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Antimicrobial Drugs

Antimicrobial Drugs. The dawn of antibiotics. Paul Erlich (1910) Wanted to find the “ magic bullet ” for syphilis proposed the idea of the blood brain barrier Worked at staining tissues and first to come up with the idea behind “ selective toxicity ” Nobel Prize in 1908.

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Antimicrobial Drugs

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  1. Antimicrobial Drugs

  2. The dawn of antibiotics • Paul Erlich (1910) • Wanted to find the “magic bullet” for syphilis • proposed the idea of the blood brain barrier • Worked at staining tissues and first to come up with the idea behind “selective toxicity” • Nobel Prize in 1908

  3. Alexander Fleming • A physician who studied bacterial action of blood and antisepsis • Discovered and named Lysozyme • Discovered mold growing on an agan plate(1928) • 1945 Nobel Prize in Physiology or Medicine along with Chain and Florey

  4. Chain and Florey • 1940 developed a system for growing Penicillium and purifying the drug • Tested the drug in mice, passed all trials • Received the Nobel Prize in 1945 with Alexander Fleming for their work

  5. Antibiotics • A substance produced by a microorganism that inhibits or kills other microbes

  6. Microbes that produce antibiotics

  7. Range of activity • Narrow range: target one group of microbes • Broad range: target a wide group of different microbes • Which one is the best?

  8. Spectrum of activity

  9. Targets of antimicrobial drugs

  10. Targets of Cell Wall Synthesis

  11. How does penicillin work? • Inhibits formation of tetrapeptide side chains….which means…. • What happens if you put a cell in a solution with penicillin?

  12. Some drugs target protein synthesis

  13. Penicillin weakens the cell wall

  14. Beta-lactam ring common with penicillins and cephalosporins

  15. How organisms degrade penicillins

  16. Family of Penicillins • Natural penicillins- • Penicillin G and V • Penicillinase-resistant penicillins • Methicillin, Dicloxacillin • Broad-spectrum penicillins • Ampicillin, Amoxicillin • Extended-spectrum penicillins • Ticaricillin, Piperacillin • Penicillins plus beta-lactamase inhibitors • Augmentin (amoxicillin and clavulanic acid)

  17. Side chain varies for derivatives of penicillin

  18. Cephalosporins • Derived from fungus, Acremonium cephalosporium • Chemical structure makes them resistant to beta-lactamase, low affinity for penicillin binding proteins • Grouped into first, second, third, and fourth generation cephalosporins

  19. Vancomycin • Binds to the terminal amino acids of the peptide chain of NAM molecules, blocks peptidoglycan formation

  20. Antibiotics that inhibit protein synthesis

  21. Aminoglycosides • Bactericidal • Irreversibly bind to 30S ribosome, cause misreading of the mRNA • Transported into cells that actively respire (not effective against ananerobes, streptococci, enterococci) • Ex: streptomycin, gentamicin, tobramycin

  22. Tetracyclines • Bind reversibly to 30S, block attachment of the tRNA to ribosome • Actively transported into bacterial cells • Effective against gram positive and gram negative • Resistance: due to decrease in uptake or increase in excretion • Ex: Doxycycline

  23. Macrolides • Reversibly bind to the 50S, prevent continuation of protein synthesis • Drug of choice for patients allergic to penicillins • Not good for Enterobacteriaceae • Ex: Erythromycin, Azithromycin • Resistance: enzymes that alter drug, decreased uptake

  24. Oxazolidinones • Reversibly bind to the 50S subunit, interfere with initiation of protein synthesis • Used for treating gram positive infections resistant to Beta-lactam drugs and Vancomycin • Ex: Linezolid

  25. Antibiotics that inhibit nucleic acid synthesis • Fluoroquinolones • Inhibit topoisomerase • Rifamycins • Blocks prokaryotic RNA polymerase from initiating transcription

  26. Antibiotics that inhibit metabolic pathways • Sulfonamides • Trimethoprims

  27. Sulfonamides (sulfa drugs) • First synthetic drugs to treat microbial infections • Used to treat urinary tract infections (UTIs) • Combination of trimethoprim and sulfamethoxazole (TMP-SMZ) example of synergism

  28. Tests for microbial sensitivity • Kirby-Bauer (disk diffusion method) • We did this in lab • Determining the Minimum Inhibitory Concentration (MIC) • E test • easier way to determine the MIC

  29. Kirby-Bauer tests for sensitivity

  30. Determining the Minimum Inhibitory Concentration (MIC)

  31. E-test for MIC

  32. What resistance looks like…

  33. Mechanisms of Drug resistance • Destruction or inactivation of the drug • Prevention of penetration to target site • Alteration of target site (mutation) • Pumping of the drug out of the bacterial cell

  34. Emerging Antibiotic Resistance • Enterococci • Staphylococcus aureus • Steptococcus pneumoniae • Mycobacterium tuberculosis

  35. Targets of Viral drugs

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