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Antibacterial susceptibility testing

Antibacterial susceptibility testing. Drug classes Methods for testing Laboratory strategies. Basic principles of antimicrobial action. 1. Agent is in active form - pharmacodynamics: structure & route 2. Achieve sufficient levels at site of infection - pharmacokinetics.

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Antibacterial susceptibility testing

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  1. Antibacterial susceptibility testing

  2. Drug classes Methods for testing Laboratory strategies

  3. Basic principles of antimicrobial action 1. Agent is in active form - pharmacodynamics: structure & route 2. Achieve sufficient levels at site of infection - pharmacokinetics

  4. Anatomic distribution Serum CSF Urine Ampicillin + + + Ceftriaxone + + + Vancomycin + ± + Ciprofloxacin + ± + Gentamicin + - + Clindamycin + - - Norfloxacin - - + Nitrofurantoin - - +

  5. Basic principles of antimicrobial action • 3. Adsorption of drug by organism • 4. Intracellular uptake • 5. Target binding • Growth inhibition (bacteriostatic) • or death (bactericidal) • - Resistance can develop at any point

  6. Mechanisms of action Beta-lactams Penicillins, cephalosporins, carbapenems Inhibit cell wall synthesis by binding PBPs Active against many Gram + and Gram – (varies) Aminoglycosides Gentamicin, tobramycin, amikacin, streptomycin Inhibit protein synthesis (30S ribosomal subunit) Gram + and Gram – but not anaerobes

  7. Beta-lactams http://www.life.umd.edu/classroom/bsci424/Definitions.htm

  8. Aminoglycosides http://gsbs.utmb.edu/microbook/ch011.htm

  9. Mechanisms of action Fluoroquinolones Ciprofloxacin, levofloxacin Inhibit DNA synthesis by binding to gyrases Active against many Gram + and Gram – (varies) Glycopeptides Vancomycin Inhibit cell wall synthesis by binding precursors Gram + only

  10. Quinolones Glycopeptide http://gsbs.utmb.edu/microbook/ch011.htm

  11. Mechanisms of action Macrolides-lincosamides Erythromycin, azithromycin, clindamycin Inhibit protein synthesis (50S ribosomal subunit) Most Gram + and some Gram – Tetracyclines Tetracycline, doxycycline Inhibit protein synthesis (30S ribosomal subunit) Gram + and Gram – and intracellular orgs.

  12. Macrolides Tetracycline http://gsbs.utmb.edu/microbook/ch011.htm

  13. Mechanisms of action Oxazolidinones Linezolid Inhibit protein synthesis (50S ribosomal subunit) Gram + and Gram – including multi-resistant Streptogramins Quinupristin/dalfopristin (Synercid) Inhibit protein sythesis (50S ribosomal subunit) Primarily Gram + organisms

  14. Linezolid Streptogramins http://www.kcom.edu/faculty/chamberlain/Website/Lects/Metabo.htm

  15. Mechanisms of action Trimethoprim Sulfonamides Usually combined (Trimeth/sulfa) Inhibit different parts of folic acid pathway affects DNA synthesis Gram + and many Gram –

  16. http://gsbs.utmb.edu/microbook/ch011.htm

  17. Mechanisms of resistance Biologic - physiologic changes resulting in a decrease in susceptibility Clinical - physiologic changes have progressed to a point where drug is no longer clinically useful

  18. Mechanisms of resistance Environmentally-mediated Physical or chemical characteristics that alter the agent or the organism’s physiologic response to the drug pH anaerobiasis cations metabolites

  19. Mechanisms of resistance Microorganism-mediated Intrinsic  predictable Gram neg vs. vancomycin (uptake) Klebsiella vs. ampicillin (AmpC) Aerobes vs. metronidazole (anaerobic activation)

  20. Mechanisms of resistance Microorganism-mediated Acquired  unpredictable - this is why we test - mutations, gene transfer, or combination

  21. Mechanisms of resistance These factors are taken into account to attempt to standardize in vitro testing methods. In vitro methods are not designed to recreate in vivo physiology. In vivo physiology affects clinical response such that in vitro testing cannot be used to predict clinical outcome.

  22. Mechanisms of resistance • Common pathways • Enzymatic degradation or modification of agent • Decreased uptake or accumulation of agent • Altered target • Circumvention of consequences of agent • Uncoupling of agent-target interactions • Any combination of above

  23. Selective pressure from excessive antimicrobial use and abuse Mixing of bacterial gene pool Emergence of resistance Survival of the fittest

  24. Emergence of resistance • 1. Emergence of new genes • - MRSA, VRE, GISA • 2. Spread of old genes to new hosts • - Pen resistant GC , GRSA • 3. Mutations of old genes resulting in more potent resistance • - ESBLs • 4. Emergence of intrinsically resistant opportunistic bacteria • - Stenatrophomonas

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