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Chapter 20

Chapter 20. Antimicrobial Drugs. Antimicrobial Drugs. Chemotherapy The use of drugs to treat a disease Antimicrobial drugs Interfere with the growth of microbes within a host Antibiotic Substance produced by a microbe that, in small amounts, inhibits another microbe

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Chapter 20

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  1. Chapter 20 Antimicrobial Drugs

  2. Antimicrobial Drugs • Chemotherapy The use of drugs to treat a disease • Antimicrobial drugs Interfere with the growth of microbes within a host • Antibiotic Substance produced by a microbe that, in small amounts, inhibits another microbe • Selective toxicity A drug that kills harmful microbes without damaging the host

  3. 1928 – Fleming discovered penicillin, produced by Penicillium. • 1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin. Figure 20.1

  4. Table 20.1

  5. Table 20.2

  6. The Action of Antimicrobial Drugs • Broad-spectrum • Superinfection • Bactericidal • Bacteriostatic

  7. The Action of Antimicrobial Drugs Figure 20.2

  8. The Action of Antimicrobial Drugs Figure 20.4

  9. Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Penicillin • Natural penicillins • Semisynthetic penicillins

  10. Penicillins Figure 20.6

  11. Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Penicillin • Penicilinase-resistant penicillins • Extended-spectrum penicillins • Penicillins + -lactamase inhibitors • Carbapenems • Monobactam

  12. Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Figure 20.8

  13. Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Cephalosporins • 2nd, 3rd, and 4th generations more effective against gram-negatives Figure 20.9

  14. Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Polypeptide antibiotics • Bacitracin • Topical application • Against gram-positives • Vancomycin • Glycopeptide • Important "last line" against antibiotic resistant S. aureus

  15. Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Antimycobacterium antibiotics • Isoniazid (INH) • Inhibits mycolic acid synthesis • Ethambutol • Inhibits incorporation of mycolic acid

  16. Antibacterial Antibiotics Inhibitors of Protein Synthesis • Chloramphenicol • Broad spectrum • Binds 50S subunit, inhibits peptide bond formation • Aminoglycosides • Streptomycin, neomycin, gentamycin • Broad spectrum • Changes shape of 30S subunit

  17. Antibacterial Antibiotics Inhibitors of Protein Synthesis • Tetracyclines • Broad spectrum • Interferes with tRNA attachment • Macrolides • Gram-positives • Binds 50S, prevents translocation • Erythromycin • Gram-positives • Binds 50S, prevents translocation

  18. Antibacterial Antibiotics Inhibitors of Protein Synthesis • Streptogramins • Gram-positives • Binds 50S subunit, inhibits translation • Synercid • Gram-positives • Binds 50S subunit, inhibits translation • Oxazolidinones • Linezolid • Gram-positives • Binds 50S subunit, prevents formation of 70S ribosome

  19. Antibacterial Antibiotics Injury to the Plasma Membrane • Polymyxin B • Topical • Combined with bacitracin and neomycin in over-the-counter preparation

  20. Antibacterial Antibiotics Inhibitors of Nucleic Acid Synthesis • Rifamycin • Inhibits RNA synthesis • Antituberculosis • Quinolones and fluoroquinolones • Ciprofloxacin • Inhibits DNA gyrase • Urinary tract infections

  21. Antibacterial Antibiotics Competitive Inhibitors • Sulfonamides (Sulfa drugs) • Inhibit folic acid synthesis • Broad spectrum Figure 5.7

  22. Figure 20.13

  23. Antifungal DrugsInhibition of Ergosterol Synthesis • Polyenes • Amphotericin B • Azoles • Miconazole • Triazoles • Allylamines Figure 20.15

  24. Antifungal DrugsInhibition of Cell Wall Synthesis • Echinocandins • Inhibit synthesis of -glucan • Cancidas is used against Candida and Pneumocystis

  25. Antifungal DrugsInhibition of Nucleic Acids • Flucytocine • Cytosine analog interferes with RNA synthesis • Pentamidine isethionate • Anti-Pneumocystis; may bind DNA

  26. Antifungal DrugsInhibition of Microtubules (Mitosis) • Griseofulvin • Used for superficial mycoses • Tolnaftate • Used for athlete's foot; action unknown

  27. Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16a

  28. Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16b, c

  29. Antiviral DrugsEnzyme Inhibitors • Protease inhibitors • Indinavir • HIV • Inhibit attachment • Zanamivir • Influenza • Inhibit uncoating • Amantadine • Influenza • Interferons prevent spread of viruses to new cells • Viral hepatitis

  30. Antiprotozoan Drugs • Chloroquine • Inhibits DNA synthesis • Malaria • Diiodohydroxyquin • Unknown • Amoeba • Metronidazole • Damages DNA • Entamoeba, Trichomonas

  31. Antihelminthic Drugs • Niclosamide • Prevents ATP generation • Tapeworms • Praziquantel • Alters membrane permeability • Flatworms • Pyantel pamoate • Neuromuscular block • Intestinal roundworms

  32. Antihelminthic Drugs • Mebendazole • Inhibits nutrient absorption • Intestinal roundworms • Ivermectin • Paralyzes worm • Intestinal roundworms

  33. Disk-Diffusion Test Figure 20.17

  34. E Test Figure 20.18

  35. MIC Minimal inhibitory concentration • MBC Minimal bactericidal concentration

  36. Broth Dilution Test Figure 20.19

  37. Figure 20.20

  38. Antibiotic Resistance • A variety of mutations can lead to antibiotic resistance. • Mechanisms of antibiotic resistance 1. Enzymatic destruction of drug 2. Prevention of penetration of drug 3. Alteration of drug's target site 4. Rapid ejection of the drug • Resistance genes are often on plasmids or transposons that can be transferred between bacteria.

  39. Antibiotic Resistance • Misuse of antibiotics selects for resistance mutants. Misuse includes: • Using outdated, weakened antibiotics • Using antibiotics for the common cold and other inappropriate conditions • Use of antibiotics in animal feed • Failure to complete the prescribed regimen • Using someone else's leftover prescription

  40. Effects of Combinations of Drugs • Synergism occurs when the effect of two drugs together is greater than the effect of either alone. • Antagonism occurs when the effect of two drugs together is less than the effect of either alone.

  41. Effects of Combinations of Drugs Figure 20.22

  42. The Future of Chemotherapeutic Agents • Antimicrobial peptides • Broad spectrum antibiotics from plants and animals • Squalamine (sharks) • Protegrin (pigs) • Magainin (frogs) • Antisense agents • Complementary DNA or peptide nucleic acids that binds to a pathogen's virulence gene(s) and prevents transcription

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