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Available from: Jose Miguel Sahuquillo-Arce, Sep 03, 2015
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    ABSTRACT: The oxazolidinones represent a novel chemical class of synthetic antimicrobial agents. They exhibit an unique mechanism of protein synthesis inhibition and generally display bacteriostatic activity against many important human pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Linezolid, the oxazolidinone which has been selected for clinical development, has near complete oral bioavailability plus favourable pharmacokinetic and toxicity profiles. Results from experimental models of infection and phase II trials reveal linezolid to be highly active in vivo against infections due to many common gram-positive pathogens. The role of linezolid remains to be determined in phase III clinical trials, but it shows great promise as an alternative to glycopeptides and streptogramins to treat serious infections due to resistant gram-positive organisms. Further modification of the oxazolidinone nucleus may yield agents with even greater potency and with novel spectra of activity.
    Drugs 02/2000; 59(1):7-16. · 4.34 Impact Factor
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    ABSTRACT: The oxazolidinones represent a new class of antimicrobial agents which are active against multidrug-resistant staphylococci, streptococci, and enterococci. Previous studies have demonstrated that oxazolidinones inhibit bacterial translation in vitro at a step preceding elongation but after the charging of N-formylmethionine to the initiator tRNA molecule. The event that occurs between these two steps is termed initiation. Initiation of protein synthesis requires the simultaneous presence of N-formylmethionine-tRNA, the 30S ribosomal subunit, mRNA, GTP, and the initiation factors IF1, IF2, and IF3. An initiation complex assay measuring the binding of [3H]N-formylmethionyl-tRNA to ribosomes in response to mRNA binding was used in order to investigate the mechanism of oxazolidinone action. Linezolid inhibited initiation complex formation with either the 30S or the 70S ribosomal subunits from Escherichia coli. In addition, complex formation with Staphylococcus aureus 70S tight-couple ribosomes was inhibited by linezolid. Linezolid did not inhibit the independent binding of either mRNA or N-formylmethionyl-tRNA to E. coli 30S ribosomal subunits, nor did it prevent the formation of the IF2-N-formylmethionyl-tRNA binary complex. The results demonstrate that oxazolidinones inhibit the formation of the initiation complex in bacterial translation systems by preventing formation of the N-formylmethionyl-tRNA-ribosome-mRNA ternary complex.
    Antimicrobial Agents and Chemotherapy 01/1999; 42(12):3251-5. · 4.48 Impact Factor
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    ABSTRACT: The oxazolidinones are a new synthetic class of antimicrobials structurally unrelated to any agent presently marketed. Data pertaining to these compounds, with respect to their pharmacology, pharmacokinetics, pharmacodynamics, mechanism of action, and bacteriologic activity, focusing on the analogs linezolid (PNU 100766) and eperezolid (PNU 100592), were retrieved by MEDLINE search and review of relevant abstracts presented at recent clinical conferences. Since the drugs are still investigational, we obtained in vitro and animal data as well as available human studies. The oxazolidinones have bacteriostatic activity against a number of important pathogens including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci. They appear to be efficacious and well tolerated both orally and parenterally. Their role remains to be elucidated by clinical trials.
    Pharmacotherapy 05/1998; 18(3):456-62. DOI:10.1002/j.1875-9114.1998.tb03109.x · 2.66 Impact Factor
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