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WEL-COME

WEL-COME. DHANAJI NANA MAHAVIDYALAYA,FAIZPUR DEPARTMENT OF MICROBIOLOGY Antimicrobial Drugs Assi.Prof.Suvarna D.Patil. Ehrlich’s Magic Bullets. Fleming and Penicillin. Chemotherapy. The use of drugs to treat a disease

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WEL-COME

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  1. WEL-COME

  2. DHANAJI NANA MAHAVIDYALAYA,FAIZPURDEPARTMENT OF MICROBIOLOGYAntimicrobial DrugsAssi.Prof.SuvarnaD.Patil

  3. Ehrlich’s Magic Bullets

  4. Fleming and Penicillin

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

  6. 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

  7. Microbial Sources of Antibiotics

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

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

  10. 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

  11. Modes of Antimicrobial Action

  12. 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)

  13. Prokaryotic Cell Walls

  14. PenicillinsFig 20.6 Figure 20.6

  15. Penicillinase (b Lactamase) Figure 20.8

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

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

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

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

  20. 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)

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

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

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

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

  25. 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

  26. Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16a

  27. Analogs Block DNA Synthesis Figure 20.16b, c

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

  29. Antiviral DrugsEnzyme Inhibitors • Interferons prevent spread of viruses to new cells (Viral hepatitis) • Natural products of the immune system in viral infections

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

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

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

  33. Measuring Antimicrobial Sensitivity • E Test • MIC: Minimal inhibitory concentration

  34. Measuring Antimicrobial Sensitivity: Disk Diffusion

  35. Antibiotic Resistance Figure 20.20

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

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

  38. Antibiotic Selection for Resistant Bacteria

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

  40. 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

  41. 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

  42. 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

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

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

  45. 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

  46. THANK YOU….

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