment, but rather as an alternative to vancomycin. Linezolid is also an acceptable second-line treatment for community-acquired pneumococcal pneumonia when penicillin resistance is present.U.S. guidelines recommend either linezolid or vancomycin as the first-line treatment for hospital-acquired (nosocomial) MRSA pneumonia. Some studies have suggested that linezolid is better than vancomycin against nosocomial pneumonia, particularly ventilator-associated pneumonia caused by MRSA, perhaps because the penetration of linezolid into bronchial fluids is much higher than that of vancomycin. Several issues in study design have been raised, however, calling into question results that suggest the superiority of linezolid. Regardless, linezolids advantages include its high oral bioavailability—which allows easy switching to oral therapy—and the fact that poor kidney function is not an obstacle to use. In contrast, achieving the correct dosage of vancomycin in patients with kidney failure is very difficult. Other
It is traditionally believed that so-called "deep" infections—such as osteomyelitis or infective endocarditis—should be treated with bactericidal antibiotics, not bacteriostatic ones. Nevertheless, preclinical studies were conducted to assess the efficacy of linezolid for these infections, and the drug has been used successfully to treat them in clinical practice. Linezolid appears to be a reasonable therapeutic option for infective endocarditis caused by multi-resistant Gram-positive bacteria, despite a lack of high-quality evidence to support this use. Results in the treatment of enterococcal endocarditis have varied, with some cases treated successfully and others not responding to therapy.