CLS07 - Antimicrobial Action/Resistance

  1. Antiobiotics vs Antimicrobial agents
    • Antibiotics: natural substances produced by microbial organisms, used to inhibit/kill bacteria
    • *now includes synthetic agents
    • Antimicrobial agents: natural and synthesized substances that inhibit/kill a target organism (virus, fungi, etc)
  2. Bacteriostatic vs Bactericidal
    • Bacteriostatic: inhibits growth
    • Bactericidal: kills organism
  3. Narrow spectrum vs broad spectrum antibiotics
    • Narrow spectrum: small group, specific type (G+)
    • Broad spectrum: includes more groups (Haeomphilus, other GNR, anaerobes)
  4. What is extended spectrum beta-lactamase?
    • Enzymes produced by G- to overcome antibiotics
    • Grants resistance to penicillins, carbapenem drugs
    • Plasmid-mediated (transferrable)
  5. What are the considerations for determining the proper antibiotic treatment?
    • Will the drug reach the target area?
    • Can it be concentrated at the site?
    • Will it kill or inhibit the organism?
    • Will it leave host cells unharmed?
  6. What are the BASIC antibiotic modes of action (Beta lactam, glycopeptide, polypeptide/lipopeptide, SXT, Quinolones, Aminoglycosides/macrolides, sulfonamides, trimethoprim)
    • Beta lactam, glycopeptide: inhibit cell wall synthesis
    • polypeptide/lipopeptides: inhibit cell membrane synthesis
    • SXT, Quinolones: inhibition of DNA synthesis
    • Aminoglycosides/macrolides: inhibition of protein synthesis
    • sulfonamides, trimethoprim: metabolic pathway inhibitors
  7. Beta-Lactam structure and function
    • four membered nitrogen-containing ring at core
    • bind enzyme inhibiting transpeptidation ∴ inhibit cell wall synthesis
    • cell wall weakened, leading to cell death
  8. Beta-lactam resistance
    • Production of enzymes (eg beta-lactamases)
    • 4 classes (Serine peptidases, Metallo-β-lactamases, cephalosporinases, serine peptidases)
    • break the beta-lactam ring
    • produce altered binding site (drug does not recognize)
  9. Beta-lactam examples + activity spectrum
    • Penicillins: penicillin, ampicillin, oxacillin
    • gram positive
    • Cephalosporins: multiple generations with increasing spectrum
    • broad, GNR
    • carbapenems: imipenem, meropenem
    • broad spectrum
  10. Glycopeptide structure and function
    • large structure (can't fit through G- LPS)
    • bind to the end of peptidoglycan, interfering with transpeptidation ∴ inhibit cell wall synthesis
  11. Cell membrane inhibitors function, last-resort drugs
    • Act like detergents interacting w/ phospholipids to increase permeability (good against G- LPS)
    • macromolecules/ions leak accross membrane
    • more effective against G-
    • Polymixin B and Colistin are last resort for P. aeruginosa and Acinetobacter
  12. Protein synthesis inhibitors function
    • Target protein synthesis and severely disrupt cellular metabolism
    • Bind 30S or 50S ribosomal subunits (not present in humans)
  13. Protein synthesis inhibitors examples
    • Aminoglycosides, aminocyclitols
    • marcolide-lincosamide-streptogramin group (MLS)
    • ketolides
    • oxazolidinones
    • chloramphenicol (DRUG OF CHOICE, LOW TOXICITY)
    • tetracyclines (low toxicity)
    • Glycylglycines (low toxicity)
  14. Fluoroquinolones function
    • bind to and interfere w/ DNA gyrase enzymes
    • newer quinolones inhibit topoisomerase IV
  15. metronidazole function
    • Nitro group is reduced in bacterial cytoplasm generating cytotoxic compounds that disrupt DNA
    • *poison is hidden w/ nitro group that is used by bacteria
  16. rifamycin function
    binds to DNA-dependent RNA polymeras and inhibits RNA synthesis
  17. sulfonamide function
    • inhibits dihydropteroate synthase in the folic acid pathway
    • *metabolic inhibitor
  18. trimethoprim function
    • inhibits dihydrofolate reductase in the folic acid pathway
    • *metabolic inhibitor
  19. nitrofuranitoin function
    • drug intermediates bind to bacteria ribosomal proteins and rRNA (not well understood)
    • *metabolic inhibitor
  20. Intrinsic vs acquired resistance
    • intrinsic: natural genetic make-up of WT organism
    • acquired: resistance after previous susceptibility
    • mutation, acquisition (plasmid)
  21. Describe various methods of intrinsic/acquired resistance
    • intrinsic
    • Cell wall permeability (eg. GNR resistant to glycopeptides)
    • efflux (pumped out)
    • biofilm formation (can't penetrate)
    • gene expression to inactivate antibiotic
    • acquired
    • modification to target site
    • enzyme inactivation of antibiotic
    • efflux
  22. 4 ways that resistance can emerge
    • New resistance genes
    • Spread of old resistance genes
    • Mutation of old resistance genes
    • Emergence of intrinsically resistant bacteria (Stenotrophomonas)
  23. What is mecA?
    • The gene that codes for altering of binding site in MRSA
    • Predicts resistance for all beta lactam drugs
    • can be detected by screeing plate/latex test
  24. What is inducible resistance?
    Erythromycin discs near clindamycin discs can induce resistance to clindamycin in an organism
Card Set
CLS07 - Antimicrobial Action/Resistance
CLS07 - Antimicrobial Action/Resistance