Antibiotics

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Antibiotics

  1. 1. Antimicrobial Drugs Fading Miracle?
  2. 2. Ehrlich’s Magic Bullets
  3. 3. Fleming and Penicillin
  4. 4. Chemotherapy • The use of drugs to treat a disease • Selective toxicity: A drug that kills harmful microbes without damaging the host
  5. 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. 6. Microbial Sources of Antibiotics
  7. 7. Antibiotic Spectrum of Activity • No antibiotic is effective against all microbes
  8. 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. 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. 10. Modes of Antimicrobial Action
  11. 11. • Penicillin (over 50 compounds) –Share 4-sided ring (β lactam ring) • Natural penicillins •Narrow range of action •Susceptible to penicillinase (β lactamase) Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis
  12. 12. Prokaryotic Cell Walls
  13. 13. Penicillins Figure 20.6
  14. 14. Penicillinase (β Lactamase) Figure 20.8
  15. 15. • Penicilinase-resistant penicillins •Carbapenems: very broad spectrum •Monobactam: Gram negative • Extended-spectrum penicillins • Penicillins + β-lactamase inhibitors Semisynthetic Penicillins
  16. 16. • Cephalosporins –2nd , 3rd , and 4th generations more effective against gram- negatives Other Inhibitors of Cell Wall Synthesis Figure 20.9
  17. 17. • Polypeptide antibiotics –Bacitracin •Topical application •Against gram-positives –Vancomycin •Glycopeptide •Important "last line" against antibiotic resistant S. aureus Other Inhibitors of Cell Wall Synthesis
  18. 18. Other Inhibitors of Cell Wall Synthesis • Antibiotics effective against Mycobacteria: interfere with mycolic acid synthesis or incorporation –Isoniazid (INH) –Ethambutol
  19. 19. • 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) Inhibitors of Protein Synthesis
  20. 20. • Polymyxin B (Gram negatives) –Topical –Combined with bacitracin and neomycin (broad spectrum) in over- the-counter preparation Injury to the Plasma Membrane
  21. 21. • Rifamycin –Inhibits RNA synthesis –Antituberculosis • Quinolones and fluoroquinolones –Ciprofloxacin –Inhibits DNA gyrase –Urinary tract infections Inhibitors of Nucleic Acid Synthesis
  22. 22. –Sulfonamides (Sulfa drugs) •Inhibit folic acid synthesis •Broad spectrum Competitive Inhibitors Figure 5.7
  23. 23. Antifungal Drugs • Fungi are eukaryotes • Have unique sterols in their cell walls • Pathogenic fungi are often outside the body
  24. 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. 25. Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.16a
  26. 26. Figure 20.16b, c Analogs Block DNA Synthesis
  27. 27. • Inhibit assembly –Indinavir (HIV) • Inhibit attachment –Zanamivir (Influenza) • Inhibit uncoating –Amantadine (Influenza) Antiviral Drugs Enzyme Inhibitors
  28. 28. • Interferons prevent spread of viruses to new cells (Viral hepatitis) • Natural products of the immune system in viral infections Antiviral Drugs Enzyme Inhibitors
  29. 29. Antiprotozoan Drugs • Protozoa are eukaryotic cells • Many drugs are experimental and their mode of action is unknown
  30. 30. Antihelminthic Drugs • Helminths are macroscopic multicellular eukaryotic organisms: tapeworms, roundworms, pinworms, hookworms
  31. 31. • Prevent ATP generation (Tapeworms) • Alters membrane permeability (Flatworms) • Neuromuscular block (Intestinal roundworms) • Inhibits nutrient absorption (Intestinal roundworms) • Paralyzes worm (Intestinal roundworms) Antihelminthic Drugs
  32. 32. Measuring Antimicrobial Sensitivity • E Test • MIC: Minimal inhibitory concentration
  33. 33. Measuring Antimicrobial Sensitivity: Disk Diffusion
  34. 34. Figure 20.20 Antibiotic Resistance
  35. 35. Antimicrobial Resistance • Relative or complete lack of effect of antimicrobial against a previously susceptible microbe • Increase in MIC
  36. 36. • Enzymatic destruction of drug • Prevention of penetration of drug • Alteration of drug's target site • Rapid ejection of the drug Mechanisms of Antibiotic Resistance
  37. 37. Antibiotic Selection for Resistant Bacteria
  38. 38. What Factors Promote Antimicrobial Resistance? • Exposure to sub-optimal levels of antimicrobial • Exposure to microbes carrying resistance genes
  39. 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. 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. 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. 42. Consequences of Antimicrobial Resistance • Infections resistant to available antibiotics • Increased cost of treatment
  43. 43. Multi-Drug Resistant TB
  44. 44. MRSA “mer-sah” • Methicillin-Resistant Staphylococcus aureus • Most frequent nosocomial (hospital-acquired) pathogen • Usually resistant to several other antibiotics
  45. 45. Vancomycin Resistant Enterococci
  46. 46. Vancomycin Use USA
  47. 47. Proposals to Combat Antimicrobial Resistance • Speed development of new antibiotics • Track resistance data nationwide • Restrict antimicrobial use • Direct observed dosing (TB)
  48. 48. Proposals to Combat Antimicrobial Resistance • Use more narrow spectrum antibiotics • Use antimicrobial cocktails
  49. 49. • Antimicrobial peptides –Broad spectrum antibiotics from plants and animals •Squalamine (sharks) •Protegrin (pigs) •Magainin (frogs) The Future of Chemotherapeutic Agents
  50. 50. • Antisense agents –Complementary DNA or peptide nucleic acids that binds to a pathogen's virulence gene(s) and prevents transcription The Future of Chemotherapeutic Agents

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