Linezolid antibacterial activity

The activity of daptomycin against both vancomycin-sensitive and vancomycin-resistant Enterococcus faecalis was greater than that of quinupristin + dalfopristin (5). Daptomycin was as active as quinupristin + dalfopristin but more active than linezolid. At concentrations four times the MIC, daptomycin and vancomycin achieved 99.9% killing of methicillin-resistant Staphylococcus aureus after 8 hours, which was greater than the killing seen with linezolid and quinupristin + dalfopristin. However, the antibacterial activity of daptomycin strongly depended on the calcium concentration of the medium. 

This new family of oxazolidinones was described and shown to effectively displace compounds that bind the ribosomal 50S A-site (linezolid site), including chloramphenicol and Puromycin [80]. The structures of several family members (16-20) are depicted in Scheme 3. The reader is referred to the primary citations for tables of antibacterial activity data (as is the case for all case studies). Compounds such as 17 and 19 were compounds predicted to have good oral bioavailability in the QSAR model [79]. Compounds such as 16 were predicted to have good Haemophilus influenzae activity in that QSAR activity model [79]. The computational and crystallographically inspired design of novel oxazolidinones eventually led to Rib-X Pharmaceuticals clinical candidate, Radezolid (20), currently in Phase II clinical trials [31]. 

It is disturbing to note that the only new class of antibacterial agents to appear during the past 30 years are the newly introduced oxazolidinones, of which linezolid and eperezolid are the first two examples - the former was approved in the USA (in 2000) and in the UK (Zyvox, in 2001). These emerged from work originally carried out by Dupont in the mid-1980s, which culminated in the discovery of the compound DUP 721. This had antibacterial activity but also possessed lethal toxicity in in vivo tests. Later... 

ANTIBACTERIAL ACTIVITY Because of its unique mechanism of action, linezolid is active against strains that are resistant to multiple other agents, including penicilhn-resistant strains of S. pneumoniae, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant strains of staphylococci and vancomycin-resistant strains of enterococci. 

Linezohd (Zyvox) is an oxazolidinone, a tive-membered heterocychc ring that forms the core of the hnezohd structure. The approval of hnezohd by the FDA in 2000 marked the first new structural class of antibacterial introduced into medical practice in the United States in 40 years. It is notable for its activity against methicillin-resistant Staph aureus, MRSA, and vancomycin-resistant Enterococcus faecium, VRE. It is bacteriostatic rather than bactericidal but finds significant use in patients with an intact immune system. Like several other classes of antibacterials, linezolid is an inhibitor of protein synthesis. It interacts specifically with the RNA component of a bacterial ribosome subunit to prevent initiation of protein synthesis. 

Some other drugs covered elsewhere also have MAOI aetivity. Furazolidone is an antiprotozoal with MAOI activity. Linezolid is an oxazolidi-none antibacterial with reversible nonseleetive MAOI activity. Interactions typical of MAOI inhibitors might therefore occur with furazolidone and linezolid. 

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