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  • Title: [Ketolides and oxazolidinones. Mechanisms of action and antibacterial spectrum].
    Author: Muller-Serieys C.
    Journal: Presse Med; 2000 Dec 02; 29(37):2061-4. PubMed ID: 11155736.
    Abstract:
    CHANGING RESISTANCE OF GRAM-POSITIVE COCCI: Several new families of antibiotics are under development in response to the changing resistance of Gram-positive cocci. Linezolide, the leading member of the oxazolidinone family and telithromycin and ABT-773, leading members of the ketolide family have reached an advanced stage of development. INHIBITION OF PROTEIN SYNTHESIS: Oxazolidinones and ketolides inhibit protein synthesis at different levels. Oxazolidinones inhibit formation of the 70S initiation complex and ketolides block the protein elongation step by inhibiting peptidyl transferase. MECHANISMS OF RESISTANCE: To date, no cross resistance of linezolide with other antibiotic families used for the treatment of Gram-positive bacteria has been observed. It is quite difficult to obtain resistant mutants in the laboratory but two point mutations on the 23S ribosome fraction have been described in vivo. Resistance of Gram-positive cocci to macrolides occur via mechanisms altering the target (methylation of 23S rRNA or ribosome protein mutations) or via mechanisms involving active efflux. LINEZOLIDE: Linezolide is highly active in vitro against meticillin-resistant Staphylococcus aureus (MRSA), against Streptococcus including resistant pneumococcal strains, and against glycopeptide-resistant E. faecium and E. faecalis strains. TELITHROMYCIN AND ABT-773: These ketolides are active against Streptococcus and Pneumococcus strains exhibiting erythromycin-inducible resistance and resistance by active efflux. In addition, these antibiotics are highly active against other bacteria causing respiratory tract infections (Moraxella and Haemophilus), anaerobic germs and intracellular germs (Legionella).
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