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Antimicrobial Drugs

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Antimicrobial Drugs Fading Miracle? Ehrlich s Magic Bullets Fleming and Penicillin Chemotherapy The use of drugs to treat a disease Selective toxicity: A drug that ... – PowerPoint PPT presentation

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Title: Antimicrobial Drugs


1
Antimicrobial Drugs
  • Fading Miracle?

2
Ehrlichs 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 drug's 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
(No Transcript)
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
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