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
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

18. Antibacterial Antibiotics Inhibitors of Protein Synthesis
Streptogramins
Gram-positives
Binds 50S subunit, inhibits translation
Synercid
Oxazolidinones
Linezolid
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 Drugs Inhibition of Ergosterol Synthesis
Polyenes
Amphotericin B
Azoles
Miconazole
Triazoles
Allylamines
Figure 20.15

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

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

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

27. Antiviral Drugs Nucleoside and Nucleotide Analogs
Figure 20.16a

28. Antiviral Drugs Nucleoside and Nucleotide Analogs
Figure 20.16b, c

29. Antiviral Drugs Enzyme Inhibitors
Protease inhibitors
Indinavir
HIV
Inhibit attachment
Zanamivir
Influenza
Inhibit uncoating
Amantadine
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

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