326Mantibio-clin - Antimicrobial agents Antibiotics Most...

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Antimicrobial agents- Antibiotics Most are used against bacteria; act at many different sites on the microbe (cell wall, chromosome, ribosomes); there are a few for fungi(amphotericin b; griseofulvin); antiviral agents are being developed ( α amantadine for influenza a, acyclovir for herpes simplex) The ideal antimicrobial agent: 1. Kills the organism selectively 2. Is not toxic or allergenic to host 3. Reaches effective concentration at appropriate site; concentration maintained at site 4. Is cost effective 5. Will not cause resistant microbes Antimicrobial Resistance- mechanisms microbes have to resist action of antibiotics; some are plasmid encoded (p); some are mainly chromosomal (c) THERE ARE 3 MAJOR RESISTANCE MECHANISMS: A. Preventing ACCESS to the TARGET site by inhibiting uptake or increasing export of antibiotic; e.g. tetracycline excretion in Gram + and - (p) B. TARGET MODIFICATION - e.g. (1) methylation of 23s rRNA in gram positives, makes ribosome resistant to macrolides (erythromycin) (p) (2) change in penicillin binding proteins (MRSA) (c) C. ENZYME PRODUCTION that inactivates drug; e.g. ß- lactamases made by Gram + and - degrade   penicillins (p)
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Antimicrobial Agent Action and Microbial Resistance (*) A. Cell wall action 1. β -lactams (penicillins,cephalosporins): inhibit final transpeptidation reaction in X-linking of peptidoglycan (Gr+,Gr-) 2. cycloserine (aa analogue): prevents first stage of murein synthesis (mainly mycobacteria) 3. vancomycin (glycopeptide): prevents 2nd stage of murein synthesis (Gr+) A*. Cell wall resistance (all 3 mechanisms) 1. β -lactams (penicillins,cephalosporins): β -lactamase production- destroys β -lactams (p,c) 2. alterations of penicillin binding proteins (PBP) (c) 3. permeability alterations (c) B. Outer and inner membrane action 1. polymyxin: cationic surfactant disrupts membrane (Gr-) B*. Membrane resistance: unknown acquired resistance mechanisms (c?) C. Protein synthesis inhibition (30S ribosomal subunit)
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This note was uploaded on 05/15/2010 for the course BIO 326M taught by Professor Field during the Spring '08 term at University of Texas.

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326Mantibio-clin - Antimicrobial agents Antibiotics Most...

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