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Antimicrobial Drugs

Delve into the world of antimicrobial drugs and how they combat diseases through selective toxicity. Learn about the mechanisms of antimicrobial action, modes of action, and antibiotic resistance. Explore the microbial sources of antibiotics and the spectrum of activity they offer. Discover the various inhibitors targeting cell wall synthesis, protein synthesis, plasma membrane, and nucleic acid synthesis. Uncover the roles of antiviral, antiprotozoan, and antihelminthic drugs in preventing infections. Dive into the importance of measuring antimicrobial sensitivity and understanding antibiotic resistance mechanisms. Join the fight against antimicrobial resistance for a brighter and healthier tomorrow.

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Antimicrobial Drugs

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  1. Antimicrobial Drugs Fading Miracle?

  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. PenicillinsFig 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 DrugsNucleoside and Nucleotide Analogs Figure 20.16a

  26. Analogs Block DNA Synthesis Figure 20.16b, c

  27. Antiviral DrugsEnzyme Inhibitors • Inhibit assembly • Indinavir (HIV) • Inhibit attachment • Zanamivir (Influenza) • Inhibit uncoating • Amantadine (Influenza)

  28. Antiviral DrugsEnzyme 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

  43. Multi-Drug Resistant TB

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

  45. Vancomycin Resistant Enterococci

  46. Vancomycin Use USA

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

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

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

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