1. Prof Dr Thamer Mutlag Jasim
Antimicrobial Drugs
Prof Dr Thamer Mutlag Jasim

2. Ehrlich’s Magic Bullets

3. Fleming and Penicillin

4. Chemotherapy The use of drugs to treat a disease
Selective toxicity: A drug that kills harmful microbes without damaging the host

5. Antibiotic/Antimicrobial
Antibiotic: Chemical produced by a microorganism that kills or inhibits the growth of another microorganism
Antimicrobial agent: Chemical that kills or inhibits the growth of microorganisms

6. Microbial Sources of Antibiotics

7. Antibiotic Spectrum of Activity
No antibiotic is effective against all microbes

8. Mechanisms of Antimicrobial Action
Bacteria have their own enzymes for
Cell wall formation
Protein synthesis
DNA replication
RNA synthesis
Synthesis of essential metabolites

9. Mechanisms of Antimicrobial Action
Viruses use host enzymes inside host cells
Fungi and protozoa have own eukaryotic enzymes
The more similar the pathogen and host enzymes, the more side effects the antimicrobials will have

10. Modes of Antimicrobial Action

11. Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis
Penicillin (over 50 compounds)
Share 4-sided ring (b lactam ring)
Natural penicillins
Narrow range of action
Susceptible to penicillinase (b lactamase)

12. Prokaryotic Cell Walls

13. Penicillins Fig 20.6
Figure 20.6

14. Penicillinase (b Lactamase)
Figure 20.8

15. Semisynthetic Penicillins
Penicilinase-resistant penicillins
Carbapenems: very broad spectrum
Monobactam: Gram negative
Extended-spectrum penicillins
Penicillins + -lactamase inhibitors

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

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

18. Other Inhibitors of Cell Wall Synthesis
Antibiotics effective against Mycobacteria: interfere with mycolic acid synthesis or incorporation
Isoniazid (INH)
Ethambutol

19. Inhibitors of Protein Synthesis
Broad spectrum, toxicity problems
Examples
Chloramphenicol (bone marrow)
Aminoglycosides: Streptomycin, neomycin, gentamycin (hearing, kidneys)
Tetracyclines (Rickettsias & Chlamydia; GI tract)
Macrolides: Erythromycin (gram +, used in children)

20. Injury to the Plasma Membrane
Polymyxin B (Gram negatives)
Topical
Combined with bacitracin and neomycin (broad spectrum) in over-the-counter preparation

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

22. Competitive Inhibitors
Sulfonamides (Sulfa drugs)
Inhibit folic acid synthesis
Broad spectrum
Figure 5.7

23. Antifungal Drugs Fungi are eukaryotes
Have unique sterols in their cell walls
Pathogenic fungi are often outside the body

24. Antiviral Drugs
Viruses are composed of nucleic acid, protein capsid, and host membrane containing virus proteins
Viruses live inside host cells and use many host enzymes
Some viruses have unique enzymes for DNA/RNA synthesis or protein cutting in virus assembly
Figure 20.16a

25. Antiviral Drugs Nucleoside and Nucleotide Analogs
Figure 20.16a

26. Analogs Block DNA Synthesis
Figure 20.16b, c

27. Antiviral Drugs Enzyme Inhibitors
Inhibit assembly
Indinavir (HIV)
Inhibit attachment
Zanamivir (Influenza)
Inhibit uncoating
Amantadine (Influenza)

28. Antiviral Drugs Enzyme Inhibitors
Interferons prevent spread of viruses to new cells (Viral hepatitis)
Natural products of the immune system in viral infections

29. Antiprotozoan Drugs Protozoa are eukaryotic cells
Many drugs are experimental and their mode of action is unknown

30. Antihelminthic Drugs
Helminths are macroscopic multicellular eukaryotic organisms: tapeworms, roundworms, pinworms, hookworms

31. Antihelminthic Drugs Prevent ATP generation (Tapeworms)
Alters membrane permeability (Flatworms)
Neuromuscular block (Intestinal roundworms)
Inhibits nutrient absorption (Intestinal roundworms)
Paralyzes worm (Intestinal roundworms)

32. Measuring Antimicrobial Sensitivity
E Test
MIC: Minimal inhibitory concentration

33. Measuring Antimicrobial Sensitivity: Disk Diffusion

34. Antibiotic Resistance
Figure 20.20

35. Antimicrobial Resistance
Relative or complete lack of effect of antimicrobial against a previously susceptible microbe
Increase in MIC

36. Mechanisms of Antibiotic Resistance
Enzymatic destruction of drug
Prevention of penetration of drug
Alteration of antibiotic or target site
Rapid ejection of the drug

37. Antibiotic Selection for Resistant Bacteria

38. What Factors Promote Antimicrobial Resistance?
Exposure to sub-optimal levels of antimicrobial
Exposure to microbes carrying resistance genes

39. Inappropriate Antimicrobial Use
Prescription not taken correctly
Antibiotics for viral infections
Antibiotics sold without medical supervision
Spread of resistant microbes in hospitals due to lack of hygiene

40. Inappropriate Antimicrobial Use
Lack of quality control in manufacture or outdated antimicrobial
Inadequate surveillance or defective susceptibility assays
Poverty or war
Use of antibiotics in foods

41. Antibiotics in Foods
Antibiotics are used in animal feeds and sprayed on plants to prevent infection and promote growth
Multi drug-resistant Salmonella typhi has been found in 4 states in 18 people who ate beef fed antibiotics

42. Consequences of Antimicrobial Resistance
Infections resistant to available antibiotics
Increased cost of treatment

44. Multi-Drug Resistant TB

45. MRSA “mer-sah” Methicillin-Resistant Staphylococcus aureus
Most frequent nosocomial (hospital-acquired) pathogen
Usually resistant to several other antibiotics

46. Vancomycin Resistant Enterococci

47. Vancomycin Use USA

48. Proposals to Combat Antimicrobial Resistance
Speed development of new antibiotics
Track resistance data nationwide
Restrict antimicrobial use
Direct observed dosing (TB)

49. Proposals to Combat Antimicrobial Resistance
Use more narrow spectrum antibiotics
Use antimicrobial cocktails

50. The Future of Chemotherapeutic Agents
Antimicrobial peptides
Broad spectrum antibiotics from plants and animals
Squalamine (sharks)
Protegrin (pigs)
Magainin (frogs)

51. The Future of Chemotherapeutic Agents
Antisense agents
Complementary DNA or peptide nucleic acids that binds to a pathogen's virulence gene(s) and prevents transcription